Student Profiles Archive - URSP 2011-2012
Here you will find information about past and present students funded through scholarships administered by the Undergraduate Research Center - Sciences. We are proud of the achievements of our research scholars.
Please click on the program year to get information about the supported students, their mentors and their research projects.
| Mr. Abhimanyu Amarnani
Mr. Abhimanyu Amarnani
Mentor: Dr. Ivan Lopez
Title: Protective Mechanism(s) of Mild Carbon Monoxide (CO) Exposure in Systemic lupus Erythematosus Model (MRL/lpr) Mice Cerebella.
Abhimanyu Amarnani is a 3rd year undergraduate student majoring in Psychobiology. Under the guidance of Dr. Ivan A. Lopez he has been conducting research at UCLA since the beginning of his second year.
Heme oxygenase (HO)-1 serves as a protective enzyme by virtue of its anti-inflammatory, anti-apoptotic and anti-proliferative actions. These findings have also been supported by the fact that HO-1 deficient mice have a chronic inflammatory state that progresses with age and the only human case of a patient that lacks HO-1 enzymatic activity died of a chronic inflammatory syndrome. Furthermore, there is a growing body of evidence that suggests that HO-1 functions as a ‘therapeutic funnel’ by mediating the beneficial effects attributed to other molecules, such as interleukin-10 (IL-10), inducible nitric oxide synthase (NOS2; iNOS) and prostaglandins.
Heme oxygenase-1 functions by breaking down heme into three products: carbon monoxide (CO), biliverdin and free iron. Many of the beneficial effects of HO-1 come from CO and this is the focus of Abhimanyu’s research. CO treatment has already been shown to be very beneficial in preventing rejection of graft during transplants and also ameliorates the severity of ischemia reperfusion injury. As a bridge from previous research, he focuses on the mice model MRL/lpr, which has a chronic condition similar to Systemic Lupus Erythematosus. His work studies the protective mechanisms of CO on the cerebellum of these mice. Lupus is an autoimmune disease condition that is defined in part by its chronic inflammatory state. Abhimanyu is currently focusing on the cerebellum because neural symptoms contribute to a significant percentage of morbidity and mortality in patients with lupus.
He hopes to use the knowledge and expertise he has gained from his research experience after his undergraduate career as he aspires to earn a M.D./PhD degree. He would like to thank his encouraging mentor, Dr. Ivan A. Lopez, for all the support and guidance he has given him over the years and would also like to express his utmost gratitude to the Gottlieb Family for their generous contribution to undergraduate research. Finally, Abhimanyu would like to thank the URC - Sciences office for organizing an excellent venue to help students at UCLA move one step closer to their research dreams.
| Mr. Armin Arshi
Mr. Armin Arshi
Mentor: Dr. Atsushi Nakano
Title: Applications of Biomolecular Scaffolds and Matrix Elasticity in Cardiac Tissue Engineering
Armin Arshi is currently a fourth year undergraduate Bioengineering major and has been conducting research in the lab of Dr. Atsushi Nakano since February 2009 studying cardiac development.
Current scientific knowledge suggests that cell behavior and morphology is influenced by a combination of intercellular interactions, soluble molecular factors, and insoluble cues. Though difficult to adequately recapitulate in vitro, cell microenvironments appear to be important in stem cell lineage specification. Previous studies suggest that the phenotype, both in morphology and gene expression, of mesenchymal stem cells is extremely sensitive to tissue-level elasticity. With varied substrate stiffness, cells were cultured down a specific lineage trajectory. Soft matrices mimicking brain tissue and rigid matrices resembling collageneous bone, for example, were neurogenic and osteogenic, respectively. The formation of focal-adhesion and cytoskeletal structures is known to influence the wide variation in matrix stiffness for differentiated cells. This mechanism is believed to involve nonmuscle myosin II, whose inhibition completely blocks elasticity-driven lineage specification.
Using carefully engineered biomolecular scaffolds, Armin’s group intends to further this hypothesis and alter pre-deterministic mouse embryonic stem cells in vitro to “push” them down the cardiomyocyte lineage trajectory. By culturing cells in microenvironments of intermediate stiffness, they hope to find a greater yield of cardiac troponin T (cTnT) expression and visibly “beating” cardiomyocytes as compared to standard in vitro tissue culture methods. In addition to delineating the effects of the physical microenvironment on cardiogenesis and other developmental processes, these findings could also have implications in furthering stem cell therapy, by manipulating organotypic explant culture and other means of controlled tissue engineering.
After graduation, Armin intends to pursue a medical degree and subsequent research training in preparation for a career in academic medicine and biomedical research. He would like to thank the Oppenheimer Foundation and the entire Nakano lab for supporting his research endeavors, both past and present.
| Mr. Alvaro Assuncao
Mr. Alvaro Assuncao
Mentor: Dr. Paul Mischel
Title: On-chip Cell Sorting Using DNA-encoded Antibody Library (DEAL).
Glioblastoma (GBM) is the most common type of brain tumor and one of the most lethal of all cancers. GBM is also extremely resistant to chemo- and radio-therapy and for this reason, it is important that new treatment approaches be developed. Dr. Paul Mischel’s laboratory works on the novel concept of personalized therapy, a treatment which focuses on defining the characteristics of the patient’s cancer cells in order to use specific medications to target the cancer-causing DNA alterations. Since cancer tissues are composed of a mixture of cells with different types of modifications, identifying the specific alterations that make up a patient’s biopsy sample poses a really hard task. Alvaro’s project involves the recently developed technology called DNA Encoded Antibody Library (DEAL), which is used to more efficiently capture and sort cells by their alteration type. His project uses the DEAL technology to investigate the composition of patients’ biopsy as well as autopsy samples. This technology enables him to separate the different types of cells based on their characteristic surface proteins. After sorting the cells out of the mixture of cells present in the patient’s sample, Alvaro is able to perform a series of procedures to extract the genetic material (DNA) from each of these cell types. Once he has obtained the DNA from the patient’s cancer cells, he is able to identify their genetic mutations through comparing this DNA composition to the DNA of a normal individual.
The significance of this project lies in the fact that upon finding the specific altered genes, which lead to the development and growth of cancer cells, one can more effectively use treatment approaches that counter balance the abnormal expression of proteins. In other words, mutation type-specific drugs would be administered in the treatment of glioblastoma patients in order to provide a more personalized therapy based on the characteristics of patients’ cancer cells.
Alvaro would like to thank Drs. Paul Mischel and Beatrice Gini, his postdoctoral mentor, for their support.
| Mr. Hayk Barseghyan
Mr. Hayk Barseghyan
Mentor: Dr. Eric Vilain
Title: Sexual Partner Preference of Klinefelter (XXY) and Normal (XY) Male Mice Towards a Female Mouse
Hayk Barseghyan is a fourth year undergraduate student who is double majoring in Integrative Biology and Physiology and Russian Language and Literature. With an interest in human genetics and neuroscience Hayk has been working in Dr. Vilains’ lab since May of 2010 under guidance of graduate students Tuck Ngun and Negar Ghahramani.
In his project Hayk will be addressing the question of sexual partner preference of XXY-Sry male mice (which resemble the genotype of human Klinefelter patients) and XY-Sry (control) towards a female mouse. It is suspected that having different number of sex determining chromosomes may affect or even control sexual partner preference. The results might demonstrate the role of sex chromosomes in regulation of sexual partner preference and perhaps show that the sexual behavior of the animal is dependent not only on gonadal secretion but also on sex chromosomes. In addition, the significance of this work might be the determination of neural correlations of partner preference.
Hayk will be graduating on June 2012 and plans taking his career towards medicine. Hayk also, sincerely thanks the Wasserman Family for providing financial assistance, URSP program for making this possible and his lab mentors for intellectual guidance and support that make his experience at UCLA better than ever.
| Ms. Mariam Barseghyan
Ms. Mariam Barseghyan
Mentor: Dr. Arthur Arnold
Title: Sex Differences in Hypothalamic Peptide and Protein Levels Involved in Increased Feeding Habits/Obesity of XX vs. XY Mice
Mariam Barseghyan is a fourth year undergraduate student majoring in Physiological Science and Russian Language and Literature. She is exceedingly interested in investigating the causes leading to differential adiposity patterns in males versus females. Excessive adiposity may lead to obesity in both genders which in turn is the leading cause for such cardiovascular diseases as atherosclerosis. Clinical observations show a clear distinction between the expression of cardiovascular diseases and other obesity related conditions in males versus females.
Dr. Arnold’s laboratory has identified increased feeding habits of XX males and females relative to XY male and female mice. Thus, differential eating habits that depend on a chromosomal type may constitute for the observed adiposity variations between the two genders. Currently, Mariam is involved in a project under the supervision of Dr. Xuqi Chen and Dr. Arthur P. Arnold, where she tests to determine the influence of sex chromosomes on the pathways involved in regulation of feeding process. She is working on identifying whether increased eating habits and thus the greater adiposity of XX mice, relative to XY, is correlated with the changes in the protein / peptide levels, or the number of neurons expressing these proteins or peptides (AgRP, NPY, POMC, CART, and CNTF) in the hypothalamus.
Mariam aspires to obtain a dual M.D./PhD degree in the near future. She is convinced that this will help her in a better understanding, diagnosis and treatment of patients. Mariam would like to express her sincere gratitude to Dr. Arnold and Dr. Chen for their support and the opportunity to experience what it is really like to be an investigator. She also wishes to thank the URC - Sciences office for all their hard work in assisting students along their academic journey.
| Mr. Randy Chang
Mr. Randy Chang
Mentor: Dr. Patrick Harran
Title: New Strategies for the Synthesis of Complex Prodigiosin Alkaloids
Randy Chang is a fourth-year undergraduate student majoring in Psychobiology at UCLA. Under the mentorship of Dr. Patrick Harran and Dr. Jim Frederich, he has been conducting research since the beginning of his third year. His research focuses on the total synthesis of the natural product Roseophilin using a novel photo-induced electron transfer macrocyclization while probing its potential as a regulator of cell apoptosis in relation to cancer.
In cancer cells, the natural process of programmed cell death, apoptosis, is disrupted by many factors. One novel approach to cancer therapy involves acting on anti-apoptotic Bcl-2 proteins that inhibit the Bak and Bax proteins, two pro-apoptic factors located within the outer mitochondrial membrane. Cancer cells can overexpress Bcl-2, resulting in uncontrolled cell proliferation. Since Bak and Bax bind to Bcl-2 at what is called the BH3 binding domain, it is believed that small molecules which bind to this same site on Bcl-2 can stop key protein-protein interactions and restore the pro-apoptotic function of Bak and Bax as well as natural cell death. Currently in clinical trials, Obatoclax is believed to act on Bcl-2 to restore apoptosis; Randy believes that Roseophilin acts similarly and can more fully bind to the BH3 domain. The two compounds possess a carbon structure analogous to prodigiosin, a secondary metabolite of the bacterium Serratia marcescens. However, Roseophilin also harbors an ansa bridge, a long hydrocarbon loop that he believes will be able to bind more effectively to the hydrophobic portion of the BH3 site. Thus, Roseophilin, can be viewed as an elaborated structural analog of Obatoclax, may offer a stronger interaction with the BH3 domain, and can potentially lead to a more efficient drug for cancer therapies.
| Mr. Stephen Chang
Mr. Stephen Chang
Mentor: Dr. Albert Lai
Title: Understanding the Mechanism of Methylation of MGMT Promoters in Glioblastoma Cell Lines Using Episome Constructs.
Stephen Chang is a third year Neuroscience major. He has been working in Dr. Lai’s lab since Spring 2011 where he has contributed to studies concerned with improving therapies for malignant gliomas. Currently, Stephen’s work is on understanding the mechanisms involved in allowing patients to respond more effectively to radiation and chemical treatments.
Gliomas are a form of brain tumor that affects over 20,000 new patients in the United States each year and the survival rate for gliomas, especially glioblastomas (GBM), are severely low. Current radiation and chemical therapies are not entirely effective in treating glioma patients. Studies have shown, however, that when certain genes such as MGMT are methylated, glioma patients have an increased sensitivity towards these standard treatments and their survival rates increase. Stephen’s research focuses on understanding this methylation process that occurs in MGMT by inserting episomes into varying glioblastoma cell lines and analyzing the cell’s response to an exogenous MGMT promoter that can be methylated or unmethylated. Through these experiments, information can be collected on the methylation system present in glioblastoma cells. Once this is understood, it can be manipulated to ultimately allow glioma patients to have specific genes methylated or unmethylated to provide the optimal conditions for treatments to be effective and consequently allow an increased survival rate in patients.
Stephen would like to thank Dr. Albert Lai for the opportunity to conduct research in his laboratory and all members of the laboratory for their ongoing support. Stephen would also like to sincerely thank the Wasserman family for their generous funding, recognition, and support of his research.
| Ms. Iris Chen
Ms. Iris Chen
Mentor: Dr. Yibin Wang
Title: Long Non-Coding RNA in Hypertrophy and Heart Failure
Iris Chen is a third-year undergraduate student majoring in Psychobiology. Since spring quarter of 2011, she has been part of Dr. Yibin Wang's lab, which investigates the molecular basis of stress induced cardiomyopathy. Having studied the variability of heart failure pathogenesis via echocardiography previously, she is now taking a more microbiological approach with Dr. Zhihua Wang, focusing on long non-coding RNAs and understanding their functions with respect to hypertrophy and heart failure.
Chronic heart failure (CHF) affects 20 percent of the global population, causing high socioeconomic costs in its treatment. Its onset is induced by a compensatory response from the sympathetic nervous system and neurohormonal pathways, which increases the rate and intensity of heart contraction to sustain cardiac output. Chronic excessive activation of the sympathetic system, however, results in heart failure. The pathogenesis of heart failure is further complicated by the influence of various environmental and genetic factors, rendering the limited therapeutics available ineffective for a significant portion of CHF patients. Iris' research project implements a clinical purpose – by understanding the different genetic contributions to the variability of heart responses, the goal is to personalize medicine according to the patient’s genetic background.
Long non-coding RNAs have been shown to partake in biological activities, but the functions of the majority remain unknown, especially in the context of heart failure. Based on the previous studies, Iris specifies several long non-coding RNA candidates (C11-108m, C1-137m, and C2-118m) to investigate their impact on cell size and cell death. After validating the expression of these RNA in hypertrophy and heart failure models using Real-time PCR, she will clone the long non-coding RNA into the Adeno-virus and transfect neonatal rattus ventricular myocytes. Furthermore, she will inhibit these long non-coding RNAs using siRNA or antisense RNA to comprehend the signaling pathways underlying long non-coding RNA regulated heart function.
After graduating, Iris hopes to continue her education and research in an MD/PhD program. She would like to thank Dr. Yibin Wang and Dr. Zhihua Wang for their continued guidance and encouragement. Iris is also extremely grateful to Wasserman family for their generous contribution to her research.
| Ms. Vicky Chiang
Ms. Vicky Chiang
Mentor: Dr. Zhefeng Guo
Title: Structural Characterization of Ure2 Yeast Prion Protein
Vicky Chiang is a fourth year Biochemistry major. She has been working in Dr. Zhefeng Guo’s lab for the past two years. Her current research project focuses on characterizing the structural details of Ure2 prion protein using electron paramagnetic resonance (EPR) spectroscopy.
Prions are infectious agents composed of mis-folded proteins. They are responsible for a variety of fatal and incurable mammalian neurodegenerative diseases such as Creutzfeldt-Jakob’s in humans, mad-cow disease in cattle, and scrapie in sheep. Fungal prions, such as Ure2 and Sup35 in Saccharomyces cerevisiae, have been used as models for prion disease studies because they share similar properties to their mammalian counterparts. Sup35 has been known to aggregate into two different stable fibril structures at different temperatures, and transfection of the fibrils back into fungi results in differing prion strains. This suggests that fibril structure may be the basis of the prion strain phenomenon. However, it is unknown whether this occurs in Ure2 prions as well. Vicky’s project aims to elucidate whether Ure2 forms differing stable structures at differing temperatures, and to investigate the structural details of Ure2 using EPR spectroscopy. The structure of the Ure2 prion domain is poorly characterized, and EPR data would provide residue-specific details of Ure2 prion protein. Understanding fungal prion structure could lead to a better understanding of prion properties and lead to the development of structure-based drug design.
After graduation, Vicky intends to attend medical school. She would like to thank Dr. Guo and everyone at the Guo lab for their support and guidance, and for giving her this opportunity to do undergraduate research at UCLA.
| Mr. Eric Choi
Mr. Eric Choi
Mentor: Dr. Benhur Lee
Title: A Dually Inducible Cell Line for Analysis of Nipah Virus Membrane Fusion
Eric Choi is a 4th year Microbiology, Immunology, and Molecular Genetics major who is also pursuing a minor in Biomedical Research. He has been conducting research since his freshman year in Dr. Benhur Lee’s laboratory with the help of Hector Aguilar (Ph.D.) and Kelechi Chikere (Ph.D. Candidate). The Lee lab studies mechanisms of viral entry and membrane fusion of HIV and Nipah virus (NiV) with a focus on viral envelope and cell surface receptor interactions.
Nipah virus is an emerging zoonotic paramyxovirus that can cause encephalitis and respiratory diseases with a mortality rate of up to 72%. NiV utilizes the attachment (G) and fusion (F) glycoproteins for virus-cell membrane fusion. Expressing these viral proteins on the surfaces of mammalian cells allows the study of the NiV fusion mechanism without interacting directly with the actual deadly virus. Eric is currently generating a cell line that uses two separate inducible expression systems to allow the quantitative expression of NiV-G and NiV-F on the cell surface. Using these cells, Eric hopes to further elucidate steps in the NiV-G/F triggering and fusion mechanism. Understanding of the Nipah virus-cell membrane fusion mechanism can hopefully lead to future therapeutic treatments of not only Nipah virus but other paramyxoviruses including Human parainfluenza viruses, Measles virus, Mumps virus, and Newcastle disease virus.
Eric plans to graduate in the Spring of 2012 and attempt to get a MD/PhD. He would like to thank Hector for the many years of guidance and Benhur for the opportunity to learn in his lab. He would also like to thank Kelechi and Shannon for replacing past lab members both as mentors and as friends. Finally, Eric would like to thank the Wasserman family and Mr. Green for their generous support.
| Ms. Cassandra Coleman
Ms. Cassandra Coleman
Mentor: Dr. Anil Bhushan
Title: Identification and Characterization of Open Chromatin Regulatory Regions in Beta and Liver Cells
Cassie Coleman is a fourth year Molecular, Cell, and Developmental Biology major and French and Francophone Studies minor. She has been working in the Bhushan lab since March 2011. Under the guidance of Senta Georgia and Anil Bhushan, she is studying the chromatin confirmation around regulatory elements important in the expression of lineage determination genes.
The Bhushan lab seeks to understand mechanisms that define beta cell identity in an effort to generate beta cells from other cell type via cell fate conversion. Recent studies from the Bhushan lab indicate that cellular identity is not fixed, opening the possibility that other cell types may be able to be converted into beta cells. However, the factors and regulatory elements that dictate the expression of beta cell identity have not been identified.
Cassie aims to address the gap in knowledge by identifying regulatory elements encoded in the DNA that dictate the expression of genes that define cellular identity. Recent studies have indicated clusters of open regulatory elements (COREs) exist in intergenic regions and might have single-gene regulatory function. She will analyze open chromatin on a genome-wide scale in beta and liver cell lines in order to identify differences in chromatin state that may be linked to cellular identity. Ultimately, this knowledge would be used to determine if these elements could be exploited to convert liver cells into beta.
Upon graduating from UCLA, Cassie plans further her education by pursuing a career in health and medicine, obtaining concurrent medical and business degrees. She would like to extend her gratitude to the Bhushan Lab, especially Dr. Anil Bhushan and Dr. Senta Georgia, for their continuous guidance, support, and patience. She would also like to thank the Wasserman Family and the URSP program for their generous endowment and contribution to the academic success of UCLA students.
| Ms. Tamara Cutler
Ms. Tamara Cutler
Mentor: Dr. Christopher Colwell
Title: Autonomic Nervous System Regulation of Circadian Rhythms in Cardiac Function
Tamara Cutler is a senior undergraduate student double-majoring in Neuroscience and Molecular, Cellular and Integrative Physiology. She is working in Professor Chris Colwell’s lab studying the neurobiology and physiology of circadian rhythms. Tamara is currently investigating the regulation of circadian rhythms in cardiac muscle by the autonomic nervous system.
According to the American Heart Association, cardiovascular disease is the leading cause of death in the United States. Pathological cardiovascular events such as myocardial infarctions and arrhythmias, are clustered in the morning, suggesting involvement of the circadian system. Disruptions in the circadian system, such as shift work, are associated with increased incidence of cardiovascular disease and mortality.
The mechanism by which the body’s master clock, the suprachiasmatic nucleus (SCN), regulates circadian rhythms in cardiac tissue is not known but one prominent candidate for mediation of the SCN’s timely messages to cardiac tissue is the autonomic nervous system.
Tamara’s research project examines the effects of the application of autonomic peptides and neurotransmitters on cardiac tissue explants from Per2::Luc mice.
The effects of these autonomic signaling molecules on cardiomyocyte molecular clocks can be observed in tissues from knock-in mice bearing the Per2::Luc gene which combines the promoter of the clock gene, Per2, with luciferase, the gene for a bioluminescence producing enzyme from the firefly.
Properly timed application of acetylcholine, VIP, and norepinephrine analogues to explants is expected to improve measures of circadian rhythmicity in bioluminescence whereas inappropriately timed application is expected to degrade cardiomyocyte circadian rhythms. Of particular interest are interventions that may rescue circadian parameters of a degenerate rhythm in explants.
Tamara plans to obtain advanced degrees in medicine and research in preparation for a career in translational research. Tamara would like to thank her mentor, Professor Chris Colwell, and the entire lab for all they have contributed to her scientific training. She would also like to express her gratitude to the Gottlieb Estate for its generous support and to all the members of the URC - Sciences faculty and staff for their work supporting undergraduate researchers.
| Ms. Liane Dallalzadeh
Ms. Liane Dallalzadeh
Mentor: Dr. Kelsey Martin
Title: Interaction of miRNA124 on Localized GluA2 Translation and Functional Fole in Synaptic Plasticity in Primary Mouse Hippocampal Neurons
Liane Dallalzadeh is a third-year Neuroscience major and Public Health minor working under the mentorship of Victoria Ho in the laboratory of Dr. Kelsey Martin. The Martin lab is interested in how neurons restrict gene expression to a subset of synapses, and focuses on the role of localized messenger RNA (mRNA) transcripts and their regulated translation. Recent studies from the lab and others have revealed that a subset of mRNAs is present in distal subcellular regions. Liane’s project focuses on GluA2, a subunit of the AMPA-type glutamate receptor (AMPARs), and its interaction with microRNA-124 (miR-124). Liane joined the lab in March 2010 and will be completing an honors thesis at the end of this year. After graduation, she plans to attend medical school.
Neurons are able to modify the strength of their synaptic connections in response to the environment through a process called synaptic plasticity. Changes in synaptic strength contribute to an array of cognitive processes, including memory storage. Long-lasting forms of synaptic plasticity require new protein synthesis and can occur in a synapse-specific manner. AMPARs play a central role in synaptic plasticity, since the levels of AMPARs at a synapse determine its strength. Translation of localized mRNAs can be regulated by miRNAs, which bind to the 3’ untranslated regions of mRNAs to inhibit gene expression. The miR-124 target site is highly conserved within GluA2. Fluorescence in situ hybridization (FISH) will be used to visualize both GluA2 mRNA and miR-124 localization within primary mouse hippocampal neurons. Overexpression/knockdown studies will determine if miR-124 regulates translation of GluA2. A functional assay will also be performed to determine changes in synaptic strength as a result of changes in GluA2 levels.
Liane would like to thank the Undergraduate Research Scholars Program, Martin Lab, and the Oppenheimer Foundation for their generous support and continual guidance.
| Mr. Thomas Darlington
Mr. Thomas Darlington
Mentor: Dr. Jianwei Miao
Funding: Norton Rodman
Title: Three-dimensional Real-time Imaging of Gliding Motility in Apicomplexan Parasites Using 4D Dark Field Microscopy
Tom Darlington is a fourth year undergraduate student majoring in Physics. He began participating in research with the Coherent Imaging Group under Prof. John Miao in October of 2010. In the course of working in Prof. Miao’s group Tom has developed a strong interest in imaging techniques and processing, and plans to go onto graduate school in pursuit of a PhD in Physics.
Life is four dimensional. In order to fully understand biological samples, scientific methods must evolve to study all three spatial dimensions with time. We have developed a novel fast 4D imaging system, capable of capturing 3D images of living biological samples with a time resolution of 50 ~ 100 volumes per second. We have been applying this method the study of the Apicomplexan parasites Neospora Caninum, a close relative of Toxoplasma Gondii (responsible for disease in infants and immuno-compromised individuals) and Plasmodium falciparum (the causitivie agent in malaria). Using this method we have been able to capture the motility of Toxoplasma in 3D, with unprecedented time resolution. With this method we aim to uncover new details of the parasites’ motility and its invasion mechanism.
Tom would like to express his thanks to Prof. Miao for giving him this opportunity, and Jose Rodriguez for immense help and guidance in implementing this project.
| Mr. Debobrato Das
Mr. Debobrato Das
Mentor: Dr. Benjamin Wu
Title: Investigation of Biomimetic Calcium Apatite Nanoparticle Delivery Systems for Non-viral Gene Transfection Using MC3T3 Mouse Model
Debobrato Das is a fourth year undergraduate student majoring in Bioengineering. He has been working at the tissue engineering and biomaterials laboratory of Dr. Benjamin Wu since fall 2009 and is currently applying to graduate school with plans to pursue a career in regenerative medicine.
Current methods for gene delivery utilize nanomedicines such as liposomes and viral vectors that may produce in vivo toxicity, immunogenicity, mutagenesis, or carcinogenicity. Furthermore, a low efficacy of gene-capsule internalization across cell plasma membrane followed by inadequate release and weak intracellular stability of nucleic acids are some of the many challenges involved in gene delivery. Our approach on maximizing transfection efficiency while minimizing adverse host response capitalizes on the favorable biocompatible and biodegradable properties of calcium phosphate nanoparticles. Recent studies have shown that these inorganic particles may enhance nuclear uptake of DNA due to various calcium dependent cellular trafficking pathways. In general, biomimetic apatites constructed in vitro from simulated body fluids (SBF) endorses an increase in vivo bioactivity, decrease in fibrotic encapsulation and promotes cellular differentiation of bone marrow stromal cells. Thus, nanofabricated SBF apatite capsules fused with GAPDH siRNA, are administered to MC3T3 cells, a strain of tissue cultured cells widely used as model systems for bone biology, to assess GAPDH expression and consequent transfection effectiveness. Preliminary results have shown a significant “knock-down” of GAPDH expression in cells cultured with these apatite nanoparticles while consistently producing a less cytotoxic effect than traditional tranfection reagents such as Lipofectamine®.
Debobrato is extremely grateful to Dr. Benjamin Wu, Eric Tsang, and the entire Wu Lab for the valuable mentorship and support he has received throughout his time in the lab. He would also like to thank the Wasserman family for sponsoring him and UCLA URC - Sciences for their contribution to his undergraduate research.
| Mr. Sai Devana
Mr. Sai Devana
Mentor: Dr. Dwayne Simmons
Title: The Role of Oncomodulin in the Functionality of Outer Hair Cells within the Cochlea.
Sai Devana is currently a 3rd year undergraduate majoring in Molecular Cell and Biology. He has a strong passion for studies involving auditory function which led him to join the lab of Dr. Dwayne Simmons.
Age-related hearing loss or presbyacusis, affects about 1/3rd of adults over the age of 65. Calcium-sensitive pathways involving the calcium binding protein oncomodulin (Ocm) may play a role in progressive hearing loss. Sai’s project involves studying the function of Ocm in the outer hair cell of the inner ear and testing its effects on cell motility and functionality. He will be testing the hypothesize that Ocm modulates intracellular calcium [Ca2+]i levels in outer hair cells of the inner ear by acting as a buffer. By regulating intracellular calcium, Ocm not only effects cell hyperpolarization but also cell motility via actin polymerization and depolymerization which is largely dependent on [Ca2+]i. The long term goal of the lab’s studies is to understand progressive hearing loss and develop a platform upon which investigation of therapeutics could be possible.
| Mr. Jaideep Dudani
Mr. Jaideep Dudani
Mentor: Dr. Dino Di Carlo
Title: High-throughout Cellular Sample Preparation Through Rapid Inertial Solution Exchange (RInSE)
Jaideep Dudani is currently a third year Bioengineering major, Biomedical Research minor working in Microfluidic Biotechnology lab directed by Professor Di Carlo since March 2010. He has been working on developing a microfluidic system to replicate numerous macroscale lab procedures in a microscale device for increased automation in sample preparation of cell-based assays.
A high-throughput, miniaturized device that can replicate manual procedures has numerous clinical and research applications. For example, single-cell analysis has been recently recognized, but there is a lack of adequate measurement tools in a clinical setting. Additionally, tools such as flow cytometers have limited ability for detecting low-affinity interactions and often require numerous preparatory steps. This tool would allow to automate the steps required upstream of analytical schemes, thereby making cell based diagnostics possible in clinical environments and the study of previously inaccessible kinetic interactions.
In this technology, cells and large particles are transferred from the sample solution to an exchange solution and ordered into a single stream due to inertial force phenomenon (the expertise of the Di Carlo laboratory). This can be used upstream of laser interrogation for fluorescent assays and immunophenotyping. Additionally, the ability to rapidly transfer the cells to another solution can be used for kinetic studies of interactions that occur at small timescales. Jaideep and other group members will more heavily explore these applications.
Jaideep intends on pursuing graduate school in the field of Bioengineering, hoping to develop tools of value beyond the bench top. He would like to thank Daniel Gossett, Henry Tse, Professor Di Carlo, and the rest of the Di Carlo lab. Additionally, he would like to express his gratitude towards the Howard Hughes Medical Institute and the URC - Sciences office.
| Ms. Grace Fang
Ms. Grace Fang
Mentor: Dr. Benjamin Wu
Funding: Van Trees
Title: Hydrogen Peroxide Reaction Kinetics for Teeth Whitening Applications
Grace Fang is a 4th year undergraduate Bioengineering major and has been conducting research in the Wu lab since September 2010. She has been focusing on the effects catalysts in improving bleaching efficacy for clinical applications, combining diffusion and reaction parameters in in vitro modeling.
Teeth whitening has become a widespread cosmetic treatment for tooth discoloration often using hydrogen peroxide as the bleaching agent through the generation of hydroxyl radicals with highly reactive degradation properties. The hydroxyl radicals move past the stains at the enamel and dentin level, penetrate the tooth pulp, and undesirably irritate sensitive tissue and surrounding nerve causing hypersensitivity and amongst other biological problems.
The exact mechanism of stain degradation remains unknown and few in vitro models have been developed due to difficulty in identifying specific in vivo stains and stain sources. Furthermore, few quantitative analyses have been performed to assess reaction rates of stain degradation and morphological changes in tissue and enamel. We seek to derive a quantitative design, combining both the diffusion and reaction parameters, which can be modified with catalysts to control reactivity in different portions of the tooth.
The aim of this project is to optimize oxidation reactions at the surface of the tooth and minimize active radicals near the inner tissue. We hypothesize that increasing temperature, adding light irradiation, and the use of metal catalysts will significantly increase the reaction rate of stain degradation. There is an optimal combination of catalysts to control reactivity at specific depths in the tooth depending on histology.
After graduating from UCLA, Grace plans to pursue graduate school in Biomedical engineering and hopes to move on towards a career in medicine or industry. She would like to thank URC - Sciences, the Van Trees Foundation, Dr. Benjamin Wu, and the Wu lab group for their generous support and encouragement.
| Mr. Michael Fice
Mr. Michael Fice
Mentor: Dr. Kenneth Dorshkind
Title: Differential Requirements for the PU.1 Transcription Factor in B-1 and B-2 B Cell Development
Michael Fice is a fourth year undergraduate student majoring in Microbiology, Immunology, and Molecular Genetics (MIMG) and minoring in Biomedical Research. Michael’s interest in immunology led him to join the lab of Dr. Kenneth Dorshkind in the department of Pathology and Laboratory Medicine during his sophomore year. Under the mentorship of Enca Montecino-Rodriguez, he is currently studying the differential requirements for different B cell populations, specifically B-1 and B-2 progenitors.
The Dorshkind lab is a developmental immunology lab that studies lymphocyte development from embryogenesis through senescence. Within these cells are two distinct B cell populations that have been identified in mice and humans. B-2 cells are part of the adaptive immune system, while B-1 cells are involved in the innate immune response. B-1 progenitors preferentially arise in a fetal/neonatal wave while most B-2 B cells are generated in the bone marrow after birth. Based on these observations, the Dorshkind lab has hypothesized that the regulation of B-1 and B-2 cell development is distinct. The aim of this project is to test this hypothesis by examining the requirement for expression of the PU.1 transcription factor during B-1 and B-2 cell development. They are specifically studying fetal and adult B cell development in three separate knockout mouse strains using flow cytometry. Taking this differential regulation of B-1 and B-2 development into account will be relevant for stimulating B cell production in various therapeutic scenarios.
Michael would like to thank Dr. Dorshkind for his continued support over the past few years as well as his current mentor Enca Montecino-Rodriguez and former mentor Chad Barber for their countless hours of guidance and help. He would also like to thank the Wasserman family for their generosity, which has allowed him to continue his research. Michael plans to continue his studies next year in medical school.
| Ms. Connie Fung
Ms. Connie Fung
Mentor: Dr. Peter Bradley
Title: Identification and Characterization of Toxoplasma Inner Membrane Complex Palmitoyl Acyltransferases (PATs)
Connie is a fourth year Microbiology, Immunology, and Molecular Genetics major. She has been studying the protozoan Toxoplasma gondii in the laboratory of Dr. Peter Bradley since her second year. Toxoplasma is an obligate intracellular parasite in the phylum Apicomplexa that chronically infects one-third of the human population and causes severe neurological disorders in immunocompromised patients. In addition to being an important global pathogen, Toxoplasma also serves as a model organism for studying other apicomplexans, most notably the malaria parasite Plasmodium falciparum.
Connie’s work seeks to understand the unique cell biology of Toxoplasma and its relevance to disease. Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) to facilitate host cell invasion and parasite replication. Despite the importance of the IMC to apicomplexan pathogenesis, much is still unknown about its basic biology and organization. The Bradley lab identified a family of IMC Sub-compartment Proteins (ISPs) in Toxoplasma and showed that it plays a critical role in coordinating parasite replication. In addition, ISP targeting to the IMC depends on protein palmitoylation. Protein palmitoylation by palmitoyl acyltransferases (PATs) is a mechanism widely used by eukaryotic cells to anchor proteins to membranes. Hence, Connie’s current project aims to identify Toxoplasma IMC-resident PATs to determine the mechanism of ISP sorting within the IMC, the results of which will provide new insight into IMC organization and function.
Connie is graduating in June 2012 and plans to attend graduate school to pursue a Ph.D. in Microbiology. Connie would like to thank the Bradley lab for all their support; she feels especially grateful to Dr. Bradley and Josh Beck for their wonderful mentorship and encouragement. She would also like to thank Dr. Philip Whitcome and the Gottlieb Foundation for their generous support of her research and the URC - Sciences for providing her with this opportunity.
| Mr. Raghav Goyal
Mr. Raghav Goyal
Mentor: Dr. Kang Ting
Title: Nell-1 is Required for Formal Craniofacial Intramembranous and Endochondral Skeletal Growth and Development
Raghav Goyal is a fourth year MCDB major and has been a student researcher at the Dental and Craniofacial Research Institute at UCLA under the mentorship of Dr. Kang Ting since Winter 2011.
Raghav has been studying the effects of NELL-1 deficiency on skeletal development in rats and mice. NELL-1’s importance in bone formation was originally discovered in pathologically fused sutures of non-syndromic coronal synostosis (CS) patients. The lab has found that Nell-1 over-expression in transgenic mice results in a CS-like phenotype with calvarial overgrowth, bone overlap and premature suture closure associated with an increase in osteoblast differentiation. Interestingly, Runx2, like Nell-1, is upregulated in patients with non-syndromic CS. Runx2 has been validated as essential to osteoblastic and chondrogenic lineage differentiation, arising from mesenchymal condensation, notably in the craniofacial skeleton. Additionally, Nell-1 is also known to play a significant role in chondrogenic differentiation and endochondral bone formation in several animal models. Currently, Sox9 has been recognized as a critical transcriptional factor controlling the transition of chondrocytes from the proliferative to hypertrophic stages during endochondral bone formation. Previous studies have revealed that Nell-1 reproducibly inhibits Sox9 expression in cartilaginous tissues. The team hopes to demonstrate that Nell-1 is required for normal craniofacial skeletal growth and development.
Raghav is also working on studies involving the use of NELL-1 to treat osteoporotic phenotypes. Furthermore, in conjunction with recently identified adipose-derived Perivascular Stem Cells (PSCs), the Ting lab has found NELL-1 to induce osteogenesis, thus providing a promising new therapeutic for bone-regeneration.
After graduation, Raghav is planning to spend another year conducting research at Dr. Ting’s lab, after which he plans to attend graduate school in pursuit of a PhD. He would like to thank Dr. Ting and all his mentors at the lab, as well as the MacDowell Scholarship for recognizing his efforts
| Ms. Xin Ning Guan
Ms. Xin Ning Guan
Mentor: Dr. Richard B Kaner
Title: Synthesis and Applications of Nanostructured Polyaniline
Xin is currently a senior undergraduate student majoring in Chemistry-Material Science. She joined Professor Richard Kaner’s laboratory in the Department of Chemistry and Biochemistry as an undergraduate researcher, and started to work on the synthesis and applications of conducting nanostructured polymer in Fall 2010.
Her current research focuses on the scalable synthesis of high aspect-ratio conducting polymer nanowires. Such anisotropic structures can be synthesized by controlling the reaction parameters carefully to prevent secondary growth, which often leads to large agglomerates. She has also been studying to develop synthetic routes to Polyaniline via solution-based self-assembly method. By varying the solvents and time duration, structure-property relationship of Polyaniline can be investigated. The morphology and dimension of this Polyaniline can be monitored through the molecule-solvent interactions.
Xin would like to thank Dr. Richard Kaner, Ms. Yue Wang, and the members of Kaner Lab for their guidance and mentorship. She would also like to thank Northrop Grumman/Litton for their generous support and URC - Sciences for giving her this excellent opportunity.
| Mr. Joseph Hadava
Mr. Joseph Hadaya
Mentor: Dr. Aman Mahajan
Title: Role of the Sympathetic Nervous System in Arrhythmogenesis
Cardiovascular disease is the leading cause of mortality in the United States. One of the most lethal conditions is ventricular tachycardia, which often degenerates into ventricular fibrillation, in which case the individual dies unless cardioverted immediately. Treatment options to terminate ventricular tachycardia range from pharmacological interventions, insertion of implantable cardioverter-defibrillators, and radio frequency catheter ablation of the arrhythmogenic substrate. However, in some patients, even after utilization of these therapies, ventricular tachycardia is not terminated.
With advances in the field of neurocardiology, there is increasing evidence for the role of the sympathetic nervous system in sustaining refractory arrhythmias. Recent clinical evidence has shown that, in patients with these arrhythmias, left cardiac sympathetic denervation has resulted in decreased occurrences of ventricular tachycardia. Moreover, in some patients, right cardiac sympathetic denervation also had to be performed concurrently to terminate the ventricular tachycardia. The goal of the current study is to determine the differential effects of right versus left sympathetic activation at an electrophysiological and mechanistic level. We hope to understand
how sympathetic activity can modulate the occurrence of arrhythmias as well as to improve the quality of treatments available.
Joseph is currently a senior majoring in Physiological Science. He has been conducting research under the Department of Anesthesiology and the UCLA Cardiac Arrhythmia Center since 2009. He has a keen interest in cardiovascular physiology, as he has studied the heart from an ion channel level to a whole organ-system level. Other than the project at hand, Joseph has studied ischemia-reperfusion injury as well as calcium channel dynamics in ventricular cardiomyocytes. Ultimately, Joseph plans to pursue a career in academic medicine and hopes to remain involved in research throughout his career.
| Ms. Renee Hsieh
Ms. Renee Hsieh
Mentor: Dr. Yi Tang
Title: Endoprotease-Mediated Intracellular Protein Delivery Using Nanocapsules
Renee Hsieh is a fourth year undergraduate student majoring in chemical and biomolecular engineering. She is fascinated by the concepts and operations of biotechnology, which led her to Dr. Yi Tang’s laboratory that focuses its interests in natural product biosynthesis and biocatalysis. Due to the increasing attention in the application of protein therapeutics, the Tang laboratory has expanded its interest in research at the interface of nanotechnology, biomaterials and drug delivery. Specifically, the research focuses on the efficient delivery of various biological molecules to cells and model animals for applications in cancer therapy, imaging, vaccination, and programming.
Renee’s current project is to demonstrate the intracellular protein delivery mechanism by using a polymer-protein composite known as Degradable Protein Nanocapsules (DPNCs), involving synthesizing single-protein nanocapsules that can be stable in serum, penetrate the cell membrane and release the protein cargo unaltered. The size, surface charge, and degradability of the polymeric shell can be manipulated and targeting ligands can be inserted onto the surface of the nanocapsules. This project is highly innovative because the use of cytosol-specific enzymes to release and activate functional proteins is an entirely new approach in protein delivery options, and the results will lead to the determination of the feasibility of DPNCs as a new modality for cancer treatment.
After her undergraduate career, Renee plans to work in the industry for a couple years using her expertise in chemical engineering to establish a solid background in operations and engineering design. After obtaining sufficient industrial experience, she wishes to pursue a dual M.D./PhD degree, and devote her knowledge to research in oncology. Renee would like to recognize and express her sincere gratitude to Ms. Carter for her generous donation, Professor Yi Tang for his support and resources, and Muxun Zhao of Tang Laboratory for being a superior mentor and colleague.
| Ms. Jee Youn Hwang
Ms. Jee Youn Hwang
Mentor: Dr. Richard Kaner
Title: Fabrication of Flexible, Light Weight Supercapacitors Based on Freestanding Graphene/polyaniline Films
Jee Youn Hwang is currently a fourth year undergraduate student majoring in Chemistry. She has participated research in the lab by professor Kaner. The research that the incorporation of an electrochemically active second phase in a carbon based freestanding electrode can dramatically enhance the electrode capacitance and thus make high performance supercapacitors. Graphene is an intriguing two dimensional carbon material and has attracted much research attention due to several breakthroughs in fundamental research and promising practical applications. It has ! extraordinary electrochemical and mechanical properties comparable to or even better than carbon nanotubes. Conducting polymers, on the other hand, have high specific capacitance but relatively weak mechanical properties. To improve the performances or extend the functions of the devices, conducting polymers usually have to be nanostructured. Thus, combining the properties of graphene papers and polyaniline nanofibers within flexible electrodes would be interesting for high performance flexible supercapacitors required for portable electronics. Current research final goal is measuring the device’s figure of merit such as gravimetric capacitance, energy density and maximum power density and relate that to previously reported values. And the expectation is a device with high flexibility, conductivity and excellent gravimetric capacitance outperforming many other currently available carbon-based freestanding electrodes.
Jee Youn will graduate in spring 2012, and she will spend time to prepare graduate school of Chemistry. First of all, she would like to thanks to Dr. Kaner that she can take opportunity of being in research group, and it really motivated her to be more patient and energetic on her studying, it affects her willing to study more for professional science. Also as a lab member, thanks to Maherk to help and guiding in the general process of lab. She would like to thanks to Gottlieb for scholarship to help fund her research and academic motivation.
| Mr. Jose Jacob
Mr. Jose Jacob
Mentor: Dr. Feng Guo
Title: Determination of Lin-28 Protein Structure and Molecular Mechanisms of how Lin-28 Regulates Maturation of let-7 miRNAs
Jose is a senior at UCLA and is currently working in Dr. Feng Guo’s Lab. He is investigating molecular mechanisms involved in Lin -28 protein and let-7 miRNAs interaction, and is also attempting to obtain structural details of this protein via X-ray crystallography. MicroRNAS (miRNAs) are a class of non-coding RNAs known to post- transcriptionally repress the expression of a large number of protein-coding genes. Lin-28, a RNA binding protein, interacts with precursors of the let-7 family of miRNAs and inhibits their maturation and biological functions. Let-7 miRNAs are conserved in bilaterian animals; they control developmental timing and function as tumor. It has been suggested that disruption of let-7 processing by activation of Lin-28 could promote the oncogenic phenotype. The precise mechanism by which Lin-28 specifically recognizes let-7 miRNAs is not clearly understood. Furthermore, information regarding the structural details of Lin-28 protein is limited. Hence, structure determination of Lin -28 protein using X-ray crystallography will be attempted. Structures of Lin-28 in complex with cognate RNAs will reveal how this protein specifically recognizes the precursors of let-7 miRNAs. Jose has been also conducting binding assays and gel mobility shift assays using radioactive (P32) let-7 hairpins and Lin-28 protein, in order to study unique biochemical properties and other factors that may regulate their interaction.
After completing his bachelor’s degree in molecular cell and developmental biology (MCDB), Jose intends to pursue a doctoral degree in molecular biology. In the near future, Jose ardently wishes to join the ranks of those researchers who are conducting clinical cancer research, investigating molecular mechanisms involved in cancer metabolism and tumorigenesis. Jose would also like to express his sincere gratitude to all the members of Guo Lab for making his undergraduate scientific life at UCLA wonderful, and for providing him with invaluable support and guidance.
| Mr. James Kelvin
Mr. James Kelvin
Mentor: Dr. Jianwei Miao
Title: Three-dimensional Real-time Mmaging of Gliding Motility in Apicomplexan Parasites Using 4D Dark Field Microscopy
James is a 5th year student majoring in Biophysics. He joined the Miao Group early in 2010 and has worked to establish a new imaging method in dark field microscopy. Currently he is applying the method to the study of parasite motility dynamics.
He has conducted the research project in two phases. In the first phase he set out to prove the utility of dark field four-dimensional microscopy by capturing the three-dimensional evolution of particles with an ultrafast camera. Using gold nanoparticles and subsequently applying visual data analysis via algorithmic deconvolution, he and his lab partner, Thomas Darlington, achieved better time and optical resolutions than other methods in dark field microscopy. In this second phase, he has replaced the gold nanoparticles with the parasites Neospora caninum and Toxoplasma gondii. By employing the same imaging method he hopes that the dynamics of the parasite motility along with the invasion mechanism of host cells can be divined. The deconvolution of the visual data will clear the visual noise from the images and allow vector analysis to shed light on Apicomplexan gliding motility. If such a mechanism can be physically explained, then there could be therapeutic applications for the treatment of Toxoplasma and malarial infection, the latter of which is controlled by the cousin Apicomplexan Plasmodium.
| Mr. Jin Ki Kim
Mr. Jin Ki Kim
Mentor: Dr. Judith Berliner
Title: Role of Ox-PAPC Induced Small G-proteins in Regulating Actin Filament Rearrangement in Human Aortic Endothelial Cells
Jin Kim is a third year undergraduate student majoring in Biochemistry major and minoring in Biomedical Research. He aspires to become a research conducting physician to treat people and discover new cures. Jin eagerly joined the Berliner Lab during the spring of his freshman year (2010) and has been trained as an avid young researcher. While working this lab, Jin has become very passionate about research and is grateful to his Primary Investigator, Dr. Judith Berliner, and Post-Doctorate Fellow, Dr. Sangderk Lee, for their guidance.
The Berliner Lab studies atherosclerosis, which results in heart attack and strokes. In atherosclerosis, the endothelium allows monocytes to infiltrate the blood vessel, initiating a proinflammatory response. The Berliner lab uses Ox-PAPC (oxidized 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine) as a representative molecule that mimics the effect of mm-LDL, which accumulates in the vessel wall during atherosclerosis and activates endothelium for monocyte recruitment to the vessel.
Jin has been examining the effects of Ox-PAPC in regulating Vascular Endothelial Growth Factor Receptor Type 2 (VEGFR2) and downstream molecule small G-proteins to control the endothelial cell (EC) monolayer permeability. He will employ siRNA-mediated gene silencing and chemical inhibitors to find role of VEGFR2 and small G-proteins in regulating Ox-PAPC induced inflammatory process in the endothelium.
| Ms. Kendra Knudsen
Ms. Kendra Knudsen
Mentor: Dr. Robert Bilder
Title: Predictors of Creative Achievement
Kendra is a fourth year undergraduate in Psychobiology. Her passion lies in merging the art of science and the science of art. Since April 2010, Kendra has been working in the Tennenbaum Family Center for the Biology of Creativity as Project Coordinator for Dr. Robert Bilder’s “UCLA300 Project”. The project studies behavioral questionnaires, tests of creativity and cognition and DNA of 300 people to examine selected cognitive phenotypes, determine their patterns of association, and relate them to genetic bases and brain mechanisms.
Creativity encompasses a complex set of discrete behavioral traits that involve generating, manipulating and extending ideas to produce something that is new and useful. Creative achievement is the total novel and useful products individuals generate in their lifetimes. By examining associations among creative behavior, Kendra will assess three alternate models of mediator and moderator effects on creative achievement: (a) intelligence and personality are mediated by creative cognition to predict creative achievement; (b) the effect of intelligence contributes to creative cognition, but the effect of personality on creative achievement is independent; and (c): all three factors contribute to creative achievement independently.
Kendra plans to pursue a doctorate in clinical neuropsychology to investigate how creative thinking may yield health benefits for both the mentally ill and healthy individuals. Through randomized and controlled studies, she hopes to discover how and what elements of creativity and creative motivation are therapeutic to particular, measurable outcomes (e.g., depression, self-esteem) and how best to implement those elements into therapies and everyday life.
Kendra would like to thank Dr. Robert Bilder, her brilliant and encouraging mentor, for his continuous support and guidance. She would also like to express her utmost appreciation to the Milton Gottlieb Estate and for their generous endowment, and the URC - Sciences office in establishing and facilitating such beneficial programs to help students pursue their passions.
| Ms. Jennifer Kuo
Ms. Jennifer Kuo
Mentor: Dr. Lily Wu
Funding: Van Trees
Title: Construction of Functional Androgen Receptor Reporting System to Monitor Efficacy of Androgen Blockade Therapy
Jennifer Kuo is a third year Molecular, Cell, and Developmental Biology major and is completing a minor in biomedical research. She joined the Wu lab in the Department of Molecular and Medical Pharmacology at the beginning of her second year. Her research currently focuses on evaluating the efficacy of androgen blockade therapy in prostate cancer with a functional androgen receptor (AR) reporting system as well as characterizing AR receptor regulation.
Because prostate cancer cells rely on the AR signaling axis for proliferation, the first line of prostate cancer treatment comprises of both androgen deprivation (ADT) and androgen receptor blockade therapy (ARBT). These therapies effectively inhibit androgen/AR signaling levels, and thus disease progression. For patients with advanced prostate cancer, however, therapy remains elusive, with recent studies suggesting that androgen suppression through surgical castration or chemical ablation of prostate tissue is incomplete. To further understand the relationship between androgen levels and cancer progression, and to confirm the efficacy of such hormonal therapies, a monitoring system that incorporates both the PSA and the PSME reporter, which are activated during androgen activity and suppression, respectively, would thus allow a distinction to be made between inhibition of androgen-AR signal and a change in tumor mass. Jennifer will construct and characterize the dual AR reporting system, evaluating its use as a ready readout of anti-androgenic drug action on a mechanistic level, both in vitro and in pre-clinical models. Further characterization of AR regulation will reveal better targets for drug development, providing clinical benefits for prostate cancer treatment.
After graduation, Jennifer hopes to pursue a PhD program and continue research in the biomedical sciences. She would like to thank Dr. Lily Wu, graduate mentor Karen Jiang, and the entire Wu lab for their expert guidance and support. She would also like to thank the Van Trees Foundation for their generous funding support for her research.
| Mr. George Lai
Mr. George Lai
Mentor: Dr. Blaire Van Valkenburgh
Title: Frontal Sinus Morphology in Arctoidea Evolution from Terrestrial to Aquatic Species
George Lai is a fourth year Biology major who has been investigating sinus morphology since Winter quarter of ’11. George has a passion for applying knowledge from his undergraduate studies to understand the changes throughout evolutionary history of a relatively unknown part of animals, the paranasal sinuses.
Mammalian paranasal sinuses form when the nasal epithelium escapes the nasal chamber and invades surrounding bones to form the maxilla, sphenoid, ethmoid, and frontal sinus. Among these paranasal sinuses, frontal sinuses exhibit the greatest amount of variation and have been acquired and lost multiple times in mammals. The repeated evolution of these cavities suggests that they play an important role in skull function. The taxonomic super family of arctoid carnivorans—which include bears, raccoon, seals, etc—was quantified for frontal sinus anatomy as this group covers a range from terrestrial to almost exclusively aquatic. With the use of CT technology, three-dimensional models of sinuses were built for data collection and shape variation quantification using Spherical Harmonics; Geometric Morphometrics, on the other hand, was used to quantify shape variation of the skull. These can be analyzed using multivariate statistics, such as PCA, to distinguish the major change, and George’s goal is to find the evolutionary change that induces the loss of the frontal sinus whether it is the shape of the skull for functionality or the degree of aquatic lifestyle.
George plans to pursue his research in medical school after graduation to obtain a MD/PhD degree. George would like to sincerely thank Miller for their generosity and support for undergraduate researchers. He would also like to give special thanks Blaire Van Valkenburgh and Abigail Curtis for their time, support, and guidance and a warm thanks to the Van Valkenburgh lab for a very enjoyable experience.
| Mr. Andy Lee
Mr. Andy Lee
Mentor: Dr. Dino Di Carlo
Title: Deformability Cytometry: Exploration of a Mechanical Biomarker for Clinical Applications
Under the guidance of graduate student Henry Tse, Andy is examining the potential use of a mechanical biomarker to evaluate the metastatic potential of cells by a deformability cytometer developed by Di Carlo Lab.
Early diagnosis is required for effective treatment of a number of diseases. Cancer outcomes are improved with early detection and aggressive treatment, and the development of diagnostic tools for early detection has generated considerable interest. A label-free and real time mechanical cancer biomarker would thus be an ideal development in the field of cancer screening and diagnosis.
As cells progress through the cell cycle, they undergo cytoskeletal changes that affect their deformability. Mechanical biomarkers related to the remodeling of cytoskeletal and nuclear structures can thus be used to identify cell cycle status, as well as other cellular properties. In particular, cancer cells undergo abnormal molecular signaling that alters their cytoskeletal structure. These changes improve their ability to contract or stretch, influencing the mechanics of cellular deformation. The motility of cancer cells has been shown to be significantly greater than that of normal cells, promoting tissue invasion and metastasis.
Andy aims at setting a quantitative standard for diagnosing malignancy of pleural effusion fluid using a mechanical biomarker. Deformability measurements will be performed on cells from clinical pleural effusion fluid. In parallel, deformability measurements will be done on melanoma cells lines and be compared to both known biomarkers of cancer stem cell state and aggressiveness (DNA, CD 271, Actin, Lamin A/C) and the eventual cytopathological diagnosis.
| Ms. Debora Lee
Ms. Debora Lee
Mentor: Dr. Stephanie White
Title: The relationship between dopamine levels and vocal motor deficits in zebra finch after injection of 6-hydroxydopamine (6-OHDA) into area X
Debora Lee is a second year biology major and has been conducting research in Dr. Stephanie White’s Lab since the beginning of her first year. Under the guidance of Dr. Julie Miller, Debora is working on using the zebra finch Parkinson’s model to better understand the relationship between dopamine levels and speech deficits seen in Parkinson’s patients.
Parkinson’s disease (PD) is a movement disorder caused by the loss of dopaminergic neurons in the midbrain. Though PD is typically associated with abnormal limb movement, most patients show speech deficits which may precede non-vocal motor deficits (Harel et al. Brain Cogn, 2004). This raises the prospect of using vocal deficits in zebra finches as early biomarkers for PD. Our laboratory has shown that the neurotoxin 6-hydroxydopamine (6-OHDA) depletes dopamine input to area X, the song-specific region of the basal ganglia in zebra finches, resulting in changes in song that resemble human PD vocal deficits. Debora will further examine how these vocal deficits are linked to the amount of dopamine loss in area X and the midbrain. Results from this project will provide insight into the link between dopamine depletion and vocal behavior in the zebra finch Parkinson’s model as well as a better understanding of the relationship between dopamine levels and speech deficits in PD patients.
Debora would like to thank Dr. White for the opportunity to conduct research as well as Dr. Miller for her mentorship and continued support. She would also like to express her gratitude to the Gottlieb Foundation for their generosity in funding her research.
| Ms. Virginia Li
Ms. Virginia Li
Mentor: Dr. Michael Fanselow
Title: The Stress-Enhanced Fear Learning (SEFL) Model
Ginny Li is a fourth-year undergraduate majoring in Psychobiology and minoring in English. She has long been fascinated by the human brain, and had previously worked with Dr. Gylys in the Nursing department in searching for Alzheimer’s biomarkers throughout the 2010-2011 academic year before beginning work in Dr. Fanselow’s lab on Post-Traumatic Stress Disorder and general fear learning, focusing on the Stress-Enhanced Fear Learning model. Her previous experience in a biomolecular lab has led her to appreciate the physiological changes in the mind, and drew her interest towards changes in corticosterone levels in rats during fear learning and effects on subsequent behavior.
Her current project involves the Stress-Enhanced Fear Learning (SEFL) model, which theorizes that exposure to a traumatic or stressful event will lead to sensitivity in fear conditioning when later exposed to a similar context or stimulus associated with that traumatic event. On a biomolecular level, we find that corticosterone levels in rats are significantly higher in those who have been exposed to the trauma than those who have not, implying that this stress hormone has significant implications in the SEFL model and may lead to the disproportionate fear response in rats who have been exposed to trauma. In studies using drugs to block corticosterone, a significant decrease in the fear response in rats has been observed, providing support for this hypothesis. Ginny hopes to show differences in baseline levels of corticosterone before exposure to trauma as possible indicators of genetic predisposition to sensitivity in fear conditioning. In a developmental study, she will also be comparing responses to multiple reward systems (partial and continuous reinforcement) after subjects have been exposed to trauma in youth to study how early trauma can affect later behavior as an adult.
Ginny would like to express her gratitude to Dr. Michael Fanselow and Jennifer Perusini for providing their guidance and mentorship, and to the rest of the Fanselow lab for creating a stimulating and comfortable working environment. She would also like to thank the Wasserman family for their generous support in her research endeavors.
| Mr. Billy Lin
Mr. Billy Lin
Mentor: Dr. Jau-Nian Chen
Funding: Van Trees
Title: Structure-function Relationship and Physiological Role of Voltage-Dependent Anionic Channel 2 (VDAC2) in the Zebrafish Heart
Billy is a 3rd year undergraduate majoring in physiological sciences. He has been a part of Dr. Jau-Nian Chen’s lab since fall of last year and has been working under the supervision of Dr. Johann Schredelseker.
Billy’s research deals with uncovering structure-function relationships and physiological roles of the outer mitochondrial Voltage-Dependent Anionic Channel 2 (VDAC2) in zebrafish, specifically focusing on the heart. Billy’s and the Chen lab’s work investigates whether the mitochondria plays a role in regulating calcium levels and cardiac contraction via VDAC2, and if so, what structures of VDAC2 are important for such function. Billy is using mRNA injection for overexpression, morpholino injections for knockdown, and zinc-finger nucleases for knock-out generation to study VDAC2 and its physiological function in the heart.
| Mr. Justin Lin
Mr. Justin Lin
Mentor: Dr. Genhong Cheng
Funding: Van Trees
Title: Deciphering Mechanisms of Type I Interferon Regulation of Antibacterial Response Genes
Justin is a third year biochemistry major pursuing a career in pharmacy. He has been working in Dr. Cheng’s lab since spring quarter 2011, and under the guidance of Dr. Cheng as well as graduate student Shankar Iyer, Justin has been researching the role of Type 1 Interferon in the inhibition of antibacterial response.
Viral infections such as influenza cause the human body to generate type I Interferon (IFN). These IFNs function as signaling molecules that alert the immune system of a viral infection and activates genes that are involved in antiviral defense. IFN signaling, however, has recently been shown to inhibit a set of genes that are activated in mounting antibacterial defense, and thus, confer susceptibility to secondary bacterial infections. Activation of type I IFN signaling activates two transcription factors, STAT1/STAT2, which are involved in anti-viral gene expression. The pathway by which they activate these genes has been well studied, and these proteins have been mapped out. However, STAT1/STAT2 also play a role in inhibiting antibacterial response genes. The mechanism by which they inhibit antibacterial responses has not been well studied, and the goal of his research will be to elucidate the mechanism by which they inhibit antibacterial genes.
Justin is grateful to Dr. Cheng, as well as the Cheng lab, for the valuable help and mentorship they have provided. He would also like to thank Ms. Knapp and the Van Trees estate for their support, as well as the Undergraduate Research Center in making this partnership possible.
| Mr. Mark Lin
Mr. Mark Lin
Mentor: Dr. Michael Teitell
Title: The Role of Liver Kinase B1 (LKB1) in B Cell Development and Function
Mark Lin is a fourth-year undergraduate student under the Bioengineering Department. He has been working in Dr. Michael Teitell’s lab under the Pathology Department since February 2009. Research in the Teitell Group focuses mainly on mechanisms of cancer formation and progression, specifically on leukemia and lymphoma that arise during B cell development.
The liver kinase B1 (LKB1) serine/threonine kinase has been identified as a tumor suppressor that is genetically mutated in Peutz-Jeghers Syndrome patients, 93% of whom develop malignancies by the age of 43. The Teitell Group is interested in the role of LKB1 during B cell development, as they have generated a B cell-specific LKB1 knock-out mouse model. Isolated splenic B cells from these mice display an activated cell surface phenotype. His studies are designed to determine whether the loss of LKB1 causes dysregulated B cell activation marker expression versus loss of a suppressive function preventing B cell activation. To do this, he will infect B cell lines with short-hairpin LKB1 knockdown vectors, and assess the expression levels of activation markers MHC-II and CD86 via flow cytometry and qRT-PCR. Furthermore, wild-type and LKB1 knockdown cell lines will be stimulated with activating agents, such as anti-IgM and anti-CD40L antibodies, and then assayed for expression of activation molecules. Similar knockdown studies will be performed in primary splenic B cells to establish a connection between in vitro findings and the in vivo phenotype observed. Results from his studies will help clarify the role for LKB1 in regulating B cell activation and normal B lymphocyte development, which is required for an effective immune response and preventative vaccination strategies.
| Ms. Michelle Lissner
Ms. Michelle Lissner
Mentor: Dr. Stephen Smale
Title: The Role of Histone Modifications in Immune System Gene Regulation
Michelle Lissner is a third-year Microbiology, Immunology, and Molecular Genetics major and Biomedical Research minor. She has been conducting research in the laboratory of Dr. Stephen Smale since January 2011. Under the guidance of Dr. Smale and Justin Langerman, she has been examining histone modifications of immune system genes to understand molecular mechanisms of gene regulation.
Upon activation by microbial products, a subset of macrophage-specific genes experiences a rapid upregulation of transcription to produce an inflammatory response. Specific chromatin modifications around enhancers and promoters poise genes for this activation.
DNA methylation plays a regulatory function at enhancers. Previously, the Smale lab has found low methylation of cytosines in cytosine-guanine dinucleotides, called CpG sites, at enhancers in ES cells. This suggests that the enhancers are occupied by transcription factors. These unmethylated CpG windows present at certain inflammatory genes are thought to contribute to long-term competence for proper gene expression.
At promoters in differentiated cells, meanwhile, histone modifications as well as DNA methylation strongly influence gene expression patterns. Many inducible macrophage-specific genes have rapid kinetics of activation, requiring open chromatin structure at promoters. Open chromatin structure is marked by low nucleosome density, histone H3 lysine 4 trimethylation, DNA polymerase II binding, and low DNA methylation. Methylation and acetylation at different histones and lysines also play important regulatory roles.
The array of chromatin methylation and histone modifications suggests that transcriptional logic is determined by these marks. However, the context-specific methods of gene regulation are still not fully understood. By analyzing patterns of these histone marks within kinetic classes of immune system genes, Michelle hopes to understand how conserved chromatin modifications influence gene expression patterns in macrophages.
| Mr. Andrew Liu
Mr. Andrew Liu
Mentor: Dr. Yousang Gwack
Title: Swiprosin-1 as an Adaptor Protein Facilitating STIM1-Orai1 Interaction
Andrew Liu is a fourth year Physiological Science major who has completed the Departmental Honors in June 2011. He joined Dr. Gwack’s lab of the Physiology Department in 2009 and has been investigating the regulators of calcium channels in immune cells under Dr. Gwack’s guidance.
Ca2+ is an important secondary messenger affecting diverse cellular signaling pathways. In immune cells, elevated cytoplasmic Ca2+ binds to calmodulin that activates a signal
transduction pathway, which eventually allows nuclear factor of activated T cells (NFAT) to enter the nucleus. NFAT activation pathway regulates T cells activation, proliferation, and cytokine production. Cytoplasmic [Ca2+] in immune cells arise due to activity of Ca2+ -release-activated Ca2+ (CRAC) channels after engagement of antigens with T cell receptors. The pore subunit of CRAC channels, Orai1, was recently identified by Dr. Gwack’s group and was shown to interact with an integral membrane protein on the endoplasmic reticulum called stromal interaction molecule 1 (STIM1) upon ER Ca2+ store depletion. This interaction between Orai1 and STIM1 triggers sustained Ca2+ entry into T cells that activates various signaling pathways including NFAT. Preliminary data in the laboratory has identified an adaptor protein called Swiprosin-1 as an interaction partner of STIM1.
Andrew later demonstrated that Swiprosin-1 not only interacts with STIM1, but it also binds Orai1. Consequently, Swiprosin-1 may be an adaptor protein responsible for facilitating STIM1 and Orai1 interaction. Andrew’s job involves conducting biochemistry assays for structural and functional analyses of Swiprosin-1 with regards to the CRAC channel components. Furthermore, he works to elucidate the role of Swiprosin-1 through investigating its effects on the Ca2+ and NFAT pathways in T cells. It has been identified that a defect in Orai1 leads to severe combined immunodeficiency (SCID), so the study of CRAC regulator provides medical significance in further understanding SCID. In addition, because Orai1 is predominantly involved in immune cell functions, this study will provide basic understanding that may lead to development of drugs targeting immune-related diseases.
Andrew would like to express his utmost gratitude to the Gwack lab’s support and interests in his academic endeavors, and he is especially grateful for Dr. Yousang Gwack’s patience and mentorship. He would also like to thank the Wasserman Family for their acknowledgement and generous sponsorship of his research.
| Ms. Kimberly Loo
Ms. Kimberly Loo
Mentor: Dr. William Lowry
Title: Elucidating the Developmental Maturity of Pluripotent Stem Cell Neural Progenitor Cells
Kimberly Loo is a third year Molecular, Cell, and Developmental Biology major with a minor in Biomedical Research. She has been conducting research under the guidance of Dr. William Lowry since winter quarter of her second year. Kimberly’s current research project focuses on elucidating the developmental maturity of pluripotent stem cell neural progenitor cells.
Human pluripotent stem cells (hPSCs) have the potential to differentiate into many cell types, yet it is not known how similar the process of PSC in vitro development reflects the in vivo process. The Lowry lab has recently found that both human embryonic stem cells and human induced pluripotent stem cells make cells that are more similar to cells found only very early in fetal development. From this work, our lab identified a set of 105 genes whose expression appears to distinguish mature tissue derived cells from those generated from hPSCs. Among some of the differences observed between hPSC progeny and their respective natural counterparts is one set of genes thought to only be expressed in early embryos, and a second set of genes “maturity or specification” genes that fail to be properly induced during in vitro differentiation.
Kimberly aims to perform transfection experiments on PSC-neural progenitor cells to overexpress a set of the “maturity or specification genes” in attempts to successfully manipulate the gene expression of genes misexpressed between PSC derivatives and their natural counterparts to yield more mature, functional cells that both mimic tissue derived cells and functionally replace cells that are lost in disease or injury.
Kimberly is extremely grateful to Dr. William Lowry, biomedical research minor advisor Dr. Ira Clark, graduate student mentor Michaela Patterson, and the entire Lowry lab for their patience, continued guidance, and unwavering support. She would also like to thank the Wasserman Family, Howard Hughes Medical Institute and the HHURP faculty for this amazing opportunity.
| Ms. Jennifer Luh
Ms. Jennifer Luh
Mentor: Dr. Peter Narins
Title: A Study of Distortion Product Otoacoustic Emissions Across Different Species of Living Anurans
Jennifer Luh is a senior undergraduate student majoring in neuroscience and minoring in biomedical research. She has been involved in neuroscience research since the second year of her undergraduate studies and became a part of Dr. Peter Narins’ lab beginning March of 2011. Her project utilizes distortion product otoacoustic emissions as a diagnostic tool to assess the sensitivity and nonlinear compression of acoustic signals in the inner ear of different species of frogs.
Distortion product otoacoustic emissions (DPOAEs) are sounds that are generated by the ear when two acoustic tones of appropriately chosen frequencies are presented. In humans, they can be used for early screening of outer hair cell damage, for monitoring inner and middle ear function, and may also be used for assessing outer hair cell maturation in premature babies. In addition, DPOAEs are a noninvasive means of investigating the inner ear mechanisms involved in the transduction of mechanical sound to neural activity in mammals and other vertebrates. The primary objective of Jennifer’s project is to obtain DPOAE recordings from several different frog species to examine hearing mechanisms in the frog ear. Recording DPOAEs from different species of frogs will provide evidence that can be compared to existing hypotheses and models of frog hearing, and thus contribute to the understanding of spectral decomposition in the inner ear.
Jennifer would like to thank Dr. Peter Narins and Dr. Sebastiaan Meenderink for their invaluable guidance and assistance, as well as Brandon Nguyen for his partnership in undertaking this project. Jennifer also would like to thank the Wasserman family for their generous support.
| Mr. Hansen Lui
Mr. Hansen Lui
Mentor: Dr. Victor Edgerton
Title: The Role of HIF-1 in non-Hypoxic Cancer Cell Metabolism
Hansen is currently a fourth year Neuroscience major also minoring in Biomedical Research. He has been conducting research in the Banerjee Lab since Summer 2011. Under the guidance of Kevin Jones, a postdoctoral student, Hansen is studying the role of HIF-1 in non-hypoxic cancer cell metabolism.
Hypoxia is an oxygen deficient state that is common in large tumors. Cancer hypoxia is infamous in cancer therapy for its ability to foster greater resistance against chemotherapy. In addition, hypoxic cancer cells are demonstrated to be more invasive and tend to metastasize more sporadically. The Banerjee Lab has found that hypoxia-inducible factor 1 (HIF-1), a transcription factor implicated in the shift in cell metabolism during hypoxic conditions, is also active in maintaining the metabolic state of non-hypoxic cancer cells. Hansen’s project involves delineating the molecular pathways involved in regulating HIF-1 so that new strides can be taken to alleviate more invasive forms of cancer.
Hansen would like to thank Dr. Banerjee, Kevin Jones, and Ira Clark from the minor for their endless support, as well as the whole Banerjee Lab for their hospitality. Hansen will be graduating in 2012 and will take a year off working as a lab technician as he applies for medical school or MD-PhD programs.
| Ms. Janice Ma
Ms. Janice Ma
Mentor: Dr. David Heber
Title: Mechanisms of Ellagitannin Metabolites on IGF-1 induced Human Androgen Independent Prostate Cancer Cells
Janice Ma is a third-year undergraduate student studying Biology and Gerontology. She has been conducting research under the guidance of Dr. David Heber and Dr. Yanjun Zhang in the Resnick Immunutrition Laboratory of the Department of Medicine- Division of Clinical Nutrition.
Upregulated growth and survival signaling via IGF-1/IGF-1R axis has been suggested to play a key role in promoting malignant transformation of prostate cancer cell lines. Through the activation of Akt, IGF-1 also induces the activation of mTOR and the accumulation and translocation of beta-catenin into the nucleus, which plays an important role in mobility and contributes to metastatic potential as well as cancer progression. Meanwhile, the slow, complex progression of prostate cancer from androgen-dependent type to more malignant metastatic hormone insensitive type provides for cancer prevention with nontoxic dietary compounds.
Currently, Janice is studying the mechanism whereby pomegranate ellagitannin metabolites impair AKT and ERK phosphorylation and inhibit IGF-1 mediated prostate cancer cell growth, and is particularly interested in investigating the mechanism through which beta-catenin is phosphorylated by Akt, which has not been well elucidated. She is also involved in conducting in vivo experiments to assess the bioavailability of the compounds in animal models, and their effect on xenograft tumor growth in SCID mice. Implications of these studies may ultimately lead to clinical insights in the chemoprevention and management of metastatic prostate cancer in humans.
Janice would like to thank Dr. Heber, Dr. Zhang, Dr. Vicinanza, and all the members of her lab for their guidance, as well as the Oppenheimer Foundation for their generous support. Lastly, she is especially grateful for the research opportunity that the URC - Sciences URSP Program has made possible.
| Mr. Arek Melkonian
Mr. Arek Melkonian
Mentor: Dr. Omar Yaghi
Title: MOF Catalysis
Arek Melkonian studies physical and inorganic chemistry, in addition to mathematics, materials science, and computation. He has been working with Professor Omar Yaghi since the winter of 2011. Since that time, Professor Yaghi has set up a collaboration with the Bouchard group to use various techniques from physical chemistry to study the physical properties of metal-organic frameworks (“MOFs”). Arek’s main research interest is currently the field of MOF catalysis.
The synthesis of MOFs has proliferated in the field of inorganic chemistry in the last 15 years. MOFs are crystalline compounds that are composed of a metal cluster and organic molecules that connect the clusters together. The Yaghi group has reported extensively on strategies for the design and synthesis of MOFs. The group has empirically learned that organic molecules can change the connectivity of frameworks and degree of interpenetration; in addition, MOFs demonstrate exceptional hydrogen and methane storage capacity (or carbon dioxide selectivity). One topic that has not been reported on extensively in the literature is MOF catalysis. Arek is currently interested in investigating the catalytic capabilities of MOFs; that is, their capabilities as microreactors. One can use nuclear magnetic resonance spectroscopy to initiate in situ studies of the chemical reactions that occur in MOFs in order to improve catalytic efficiency in various industrial applications.
| Ms. Anoush Mohtashamnia
Ms. Anousheh Mohtashamnia
Mentor: Dr. Felix Schweizer
Funding: Van Trees
Title: Role of Ubiquitination in Neurotransmitter Release
Anousheh Mohtashamnia is a fourth year undergraduate majoring in Neuroscience with a minor in Biomedical Research. She’s planning to pursue a dual MD/PhD degree after completing her undergraduate studies at UCLA. She has been working on ubiquitination of synaptic proteins under the guidance of Dr. Felix Schweizer since January 2011.
Ubiquitin proteasome system (UPS) is one of the main pathways for protein degradation in eukaryotic cells. However, protein ubiquitination not only mark proteins for degradation, but also serves as a posttranslational modification, which alters protein interactions and protein function. The Schweizer lab has found that UPS inhibition triggers a rapid increase in spontaneous neurotransmitter release. The frequency of excitatory and inhibitory miniature postsynaptic minis increase several fold within minutes of UPS inhibition while the amplitude remains constant, suggesting a presynaptic effect. Pharmacological evidence indicates that the increase in synaptic transmission results from changes in the levels of ubiquitinated proteins in the presynaptic terminal. Anousheh is specifically interested in ubiquitination of the proteins involved in vesicle exocytosis and has focused on SNAP-25, which is a synaptic membrane bound protein responsible for vesicle exocytosis. SNAP-25 is a component of SNARE complex, proteins that primarily mediate vesicle fusion. It has been shown that the stability of SNAP-25 is regulated by polyubiquitination. Since there is evidence for SNAP-25 ubiquitination, it can be a good target to analyze whether mono-ubiquitination which has a less terminal effect on the proteins, is affecting the neurotransmitter release.
UPS has a special role in human chronic neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Effective analysis and accurate measurement of cellular ubiquitin, both free and conjugated to specific proteins can shed some light on the questions about these neurodegenerative diseases. She would like to thank everyone in the Schweizer lab for their help and support of her academic endeavors.
| Ms. Naseem Moridzadeh
Ms. Naseem Moridzadeh
Mentor: Dr. David Glanzman
Title: Characterization of the Development of Habituation of the Startle Response in Zebrafish
Naseem is a fourth year undergraduate in the department of Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. She is applying to medical schools in June of 2012 with the hopes of eventually merging evidenced based research with clinical practice in order to optimize patient care and treatment. Under the mentorship of Dr. Adam Roberts, Naseem has been researching the mechanisms underlying learning and memory in zebrafish as a member of Dr. David Glanzman’s laboratory.
Zebrafish have been growing as a model organism of interest in the field of developmental biology. Harnessing the ever-expanding repertoire of advantages this organism possesses allows for the investigation of the mechanisms underlying synaptic plasticity. Investigation of habituation of the Mauthner cell, a component of the neuronal circuit critical to the C-start escape response exhibited by zebrafish, facilitated the delineation of the parameters encompassing a short-term and an extended-form of habituation. Using high-speed videography to capture the response of zebrafish to auditory and electrical stimuli, a short-term form of habituation was identified. Through pharmacological manipulations, it was demonstrated that although short-term memory is not disrupted by antagonism of glycine or N-methyl-D-aspartate (NMDA) receptors, long-term memory receptors act through an NMDA receptor-dependent mechanism. Further elucidation of these processes at different stages of zebrafish development will allow for the establishment and more widespread use of zebrafish as a model for learning and memory.
Naseem would like to offer her sincere gratitude to Dr. Roberts and Dr. Glanzman for their support and guidance throughout her projects both inside and outside of the laboratory. She would also like to thank the URC - Sciences office for working so hard to provide undergraduates like herself such unique opportunities and programs to further their accomplishments.
| Mr. Parsa Nafisi
Mr. Parsa Nafisi
Mentor: Dr. Daniel Kamei
Title: Improving the Speed of Phase Separation in Aqueous Two-phase Systems for Enhancement of the Detection of Viruses and Proteins with the Lateral-flow Immunoassay
Parsa Nafisi is a fourth-year bioengineering major and has been conducting research under the guidance of Dr. Daniel T. Kamei in the Department of Bioengineering since March 2010. Currently, his project focuses on improving the time of phase separation in aqueous two-phase systems.
Many important applications exist for the rapid detection of biomolecules, such as viruses and proteins. These include detection of biowarfare agents in warzones, disease biomarkers in resource-poor settings, and protein allergens in food manufacturing sites. These applications require a device that is rapid, portable, and requires minimal power and training. A detection method that fits these criteria is the lateral-flow immunoassay (LFA), which is a small nitrocellulose strip that absorbs a sample through capillary action and detects the presence of a target biomolecule through its specific antibody bound to a colorimetric indicator. However, one drawback is that LFA has a lower sensitivity than its lab-based counterparts, such as ELISA. Therefore, the Kamei lab set out to improve upon LFA by combining it with a pre-concentration step, which uses a novel aqueous two-phase micellar system (ATPMS) in a liquid-liquid extraction step. The ATPMS provides a mild environment for the biomolecules, unlike conventional oil-water systems which can denature biomolecules, making their detection difficult. When the ATPMS is heated, a macroscopic phase separation is induced to form of a micelle-poor phase and a micelle-rich phase. While viruses will naturally partition into the micelle-poor phase due to steric, excluded volume interactions with micelles in the micelle-rich phase, proteins are generally smaller in size and therefore do not partition extremely into the micelle-poor phase. To address this, the Kamei lab developed the novel use of colloidal gold nanoparticles (Au-NPs) conjugated to a specific antibody for the target. When mixed into the ATPMS, these Au-NPs bind to the protein and carry it into the micelle-poor phase. By combining the concentration step with LFA, the Kamei lab was ultimately able to significantly improve its detection limit for both viruses and proteins.
Parsa is currently working on improving the speed of the pre-concentration step, since the ATPMS phase separates on the order of hours, much longer than the LFA which is completed in about 15 minutes. To do so, Parsa will be investigating the use of polymer/salt systems, which are known to phase separate in as little as 10 minutes. However, due to the high salt content of these systems, the Au-NPs used for protein partitioning become prone to aggregation due to a screening of the charges on the Au-Nps. Therefore, Parsa will also be investigating the use of polyethylene glycol (PEG) to sterically stabilize the particles by preventing the short distances between particles necessary for attractive van der Waals interactions that promote aggregation.
| Ms. Courtney Neumann
Ms. Courtney Neumann
Mentor: Dr. Peggy Fong
Title: Use of Benthic Habitat Quality Indicators to Assess Macroalgal Effects on Estuarine Environments
Courtney Neumann is a fourth year student majoring in Marine Biology. After transferring to UCLA last fall, she searched for a lab that would combine her passion for conservation with her interest in marine systems. She found the perfect fit in Dr. Peggy Fong’s lab. As an undergraduate researcher, she helps post-doctoral researcher Lauri Green with her work to assess macroalgal effects on estuarine ecosystems.
This year, Courtney will assist in examining characteristics of multiple estuaries along the California coast. Because of the close proximity of estuaries to human development, they are often subject to numerous anthropogenic stressors. These include nutrient enrichment- known to stimulate blooms of ephemeral macroalgae. Excess macroalgae can negatively affect estuarine ecosystems by increasing hydrogen sulfide concentrations in sediments, depleting sediment oxygen and causing declines in infaunal diversity. Loss of infauna, which support higher trophic levels, can have cascading trophic effects.
The goal of our project is to assess macroalgae effects on estuarine communities through measuring benthic habitat quality indicators such as percent macroalgal cover, algal mat thickness, algal biomass and sediment oxygen penetration depth. Estuaries have variability between them based on geographical location, hydrology, nutrient levels, flushing rate, sediment composition and biological composition. As such, we predict macroalgae will have varying effects based on estuary location. Our studies will better understanding of these effects and potentially aid conservationists in developing and implementing management strategies assessing and regulating algal biomass in order to maintain healthy estuarine ecosysytems.
Courtney would like to thank the Wasserman family for their generous support of her research. Special thanks to Dr. Fong and Lauri Green for their continual enthusiasm and mentorship.
| Ms. Elizabeth Min-Jiun Ng
Ms. Elizabeth Min-Jiun Ng
Mentor: Dr. Benjamin Wu
Title: Remineralizing and Whitening Film for Enamel
Elizabeth Ng is fourth year bioengineering major working in Dr. Benjamin Wu’s lab. She is interested in studying how materials can be used in biological applications.
Her dental related research project seeks to develop an alternate method for teeth whitening. Almost a third of adults in the US are dissatisfied with their current tooth color, which has created a multi-billion dollar tooth whitening industry. This project seeks to develop a temporary paint on tooth whitener as an alternative to veneers or peroxide whitening treatments, which affect the structural integrity of teeth and cause hypersensitivity. The micon-scale film consists of a pharmaceutical coating matrix and multiple fillers. Titanium dioxide, a common food additive, is incorporated as a whitening agent. Hydroxyapatite, the main component of enamel, has also been used as a remineralizing agent. Through bioengineering, materials science, and chemistry principals, she hopes to develop a film that meets many specifications, including biocompatibility, strong adhesion to enamel, color control, and remineralizing ability.
Elizabeth hopes to use her research experience and undergraduate studies to obtain a D.D.S. degree in the near future. She would like to thank Dr. Benjamin Wu for his encouragement as a mentor throughout her undergraduate years. She would also like to express her gratitude to the Ehrisman endowment for their generosity and the URC - Sciences office for their support.
| Mr. Takahiro Ohara
Mr. Takahiro Ohara
Mentor: Dr. Xianjie Yang
Title: The Role of Hedgehog Signaling in Photoreceptor Cell Development in the Postnatal Mouse Retina
Takahiro is a fourth year Molecular, Cell, and Developmental Biology major with a minor in Biomedical Research at UCLA. Since the end of his second year, Takahiro has been conducting research in Dr. Xian-Jie Yang's lab at the Jules Stein Eye Institute in the department of Neurobiology and Ophthalmology. Takahiro's project involves understanding the role of the Hedgehog (Hh) signaling pathway in photoreceptor cell development in the postnatal mouse retina.
The Hh family of secreted ligands has been shown to play important roles during the embryonic stages of mouse retinal development. Previously, Dr. Yang's lab has shown that Hh signals regulate retinal progenitor cell behavior by influencing their cell cycle progression and early neuronal fate specification. The role of Hh signaling in the postnatal mouse retina, however, is not well understood. Several expression studies have suggested possible roles for Hh signaling in late mammalian retinogenesis. Moreover, preliminary data with mice, rats, and zebrafish all hint that Sonic Hedgehog, a member of the Hh family, functions as a mitogen and influence late-born retinal cell fates, particularly that of photoreceptor cells. Understanding the mechanism behind photoreceptor cell development will further help understand diseases such as retinitis pigmentosa and age-related macular degeneration, which cause blindness due to photoreceptor cell death. For this project, Takahiro will be conducting expression, loss of function, and gain of function studies to examine how the Hh pathway may regulate the differentiation, development, and maintenance of late-born photoreceptor cells in the mouse retina.
After completing his undergraduate education, Takahiro is planning to pursue an M.D./Ph.D. degree in hopes of becoming a physician scientist. He would like to thank Dr. Kiyo Sakagami and Kelly Cadenas for training him how to perform various techniques, Dr. Yang for her constant guidance and support, Dr. Ira Clark and the Biomedical Research Minor for allowing him to experience research as an undergraduate, Mr. Lau for his generous donation, and the URC - Sciences.
| Ms. Kristin O'Neill
Ms. Kristin O'Neill
Mentor: Dr. Thomas Gillespie
Title: Predicting Species Richness and Endangerment of Relictual Dry Forests in the Pacific Using Satellite Imagery
Kristin O’Neill is a fourth year undergraduate student double-majoring in Geography/Environmental Studies and International Development Studies at UCLA. Her scientific interest is in conserving critical habitat in regions with a high global conservation priority in order to more efficiently protect the areas with the highest levels of endemism and species richness. She aims to produce research in conservation science that is directly applicable in the conservation planning of dry forests on Pacific islands, which are among the most threatened ecosystems worldwide.
Kristin is currently working on a project that utilizes remote sensing to more effectively predict species richness and endangerment of relictual dry forests in the Pacific. There is little field data collected on tropical dry forests compared to other threatened ecosystems, and this project assesses the use of the more readily available satellite imagery for conservation purposes. Her project combines the field data available with remote sensing data in order to better predict the status of the remaining dry forest fragments and to estimate the variation in species richness and endemism across regions. This research will be used to prioritize areas for conservation and to model and predict the sites that are most suitable for restoration.
Kristin’s plans after graduating in June 2012 include two years of community service and then pursuing a PhD in geography. Kristin would like to thank URC - Sciences and the Gottlieb Fund for making this program possible, as well as her mentor, Dr. Tom Gillespie, for his overwhelming encouragement and support throughout the research process.
| Ms. Kristy Ou
Ms. Kristy Ou
Mentor: Dr. Aldons Lusis
Title: Genetic Regulation of Beta-Hydroxybutyrate
A 4th year undergraduate at UCLA, Kristy Ou majors in Math Applied Science while also minoring in Biomedical Research. Her research interests lie in the genetic and molecular cause of human diseases, motivating her desire to study experimental pathology in graduate school. She joined the lab of Dr. Aldons Lusis in fall 2010, where she has been placed under the guidance of Brian Bennett, a postdoctoral researcher.
The Lusis Lab investigates the genetic interactions of complex traits underlying metabolic and cardiovascular disease. Kristy’s first project focused on identifying gene candidates responsible for the regulation of beta-hydroxybutyrate, a metabolite that causes ketoacidosis and severe metabolic complications under high concentrations. She previously performed a genome-wide association study in a population of inbred mouse strains to determine which SNPs were significantly correlated with beta-hydroxybutyrate levels. By using a genome browser and data from microarrays, Kristy identified Acsf2 and Abcc3 as possible candidates; they both reside within the boundaries of the associations, they are expressed highly in the liver, and their expression levels strongly correlate with beta-hydroxybutyrate levels. Meanwhile, she has been preparing for hepatic knockdown experiments of these candidates by developing an effective siRNA transfection protocol that would allow her to both silence expression of the candidates and measure changes in beta-hydroxybutyrate levels in the cell media. This way, she will be able to determine the role of the candidate genes in ketone body regulation. The results of this experiment will provide insight to the cause of ketoacidosis, which can lead to better therapeutic targets and preventative measures.
Kristy would like to thank Dr. Bennett and Dr. Lusis for providing her an opportunity to conduct research on an independent project. She would also like to express her gratitude towards the URC - Sciences program and the Boyer Foundation for their support in undergraduate involvement in science and research.
| Mr. Darren Pan
Mr. Darren Pan
Mentor: Dr. Guoping Fan
Title: In Vivo Deletion of De Novo Methylation Function On Neural Development in the Murine Cortex
Darren Pan is a third-year UCLA undergraduate majoring in Molecular, Cell, and Developmental Biology who has been conducting research on DNA methylation in Dr. Guoping Fan’s lab since his freshman year under the mentorship of Dr. Juehua Yu. Darren’s interested and focus lies in the mechanisms by which DNA methylation regulates neural development in mammals. His research project aims at identifying the roles specific DNA methylation enzymes play in neurogenesis in mice through loss-of-function analyses.
Neural development in mammals requires proper regulation of gene expression via epigenetic mechanisms. A major epigenetic factor in gene regulation is DNA methylation, a process by which methyl groups added to specific nucleotides selectively inhibit expression of genes by blocking transcription factors or by converting chromatin to a repressive state. The importance of DNA methylation in neural development and function is evident in diseases like Rett syndrome, a mental retardation disorder caused by a mutation in the MeCP2 protein, which binds methylated DNA and represses transcription in healthy individuals.
Although DNA methyltransferases (Dnmts), the enzymes that methylate DNA, have been and are continuing to be studied extensively, they are still not fully understood. Dnmt3a and Dnmt3b have been found to methylate DNA de novo, creating DNA methylation patterns on previously unmethylated DNA, while Dnmt1 uses maintenance methylation which is dependent on initial de novo methyltransferase activity. Knowledge of how each of these enzymes functions independently and during which stages of development will greatly improve our understanding of DNA methylation. Darren is currently analyzing the effects of Dnmt3a and Dnmt3b deletion in the mouse cortex on neurogenesis, comparing the results to previously studied effects of Dnmt1 deletion. He will utilize cryosectioning and immunostaining to assess the effects of deregulation in the cortex caused by the loss of these enzymes, and various motor skill, learning and memory tests will be administered to evaluate possible neurobehavioral defects.
Darren plans on attending medical school upon graduating and ultimately practicing medicine while doing research concurrently. He would like to thank Dr. Fan for giving him the amazing opportunity of joining his lab, Dr. Yu for guiding and continuing to support him, and the Helga K. and Walter Oppenheimer Foundation for generously funding his research.
| Mr. Daniel Perry
Mr. Daniel Perry
Mentor: Dr. Hossein Kavehpour
Funding: Van Trees
Title: Deconvolution of Imaged Collagen Fibers in the Vitreous Humour
Daniel Perry is a senior Electrical Engineering major who has been a member of Dr. Pirouz Kavehpour’s lab since Summer 2010.
Daniel is studying the behavior of collagen fibers in the vitreous humour—the transparent, colorless, gelatinous mass that fills the space between the lens of the eye and the retina lining the back of the eye. Recent research suggests that the grouping of collagen fibers in the vitreous humour may serve as an early warning sign for diseases such as Glaucoma. Daniel will generate the initial images of the vitreous humour using an imaging technique known as phase contrast microscopy, which takes advantage of phase shifts in the light passing through a transparent specimen. Then in an effort to “deblur” the acquired image, Daniel will be applying an image processing technique known as 2-dimensional deconvolution. The technique utilizes known image distortion parameters inherent to the microscope and performs an inverse filtering that produces a resulting image closer to that of the original object. To implement this technique, Daniel will be writing code for the high-level technical computing language and interactive environment, Matlab.
Daniel is currently applying for M.S./Ph.D. programs in Electrical Engineering. He would like to thank his research advisor Dr. Pirouz Kavehpour for his support over the years, the Rex and Ruth Van Trees Estate for their generous contribution to the project, and the URC - Sciences office for their instrumental efforts in introducing undergraduate students to research.
| Mr. Stephen Pham
Mr. Stephen Pham
Mentor: Dr. Margot Quinlan
Title: Elucidating the Role of Cordon-Bleu WH2 Domains in Actin Nucleation
Stephen’s current research lab focuses on understanding the regulation and formation of the actin cytoskeleton within cells. Actin is important for many critical cell functions, thus, many researchers study how and why such actin structures form. In the past, he investigated the mechanisms of Spire, a protein that nucleates actin filaments through Wiskott-Aldrich Syndrome Protein Homology 2 (WH2) domains. His current project aims to elucidate the mechanisms of a nucleator in the same WH2-nucleating class, called Cordon-Bleu (Cobl). Using several biochemical tools, he tests the actin nucleation functionality of different domains within Cobl in vitro to understand each domain’s contribution and to model the overall nucleation mechanism. With such research, in vivo experiments can confirm cellular effects of Cobl as well as other nucleators of its class. Ultimately, this research will help to study the defects and misregulation of actin-related disorders.
Stephen wishes to thank his mentor, Amy Rasson, as well as his P.I., Margot Quinlan, for their constant guidance and mentorship. He is also very grateful for all of the help from the other members of the Quinlan lab.
Stephen intends to participate in a one- or two-year program during which he will teach science or math to underserved youth. Afterwards, he plans to apply to graduate schools and pursue a doctorate degree in Biochemistry, ultimately pursuing a career in teaching and scientific research.
| Mr. Devin Quinlan
Mr. Devin Quinlan
Mentor: Dr. Daniel Kamei
Title: A Modified-transferrin-polyethylenimine Conjugate for the Improved Delivery of Plasmid DNA into Cancer Cells
Devin Quinlan is a fourth year bioengineering major at UCLA. He currently works in the laboratory of Dr. Daniel T. Kamei in the department of bioengineering, where he has been working since the spring of his sophomore year. After graduating from UCLA, Devin plans on pursuing a PhD in bioengineering and then getting a job in the biotech or pharmaceutical industry.
Devin’s research focuses on improving the treatment of prostate cancer. The problem with many cancer therapies today, especially chemotherapy, is that the nonspecificity of the therapeutic drugs leads to toxic side effects, which limits their effectiveness. Thus, one of the goals of the Kamei Lab has been to improve cancer therapy by engineering drug delivery systems that minimize these toxic side effects. Devin’s project focuses improving the delivery of gene therapeutics, which are an attractive tool to treat diseases because they allow for the production of a protein to alter molecular pathways for a custom-tailored effect. Because these therapeutic agents are unable to cross cell membranes, delivery vehicles, such as polyethyleneimine (PEI) have been studied for several years. Additionally, targeting elements, such as transferrin (Tf) have been conjugated to PEI to target them to cancer cells, since its receptor is overexpressed on many types of cancer. This particular strategy, however, may be limited due to the short time Tf spends inside the cell, which reduces the chance of delivering the gene therapeutic. As a solution, the Kamei Lab has previously developed a modified Tf that exhibits a higher cellular association. Devin’s research has focused on using this modified Tf to evaluate a Tf-PEI conjugate that would allow these gene therapeutics to be effectively delivered to treat prostate cancer.
| Ms. Elyse Rankin-Gee
Ms. Elyse Rankin-Gee
Mentor: Dr. Kathrin Plath
Funding: Van Trees
Title: Genome-wide Screening and Characterization of Genes Involved in the Maintenance of the Epigenetically Silenced X Chromosome in Mice
Elyse is a third year Microbiology, Immunology and Molecular Genetics Major. She has been working in the Plath lab since April 2011 with the guidance of Alissa Minkovsky, a MD/PhD student.
In the Plath lab, Elyse studies X chromosome inactivation (XCI) as a model for understanding gene-silencing mechanisms associated with developmental and cell fate changes. XCI is an epigenetic program of transcriptionally silencing of one of two female mammalian X chromosomes to achieve dosage compensation of X-linked genes to male (XY) counterparts. XCI is well studied in mice as a multistep developmental program that occurs very early in embryonic development, during lineage commitment of the pluripotent cells of the inner cell mass. Although many factors such as noncoding RNAs, posttranslational histone modifications, and DNA methylation play a role in XCI, molecular interference with these pathways does not lead to significant X chromosome reactivation. The absence of a key functional factor has motivated the Plath lab to take an unbiased genome-wide approach to look for genes that, when knocked-down by siRNA, lead to X-reactivation. Elyse has aided in the development of the high throughput screen for factors involved in X reactivation and is using a variety of molecular methods to characterize hits. She is hopeful that characterizing an epigenetic process in mammalian cells will shed light on basic mechanisms in cell biology and help the understanding of other epigenetic programs such as those in cancer.
Elyse plans to pursue an MD/PhD after graduating. She would like to thank Kathrin Plath and Alissa Minkovsky for all of their support and guidance. She would also like to express her gratitude to the Van Trees for funding her research. Lastly, she would like to thank URC - Sciences for providing opportunities like URSP that allow undergraduates to pursue their research interests.
| Mr. Erik Reinertsen
Mr. Erik Reinertsen
Mentor: Dr. Benjamin Wu
Title: 3D imaging of Gold Nanoparticle-labeled Cells in Polymer Scaffolds via microCT
Erik Reinertsen, 5th year Bioengineer, Microenvironment Bioengineering Lab, scientific interests include biomaterials, nanotechnology, and mass transport for regenerative medicine and drug delivery, career goal is academic medicine and research, currently applying to MD/PhD programs
Quantitatively analyzing 3D cell distribution in scaffolds is a powerful technique for tissue engineering. The current gold standard for doing so is sectioning and histology. These techniques are time and labor intensive, and result in deformation and destruction of the sample. Spatial resolution is also limited, as slices of sample are analyzed instead of true 3D volume.
These issues have motivated the investigation of microcomputed tomography (microCT) as a noninvasive and high-resolution method of imaging biomaterials. Unfortunately, microCT contrast depends on the attenuation of X-rays through matter, and thus cannot distinguish water-filled cells from the surrounding polymer scaffold.
To address this limitation, Erik will develop gold nanoparticles (AuNPs) capable of being transported inside fibroblasts and pre-osteoblasts, cell lines commonly used in tissue engineering applications. AuNPs have been widely studied for biological applications such as drug delivery, photothermal manipulation, and molecularly targeted imaging. AuNPs feature exceptionally high x-ray attenuation, and are thus attractive as a contrast agent for microCT. Intracellular uptake of AuNPs is a function of particle size and surface chemistry. These parameters will be manipulated to optimize AuNP uptake and thus X-ray contrast. Once AuNP uptake is maximized in simple 2D culture conditions, labeled cells will be seeded onto 3D porous polymer scaffolds and imaged using microCT.
| Mr. Justin Sharim
Mr. Justin Sharim
Mentor: Dr. Peyman Golshani
Title: Cellular Mechanisms of High Frequency Oscillations in the Epileptic Brain
Justin Sharim is currently a senior neuroscience major, as well as founder and editor-in-chief of Autapse, a student neuroscience journal at UCLA. He conducts his research in the Department of Neurology under the guidance of Dr. Peyman Golshani, and has been a member of the Golshani lab since his freshman year. Justin’s current research project focuses on the cellular mechanisms underlying epileptogenesis.
Epilepsy is a devastating neurological disorder characterized by recurrent, unprovoked seizures. After a single prolonged seizure known as status epilepticus, the brain rewires to be predisposed to seizures later in its lifetime. However, little is known about how this rewiring occurs.
This rewiring of the brain manifests itself at the neuronal network level as high frequency oscillations (HFOs) in the hippocampus. Transient bursts of HFOs in the 140-200 Hz frequency band, coined ripples, have been observed in the non-epileptic brain. These oscillations are normal, and have been implicated in various processes such as memory consolidation and synaptic plasticity. In epileptic models however, much faster HFOs of 200-600 Hz, referred to as pathological fast ripples, have been observed. The underlying cause of the pathological HFOs is still unclear. Justin is currently investigating the cellular mechanisms underlying pathological HFOs using electrophysiological techniques. He records simultaneous field potentials and whole-cell membrane potentials from the hippocampus of epileptic and non-epileptic awake, mobile mice running on a spherical treadmill. Using this approach, Justin aims to demonstrate in vivo which classes of neurons fire synchronously in phase with the bursts of the pathological fast ripples. Understanding the cellular mechanisms underlying the genesis of fast ripple oscillations will give insight into how the brain rewires after one extended seizure to predispose it to seizures later in its lifetime. This knowledge may give rise to finding novel treatments targeting the pathways that create the epileptic state.
Justin would like to thank Dr. Golshani for his ongoing support and invaluable guidance. He would also like to thank the Howard Hughes Medical Institute, the Oppenheimer Foundation, and the Undergraduate Research Scholars Program for their generous funding and for fostering his research efforts.
| Ms. Lindsey Sharpe
Ms. Lindsey Sharpe
Mentor: Dr. Andrea Kasko
Title: Galactose-Based Hydrogels for Cell Culture
Lindsey Sharpe is a third year undergraduate studying Bioengineering at UCLA. She has been working in Dr. Andrea Kasko’s lab since Spring Quarter of 2010, focusing in the area of biomimetic glycopolymers.
Most recently, Lindsey has been investigating the synthesis of galactose-based hydrogels for use in cell culture. Galactose has been demonstrated to have a positive effect on hepatocyte growth and adhesion. Promotion of the asialoglycoprotein receptor (ASPGR) interaction can minimize the integrin-mediated pathway in hepatocytes, enhanching phenotypic expression. Ultimately, investigation of hepatocyte behavior on galactose-based hydrogels has potential to contribute to the development of liver tissue engineering, including bioartifical liver-assisting devices and regeneration of liver tissue.
Lindsey is currently applying to Ph.D. programs. She would like to thank the Hilton Foundation and URSP program for their generosity and support of her academic endeavors. She would also like to thank Dr. Andrea Kasko, Mr. Ken Lin, and the rest of the Kasko Laboratory for providing her with the opportunity to have such a fulfilling undergraduate research science experience.
| Mr. Matthew So
Mr. Matthew So
Mentor: Dr. Atsushi Nakano
Title: The Role of Hipk3 in Mammalian Cardiogenesis
Matt is a fourth year studying Microbiology, Immunology, and Molecular Genetics and has been studying cardiac development in the Nakano Lab since March 2011. After joining the Nakano Lab, Matt’s interest in evidence-based research has exponentially increased given the plethora of elusive molecular pathways that have not been thoroughly investigated during cardiogenesis. His current project involves investigating the role of Hipk3 in mammalian cardiogenesis by using mice as his model system.
Mammalian cardiogenesis is tightly regulated by homeodomain transcription factors that ensure the fine tuning of cardiac development. Dysregulation of these homeoproteins causes deleterious diseases including congenital heart disease. It has been shown that homeoproteins interact with co-factors that help direct these homeoproteins to their proper target genes in-vivo through poorly understood signal transduction pathways. One such co-factor, Hipk3, is possibly expressed in cardiomyocytes and reportedly functions as a Serine/Threonine kinase as well as a co-repressor of NK homeoproteins. Hipk3 belongs to the Hipk family and contains a homeoprotein-interacting domain, which allows Hipk3 to interact with NK transcription factors such as Nkx1.2.Though Hipk3 has not received considerable attention, preliminary zebrafish data using Morpholino-knockdown models in the Nakano Lab suggests that its expression may be partly necessary for proper cardiac phenotype development.
Further, it has been shown that all Hipk co-factors contain an evolutionarily conserved kinase domain, and some family members such as Hipk2 have been implicated in Wingless signaling pathways, which promote development of early cardiac precursors in Drosophila. Given the conserved kinase domain, it is conceivable that Hipk3 is also involved in a similar type of signal transduction pathway that Hipk2 promotes, except in the context of murine cardiogenesis.
Matt will employ an in-vivo functional analysis using in-situ hybridization at different developmental stages of the mouse embryo (E8.5-E14.5) to investigate whether Hipk3 is differentially expressed during distinct developmental stages. Further, he will perform immunostaining procedures to assess if Hipk3 co-localizes with transcription factors implicated in cardiogenesis. Lastly, Matt hopes to perform a functional analysis in-vitro by transfecting several kinase-dead mutants into an H9C2 rat line and assessing cellular response. This may elucidate which kinase domain in Hipk3 is responsible for its kinase function.
Matt would like to thank Haruko Nakano, her post-doctorate supervisor, and Austin Nakano, his PI, for graciously allowing him to pursue this research project. Without their guidance, his keen interest for evidence-based research would not be present. With this research, Matt hopes to pursue an MD program, perhaps even in his backyard at UCLA.
| Mr. George Techiryan
Mr. George Techiryan
Mentor: Dr. Michael Gorin
Title: Investigating µ-Opioid Receptor Localization in the Retina
George Techiryan is a fourth year Physiological Science student at UCLA. He has been working in Dr. Michael Gorin’s lab since March of 2010 under the guidance of Dr. Anna Matynia. The lab’s goal is to identify the underlying mechanism by which Photoallodynia (ocular pain from normal levels of light) occurs, using both behavioral and biochemical assays.
Early attempts to produce a reliable model for photoallodynia have resulted in a morphine-induced light aversion (MILA) assay. Morphine is primarily a µ-opioid receptor agonist and could be used to identify pathways involved in this disease. One predicted pathway that engages a subclass of retinal ganglion cells that are intrinsically photosensitive (ipRGC). According to our data, mice lacking the classic photoreceptors still maintain their MILA; however, mice lacking ipRGCs also have MILA. This suggests that any photodetection results in the aversion with morphine. George will be attempting to resolve these data by using both immunohistochemical staining and mRNA expression analysis to identify if the µ-opioid receptor is even located in the retina, and if so, in which cells and at what quantities. This research will provide the first few steps in describing the pathways involved, which would lead to a more direct model of photoallodynia that could be used for testing potential treatments.
George would like to thank Dr. Anna Matynia and Dr. Michael Gorin for the opportunity to learn, work in, and experience what it is like to work in a lab. It has encouraged him to pursue a PhD after medical school and ideally run his own laboratory. He would also like to extend thanks to URSP and Mr. Green for recognition and funding.
| Ms. Chivani Thaker
Ms. Shivani Thaker
Mentor: Dr. Utpal Banerjee
Title: The Effects of Oncogenic Activation on Cell Metabolism Using Drosophila as a Model Organism
Shivani Thaker is a fourth year undergraduate majoring in Molecular, Cell, and Developmental Biology and minoring in Biomedical Research. She has been working in the laboratory of Dr. Utpal Banerjee with her post-doctoral mentor Dr. Kevin Jones since her second year at UCLA. Currently, Shivani is studying the effect of activating various oncogenes on cell cell metabolism using Drosophila as a model organism.
While cells normally break down glucose depending on oxygen availability and undergo oxidative phosphorylation with a high ATP yield in normoxic conditions, cancer cells are unique in that they undergo the typically anaerobic pathway of glucose metabolism, regardless of oxygen presence. This phenomenon, the Warburg effect, or “aerobic glycolysis,” results in lactate production and a low ATP yield. Although the Warburg effect was discovered in the early twentieth century, the mechanisms for the metabolic shift are still not well understood. Thus, Shivani is working with her mentor to dissect pathways downstream of oncogenic activation that ultimately lead to the preferential shift towards aerobic glycolysis. Specifically, Shivani is studying the effects of Notch signaling on cell metabolism in an oncogenic context using the enzyme lactate dehydrogenase as a marker for increased utilization of the anaerobic pathway. Establishing a model for studying cancer cell metabolism in Drosophila will help elucidate mechanisms behind the Warburg effect as well as potential targets that may be exploited for cancer therapy.
After graduation, Shivani plans to pursue a career as a physician-scientist. She is grateful towards the members of the Banerjee Lab, particularly her P.I. Dr. Banerjee and mentor Dr. Kevin Jones for their invaluable guidance and continuous support. She would also like to thank Dr. Ira Clark and Dr. John Olson for sparking and helping develop her interest in research. Finally, Shivani would like to thank Ms. Porteus for her generosity in funding her URSP scholarship.
| Ms. Amy Ton
Ms. Amy Ton
Mentor: Dr. Luisa Iruela-Arispe
Title: Progesterone Selectively Regulates the Expression of Endothelial-Leukocyte Adhesion Molecule VCAM-1 on Endothelial Cells
Amy Ton is a fourth-year student majoring in Molecular, Cell and Developmental Biology and minoring in Biomedical Research at UCLA. Since June 2009, she has been working in the Arispe lab with graduate student Lauren Goddard.
Sex steroids have been highly implicated in the regulation of inflammation. More specifically, progesterone action has been shown to act an anti-inflammatory agent, particularly in regulation of leukocyte trafficking in the female uterus. Our lab is interested in mechanistically understanding how progesterone regulates the inflammatory response by studying the role of progesterone receptor (PR) in leukocyte extravasation. The process of leukocyte extravasation involves the capture of leukocytes from the blood by activated endothelial cells via endothelial-leukocyte adhesion molecules. Our lab has found that PR selectively downregulates the expression of vascular cell adhesion molecule 1 (VCAM-1) as opposed to other adhesion molecules including intracellular adhesion molecule 1 (ICAM-1) and endothelial selectin (E-selectin). To determine the functional implications of our results, Amy will study the binding of leukocytes on progesterone-treated endothelial monolayers. This will be done by using a 2-D flow system, in which different subpopulations of human leukocytes will be flowed over human umbilical vein endothelial cells (HUVECs) overexpressing PR.
In the future, Amy wishes to pursue a dual M.D./Ph.D. degree with the intent to perform biomedical research in an academic setting. Amy would like to thank her mentors Dr. Luisa Iruela-Arispe and Lauren Goddard for their guidance, the Biomedical Research Minor for their ample support, and URC - Sciences for their many opportunities. Amy expresses gratitude to the Wasserman Family for their generous scholarship.
| Mr. Gregory Tong
Mr. Gregory Tong
Mentor: Dr. Ming Guo
Title: Using Genetic Screenings to Identify and Dissect Molecular Mechanisms Leading to Mitochondrial Dysfunction
Gregory Tong is a fourth-year neuroscience student and joined Dr. Ming Guo’s lab in spring 2010. Under the mentorship of Jina Yun, Prajal Patel and Dr. Ming Guo, Gregory has been searching for possible genetic interactions within the Drosophila pink1 molecular pathway.
Parkinson’s disease is the second most common neurodegenerative disease and is distinguished by the loss of dopaminergic neurons in the substantia nigra. In familial forms of Parkinson’s, mutations in PTEN-induced kinase 1 (PINK1), which encodes a serine-threonine kinase localized to mitochondria, and parkin, which encodes a RING finger-containing E3 ubiquitin ligase, (PARK2) have been found. These genes have been shown in Drosophila to interact in a common genetic pathway regulating mitochondrial dynamics, with pink1 upstream of parkin. The net action of this pathway is the promotion of mitochondrial fission and/or inhibition of fusion, and the ability to manipulate the mitochondrial dynamics may prove to be useful in synthesizing novel therapeutic treatments for Parkinson’s. Gregory hopes to utilize genetic screenings to identify possible genetic interactions with the pink1 pathway and further characterize the candidate genes identified.
Gregory would like to thank the Sparks Foundation for their generous support, as well as Dr. Ming Guo, and the Guo Laboratory for their unwavering guidance and support.
| Ms. Vivy Tran
Ms. Vivy Tran
Mentor: Dr. Thomas Otis
Title: Diolistics labeling with DiO/DPA
Vivy Tran is a third year undergraduate studying biology and neuroscience at UCLA. She began working with Dr. Otis in the Department of Neurobiology in spring of her first year, where she began to study GABA receptors and parallel fiber excitability. She then later conducted research on homeostatic plasticity in the cerebellum, examining effects of Purkinje cell firing frequency after TTX admission over time. This project led her to become inspired to truly understand and visualize the intricate connections of the neural network. Vivy currently is studying diolistics in conjunction with DiO/DPA, a labeling technique that will allow a quick and efficient method of visualizing distinct neurons in a network.
Much of the understanding of brain function depends on understanding the structure and organization of the connections made between neurons. These complex interconnections make up vast networks, that when uncovered opens up many possibilities. The possibility to label neurons can help provide a means to show the dynamics of the connections made in these neural networks. Green fluorescent protein (GFP) has been widely used as a way to label neurons in transgenic animals, cell cultures, and brain slices. However as this dye is transfected, there are still difficulties correlated to structural changes in the six hours that GFP expression takes. This in turn can compromise the cells labeled. Diolistics labeling however uses a biolistics delivery of dye to administer DiO (a fluorescent neural tracer dye) to an acute tissue slice. Used in conjunction with dipicrylamine (DPA), a FRET (Förster resonance energy transfer) can be used to report changes in membrane potentials with limited phototoxicity. This technique will provide a means to label neurons without compromising the viability of the cell. Understanding this circuit can thus bring us closer to understanding how cases of epilepsy may look like on this scale.
Vivy is extremely grateful for the support of Dr. Otis and the members within this lab. Their guidance and daily encouragement have been instrumental to her motivation within this field. She would also like to further thank the Gottlieb Foundation for their generosity and support.
| Ms. Shawna Truong
Ms. Shawna Truong
Mentor: Dr. Ren Sun
Title: Exploring and Validating the anti-Interferon Functional Domains in the Hepatitis C Virus Genome
Shawna S. Truong is a fourth-year undergraduate majoring in Molecular, Cell and Developmental Biology. With a keen interest in pharmaceutical drug design and pharmacodynamics, she is conducting research as a member of Dr. Ren Sun’s lab in the Department of Molecular and Medical Pharmacology. Under the supervision of her Ph.D student mentor, Hangfei Qi, Shawna is studying the resistance function encoded by the anti-Interferon (IFN) functional domains of the Hepatitis C Virus (HCV) genome.
Hepatitis C has made its mark as a worldwide disease, with its agent, HCV, amassing a prevalence rate of three percent worldwide- an estimated 200 million people- with a global incidence of 3 to 4 million people annually, according to the World Health Organization. The virus is responsible for eventually causing cirrhosis and hepatocarcinogenesis in individuals afflicted with the disease. There is no vaccine for this virus, and the only available clinical drugs are the combination of IFN and ribavirin with limited success rates. The positive effects of IFN treatment on the disease can only be observed in about fifty percent of patients, indicating that HCV can offset the IFN response pathway. Shawna’s research is centered on systematically studying this anti-IFN function encoded by HCV and how HCV replication of viral mutants is affected in the presence and absence of IFN, as compared to wild-type. The identification and understanding of any domain(s) critical for HCV to establish resistance to IFN will offer novel antiviral treatment strategies and will shed light on vaccine development.
Shawna expresses her sincerest respect and gratitude to Dr. Ren Sun, for providing her the valuable opportunity to conduct great research, and to Hangfei Qi for her constant support and guidance in Shawna’s research endeavors. Shawna would like to warmly thank all the members of Sun Lab for creating an intellectually productive yet enjoyable environment to conduct research in. Shawna also extends her gratefulness to the Boyer fund and UCLA’s URC - Sciences department for promoting students in the pursuit of scientific advancement to bring them steps closer towards achieving their dreams. Last but never least, Shawna wants to assert her deepest admiration, indebtedness and love to her family for their unconditional love and encouragement.
| Ms. Claire Tu
Ms. Claire Tu
Mentor: Dr. Jing Liang
Title: Dihydromyricetin as a Novel Anti-alcohol Intoxication Medication in Fetal Alcohol Exposure
Claire Tu is a third year Neuroscience major and has been conducting research under the guidance of Dr. Jing Liang and Dr. Richard Olsen since Fall 2009. Her current research project focuses on investigating the effects of dihydromyricetin (DHM) as a possible therapeutic candidate for fetal alcohol exposure.
Alcohol targets the GABAA receipt to enhance function and induce plasticity. Ethanol has many neuropharmacological actions including intoxicating, sedative, anxiolytic, reinforcing, and addictive properties that result from a disruption in the delicate balance between inhibitory and excitatory neurotransmission. Our lab has shown that DHM can be a therapeutic candidate to EtOH as it counteracts acute EtOH intoxication and withdrawal signs in rats including anxiety, tolerance, and hyper-excitability. In CNS neurons, DHM antagonizes acute alcohol-induced potentiation of GABAARs and EtOH exposure/withdrawal-induced GABAAR plasticity. DHM also blocks EtOH withdrawal-induced increases in GABAAR alpha 4 subunit levels.
As a Junior URSP scholar last year, Claire designed an animal model of fetal alcohol exposure. The animal model showed that the pups exhibited increased anxiety, tolerance to EtOH, and increased hyper-excitability. Claire is currently studying the effects of DHM on the fetal alcohol model. She is trying to investigate whether DHM can be a therapeutic candidate for fetal alcohol exposure by examining the change in GABAAR's subunit composition, a result of fetal alcohol exposure and withdrawal-induced GABAAR plasticity.
Claire would like to thank Dr. Jing Liang and Dr. Richard Olsen for their continued guidance and support. Furthermore, Claire would like to express her gratitude to the MacDowell Foundation and Undergraduate Research Center for their continued generosity and encouragement.
| Mr. Nolan Ung
Mr. Nolan Ung
Mentor: Dr. Aleksey Matveyenko
Title: Elucidating Beta-cell Clock Gene Expression Following Disruption of Circadian Rhythms
Nolan Ung is a third year Biochemistry major and has been a part of Dr. Aleksey Matveyenko’s lab since Winter 2010. The goal of his research project is to understand clock gene expression in the pancreas with disruptions in light cycles and how it correlates to apoptosis. Nolan will study the effects of the circadian rhythm disruption on bmal-1, click, per-1, and per-2 (clock genes) expression in pancreatic beta-cells by exposing wild-type and diabetic rats to alterations in light/dark cycles. These models will represent certain risks in lifestyle factors like circadian misalignment due to shift work or nocturnal lifestyle. The circadian rhythm allows the organism to adapt its internal metabolism to changes in the external environment. It creates daily “circadian oscillations” of expression in many known physiological functions including glucose metabolism. Differences in clock gene expression will be examined to prove the importance of circadian clock in beta-cell function. It is hypothesized that disrupting the circadian rhythm akin to exposing individuals to shift work or lack of sleep will disturb diurnal changes in the beta-cell clock gene expression. This will ultimately lead to disruption of the beta-cell’s ability to function and survive. Fully understanding these mechanisms will play a crucial role in the treatment of Type 2 Diabetes (T2DM).
Nolan would like to thank Dr. Matveyenko and everyone at the Larry L. Hillblom Islet Research Center for their continued support and guidance. He would also like to thank the Wasserman family for their generous funding. After graduation, Nolan wants to attend medical school and continue his research interests.
| Ms. Ahuva Weltman
Ms. Ahuva Weltman
Mentor: Dr. Warren Grundfest
Title: Terahertz Imaging of Rat Skin Burns
Ahuva Weltman, a Bioengineering senior at UCLA, has worked under the tutelage of Dr. Warren Grundfest since 2007. Her initial research contributions involved synthesizing phantom prostate tissue for use in testing flexible ultrasound devices. She also assisted with testing novel haptic feedback technology for prosthetic advancement. Subsequent research involved using laser-generated shockwaves for the treatment of infected wounds. This project aimed to develop a compact, handheld laser-generated shockwave system that fragments bacterial biofilms on wounds while leaving host tissue intact.
This past summer, Ahuva contributed to research that applies Fluorescence Lifetime Imaging Microscopy (FLIM) techniques to medical applications. Differences in the local chemical and structural environments of human tissue lead to variations in the exponential decay rates of auto-fluorescent tissue. Current research aims to exploit variations in the fluorescence lifetimes between cancerous and healthy tissue to aid histologists in screening samples for cancer and as an intraoperative tool for neurosurgeons performing tumor resections.
This year, Ahuva will help graduate students who seek to use a pulsed terahertz imaging system for burn studies. Terahertz imaging is ideal for burn hydration studies due to the high absorptivity of water in the terahertz region. Initial studies will be conducted on rat models. Delineating the boundaries between burned skin and surrounding healthy tissue will help physicians determine the extent of a burn injury and plan treatment accordingly.
Ahuva thoroughly enjoys taking part in scientific research projects with important, relevant medical applications in mind. Many thanks to Dr. Warren Grundfest—a truly kind and caring mentor. She would like to express her appreciation to the Gottlieb endowment for their gen
| Ms. Shannon Wongvibulsin
Ms. Shannon Wongvibulsin
Mentor: Dr. Benjamin Wu
Title: 3D-Printed Sugar Preforms for Scaffold Creation in Aqueous Environments
Shannon Wongvibulsin is a second year undergraduate minoring in biomedical research, majoring in bioengineering, and performing research in Dr. Benjamin Wu's lab. Because of Shannon's interest in biomedical research, she has been a member of Dr. Wu's lab since the summer before her freshman year at UCLA. While projects of the Wu Lab range from the study of cell interactions with appetite bone matrix to dermal wound healing, they all center upon the study of biomimetic environments for the ultimate goal of tissue repair.
Currently, Shannon is developing a 3D printed sugar preform for ultimate scaffold fabrication. The present goal is to make sugar preforms that can withstand an aqueous environment and serve as a positive mold for infusion of a scaffold solution, such as chitosan-alginate. The long-term aim of this project is the creation of chitosan-alginate scaffolds with zonal micro- and macro-architecture for cartilage and bone regeneration. Ultimately, the 3D printed preform will serve as a positive mold to make chitosan-alginate scaffolds with two zones, one that facilitates bone growth and one that facilitates cartilage growth. Additionally, these two zones of the scaffold will be created to have different pore sizes, larger pores for the bone region and smaller pores for the cartilage region; channels to facilitate the influx of endogenous progenitor cells will also be incorporated into the design of the preform.
Shannon would like to thank all her research mentors for enriching her undergraduate education with the opportunity for hands on experience in solving current biomedical challenges. After graduation, she hopes to pursue an MD-PhD dual degree and contribute to the medical field both as a physician and a member of the research community.
| Ms.Yingfei Wu
Ms. Yingfei Wu
Mentor: Dr. Christopher Colwell
Title: Circadian Dysfunction in Z_Q175_KI Mice, a Huntington’s Disease Mouse Model
Yingfei Wu is currently a 4th year Neuroscience undergraduate student at UCLA. She has been conducting research in Dr. Christopher S. Colwell’s laboratory at UCLA since the fall of 2009. Her senior year project is on analyzing circadian dysfunction in the z_Q175_KI Huntington’s Disease model mice.
Humans have a rhythmic sleep/wake cycle that is maintained by our circadian system, in which the suprachiasmatic nucleus (SCN) in the brain acts as a central clock that synchronizes peripheral oscillators throughout the body. Disruptions in the circadian system are common in human diseases, including Huntington’s Disease (HD). HD patients exhibit sleep disturbances such as difficulty sleeping at night and staying awake during the day, which can have a large impact on their quality of life, as well as that of their caregivers. Previous research on HD mouse models in the Colwell laboratory has shown that their circadian rhythms are disrupted (Kudo et al., 2011). For example, BACHD mice exhibit progressive declines in amplitude of circadian rhythms as measured by wheel-running activity. Yingfei’s project will determine if another line of HD model mice, the z_Q175_KI mice, also exhibit circadian disruptions in behavior and clock gene expression. The results will show whether circadian dysfunction is common in all HD mouse models, and guide the selection of HD mouse models for future rescue experiments that will help with rescuing sleep/wake behavior in HD patients.
Yingfei would like to thank Dr. Colwell, Dr. Loh, and Dr. Kudo for their guidance and support during these past few years, as well as URC - Sciences and Dr. Lewis for their generous funding.
| Ms. Diana Yanez
Ms. Diana Yanez
Mentor: Dr. Atsushi Nakano
Title: Deciphering the Role of NKX2.5 in Sinoatrial Node Development
Diana Alexandra Yanez is a fourth year undergraduate student majoring in Molecular, Cell and Developmental Biology (MCDB) and minoring in Biomedical Research.
She is a member of the Nakano Laboratory, which focuses on studying cardiogenesis. Her research interests are investigating the developmental mechanism of the heart’s pacemaker, the sinoatrial node (SAN). SAN cell malfunction results in fatal arrhythmia including heart standstill and sick sinus syndrome. Although the developmental process of the heart chamber has been molecularly investigated, the mechanism of SAN development has not been elucidated. Elucidating the molecular mechanism of SAN development will lead to a better understanding of fatal arrhythmias and future development of biological pacemakers in the realm of cardiac regenerative medicine. Her project involves the examination of the role that NKX2.5, a transcription factor critical for heart development, plays in SAN. Her current research goal is to determine whether or not Nkx2.5 in Atria inhibits SAN development through paracrine factors. She hopes to define the precise cell-autonomous and non-cell-autonomous role of Nkx2.5 in the process of SAN development.
Diana is planning to continue working in the Nakano lab through her senior year and plans on applying to medical school next year. She would like to thank her family and friends, and all the members of the Nakano Lab for their unconditional guidance and support. She would also like to thank the Carter family for their utmost generosity and encouragement of undergraduate research.
| Ms. Jessica Yang
Ms. Jessica Yang
Mentor: Dr. Nabil Tawil
Funding: Silva Trust
Title: Assessment of fibroblast and keratinocyte migration on fibrin and collagen matrices of different compositions in a 3D modified skin equivalent wound model
Jessica Yang is a fourth year undergraduate at UCLA who is majoring is Bioengineering. She has been working in Dr. Bill Tawil’s lab since spring quarter of 2009. She is currently developing a novel 3D in vitro skin equivalent wound model to study keratinocyte and fibroblast migration during the wound healing process.
The project focuses on studying wound healing in an in-vitro 3D skin equivalent wound model. Wound healing is a complex process that consists of four main steps: hemostasis, inflammation, proliferation, and remodeling of the scar tissue. This model would allow for the study of the complex process of re- epithelialization, which closes up the wound during the proliferation stage, in a setting that closely resembles the in vivo environment. The knowledge of the growth factors or specific concentrations of extracellular matrix components that increase the rate of cellular migration into the wound bed will aid in identifying the dominant parameters that can guide the development of more efficient treatments for faster wound healing rates.
Jessica would like to thank Dr. Tawil for his guidance and the opportunity to research in his lab. She would also like to express her gratitude towards the Silva Foundation and their generous support of her research and for the URC - Sciences program for promoting undergraduate research. Jessica is currently applying for graduate programs in bioengineering and hopes to pursue a career in the biotechnology industry.
| Ms. Linda Ye
Ms. Linda Ye
Mentor: Dr. Natik Piri
Title: The transcriptional regulation of the Rbpms gene
Linda Ye is a fourth-year undergraduate student majoring in molecular, cell, and developmental biology at UCLA. Since April 2009, she has been conducting research in the laboratory of Dr. Natik Piri at the Jules Stein Eye Institute studying the biology of retinal ganglion cells.
Retinal ganglion cells (RGCs) receive the final visual output from preceding layers in the retinal wiring scheme, such as amacrine and bipolar cells, and transmit this image-forming information to the brain. However, the death of RGCs and the degeneration of the axons in the optic nerve are the main causes of vision loss in optic neuropathies, including glaucoma. Despite extensive research in RGC morphology, no genes have been characterized in RGCs, which is a major obstacle in understanding the cause of the degeneration of these cells at a molecular level.
Due to the limited knowledge of RGC biology, previous studies from the Piri lab have aimed to look deeper at the differential gene expression of these cells, and a gene called RNA-binding protein with multiple splicing (Rbpms) was found to be specifically expressed in mouse and human RGCs. Linda is examining the transcriptional regulation of Rbpms with the goals of identifying the gene’s basic promoter region and understanding the mechanisms that drive its RGC-specificity.
Linda would like to thank Dr. Piri, Jacky Kwong, and the rest of the Piri lab for their guidance and support. In addition, she would like to thank the Hilton foundation and UCLA’s Undergraduate Research Center for providing her with this great opportunity.
| Ms. Madeline Yung
Ms. Madeline Yung
Mentor: Dr. Jeffrey Miller
Title: Identifying the mechanisms of sporulation in Bacillus anthracis
Madeline Yung is a graduating Neuroscience major conducting research in the lab of Jeffrey H. Miller in the Department of Microbiology, Immunology, and Molecular Genetics. She currently focuses on the mechanisms by which organisms such as Bacillus anthracis form protective, resistant endospores in response to environmental stress. After graduation, Madeline hopes to pursue an M.D./Ph.D and ultimately a career as a physician.
Bacillus anthracis is a gram-positive bacterium responsible for the disease anthrax. In response to environmental signals, this microbe possesses the ability to differentiate into a durable bacterial endospore in a process called sporulation. Bacillus anthracis spores display resistance to extreme chemical and physical stress, allowing the organism to remain dormant for prolonged periods until it reencounters conditions favorable to growth. Despite the impact that bacterial spores have on the food industry, medicine, and bioterrorism, little is known about the environmental signals and pathways that activate the protein SpoA, a master regulator of sporulation that induces the formation of an endospore.
Previous studies by the Miller lab have shown that genetic knockouts of nprR, which encodes a regulator of the gene for the extracellular protease nprA, display an intriguing ring phenotype when cultured on Luria Broth agar plates for several days. While the bacteria located in the outer ring of each colony undergo sporulation, bacteria located in the center of the ring remain actively dividing, vegetative cells. Madeline’s current project focuses on pinpointing the differences between conditions outside and inside the colony in order to elucidate the environmental signals responsible for inducing sporulation in Bacillus anthracis.
Madeline would like to thank Dr. Jeffrey H. Miller, the Miller lab team, and the Howard Hughes Undergraduate Research Program for their support and inspiration.
| Ms. Hua "Hannah" Zhao
Ms. Hua "Hannah" Zhao
Mentor: Dr. Patricia Phelps
Title: Do dab1beta-gal Mutants Display Mechanical Insensitivity and Thermal Hypersensitivity?
Hannah is a fourth year physiological science major and biomedical research minor. She has been working under the mentorship of Dr. Patricia Phelps since her freshman year in 2009, studying the effects of Reelin in pain sensory.
In the absence of Reelin, its receptors, APOER2 and VLDLR, and the intracellular adaptor protein, Disabled-1 (Dab1), errors in neuronal positioning occur and lead to mechanical insensitivity and thermal hypersensitivity. Previously the Phelps lab has shown these hind paw sensory deficits in reeler and dab1 mutants. Hannah works with the dab1beta-gal mice, which has beta-galactosidase inserted into the endogenous Dab1 gene. Thus the wild type mice will have normal Dab1 expression whereas both heterozygous mice and mutant mice express the beta-gal gene that is easily marked with X-gal histochemistry. Only the mutants, however, have incorrectly positioned neurons in the dorsal horn of the spinal cord.
The lab has performed von Frey and Hargreaves testing on the dab1beta-gal mice and discovered that mechanical and thermal sensitivity in the wild type and heterozygous mice do not differ but mutant mice display mechanical insensensitivity and thermal hypersensitivity. Now Hannah is using immunohistochemical experiments to detect Fos, an indicator of neuronal excitation, following mechanical and thermal stimulations. So far, these data support using the dab1beta-gal mice as a model to study the impact of the Reelin-signaling pathway in pain processing. Then she will use dab1beta-gal mice to elucidate which neurons are involved in the pain circuits that lead to errors in mechanical and thermal sensitivity observed in these mutants.
Hannah would like to thank the Mr. Lau for his generous support of her research, Dr. Phelps for her years of mentorship and support, and the members of the Phelps lab for all their help.
| Ms. Kimberly Bui
Ms. Kimberly Bui
Mentor: Dr. Ellen Carpenter
Title: Genetic and Environmental Components in Possible Mouse Model for Autism
Kim is a third year student currently majoring in Molecular, Cellular, and Developmental Biology. She has been participating in the lab of Dr. Ellen Carpenter since spring of her first year, which focuses within the developing central nervous system and studies the interaction between environment and genetics in order to generate the symptoms of autism within a model mouse. Her current research project investigates the combined effect of decrease in reelin signaling in heterozygous reeler mice and early exposure to organophosphates to these mice and the severity of the resulting neuroanatomical alterations. Mutations observed within the 7q genome locus (where the RELN gene is located) have been associated with the genetic factors behind the autistic phenotype. Reduction in the expression of the extra-cellular matrix protein, reelin, has been shown to correlate with a variety of psychiatric disorders. During development, Reelin causes phosphorylation of the downstream cytosolic adaptor protein disabled 1 (Dab1) by binding to receptors Apolipoprotein E Receptor 2 (ApoER2) and Very-low-density-lipoprotein Receptor (VLDLR) This causes a cascade of events, ultimately resulting in cessation of neuronal migration through the inhibition of tau protein and stabilization of the cytoskeleton. The behavior of the reeler mutant mouse is affected when the mouse is exposed to organophosphate pesticides- in particular, Chlorpyrifos (CPy), shown to inhibit serine protease activity, an element crucial to cell migration. If exposed to these pesticides during development, the hormone regulation of reelin might be affected and result in the autistic phenotype. Kim studies the brain sections of female and male mice of 4 months of age, and uses DAPI staining to observe for any possible lamination errors or disturbances in cortical interneuron and cytoarchitectural organization.
Kim is considering pursuing a career in healthcare sometime after graduating, and would like to thank Dr. Carpenter for giving her the opportunity to conduct research in a lab setting, and thanks all the members of the lab for guiding her over the year and a half that she’s been there. She would also like to thank the Gottliebs for the generous scholarship to help fund her research and gives her appreciation to the Undergraduate Research Center for providing a vast amount of resources.
| Ms. Lisa Cao
Ms. Lisa Cao
Mentor: Dr. Jorge Torres
Funding: Van Trees
Title: The role of key proteins involved in the formation of the mitotic spindle during cell division and their potential as targets for cancer therapy.
Lisa Cao is a third-year undergraduate student majoring in Biochemistry. She has a passion for understanding the mechanism of human cell division and their deregulation in cancer. Lisa joined Dr. Jorge Torres’ lab during winter quarter of 2010. The Torres lab investigates the role of key proteins involved in the formation of the mitotic spindle during cell division and their potential as targets for cancer therapy.
A hallmark of most cancers is an abnormal cell division. This problem occurs during mitosis. The protein XPMC2H has been linked to saving cells from mitotic catastrophe, which is a self-destructive program that is activated when cells fail to divide properly. This leads to the belief that this protein plays a role as a tumor suppressor. However, there is very little information about its cellular and role in mitosis. Lisa’s project aims to clarify XPMC2H’s role cell division through molecular biological techniques, such as gene knockdown and protein purification procedures, hopefully leading to a better understanding of cell division and its mis-regulation in cancer.
Lisa hopes to successfully complete an honors thesis with her knowledge and experience from the Torres lab this year. Working there has been a tremendous opportunity and Lisa would like to thank the lab as a whole and especially Dr. Jorge Torres and Ankur Gholkar, for their continuous confidence, support, and helping hands in her academic and research endeavors. Additionally, she would like to thank her previous mentor Dr. Koki Morizono and the Chen lab for their assistance and guidance. Lastly, Lisa greatly appreciates the generosity and encouragement of the Van Trees Fund as well as URSP program in her research project.