Student Profiles Archive - Amgen Scholars 2014
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. Johnathan Zhao
Pictured: Dr. Hanna Mikkola and Johnathan Zhao
Name: Johnathan Zhao
Home University: UCLA
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Hanna Mikkola
Johnathan Zhao is a UCLA senior majoring in Molecular, Cell, and Developmental Biology and minoring in Biomedical Research. Since spring 2012, he has worked under the direction of Dr. Hanna Mikkola, whose lab studies the generation of hematopoietic stem cells (HSC) during embryonic and fetal development.
HSC are capable of producing all mature blood cell types. Human HSC harvested from donor bone marrow are utilized in transplant therapies against blood disease, but such therapies are vastly limited by low cell counts and tissue-type mismatch between donor and recipient. Thus, learning how to generate sufficient supplies of transplantable HSC in culture would boast major implications for hematological medicine. Critically, HSC rely on their long-term self-renewal ability to expand in number without differentiating. However, the network conferring and maintaining self-renewal during development is unknown.
Johnathan's project focuses on the role of transcription factor c-Myc target protein 1 (MYCT1) in HSC self-renewal acquisition. MYCT1 was found to be highly upregulated in self-renewing HSC compared to non-self-renewing hematopoietic progenitors. In culture, knockdown of MYCT1 expression in HSC ablated self-renewal capacity, while its overexpression delayed HSC exhaustion. After confirming the absence of off-target effects, Johnathan aims to elucidate how MYCT1 imparts self-renewal by both assessing its effect on global transcriptional profiles and identifying its direct gene targets in HSC.
Johnathan would like to thank Dr. Mikkola, postdoctoral mentor Dr. Vincenzo Calvanese, the Mikkola lab, and the Amgen Foundation for their generous guidance and support for his research endeavors.
| Ms. An Qi (Angel) Wu
Pictured: Dr. Genhong Cheng, An Qi (Angel) Wu, and Dr. Yao Wang
Name: An Qi (Angel) Wu
Home University: UCLA
Faculty Mentor: Dr. Genhong Cheng
An Qi (Angel) is a fourth year undergraduate at UCLA, majoring in Psychobiology. She has been working in Dr. Genhong Cheng's laboratory in the Microbiology, Immunology, and Molecular Genetics department since June 2013. Under the guidance of Yao Wang, Angel currently works on projects that involve identifying and characterizing interferon stimulated genes (ISGs), which are a group of genes that are related to viral inhibition in mammalian cells.
Viruses are dependent on host cells for their replication and metabolic functions. While there are numerous types of viruses, each with their own unique structure and protein composition, they all share similar life cycles within the host cell. When under viral attack, the body elicits an innate immune response against the virus by producing interferons (IFNs). IFNs are signaling proteins that can induce the expression of antiviral effectors and these ISGs are capable of inhibiting viruses, both directly and indirectly. ISGs have a wide range of mechanisms from targeting critical stages in the viral life cycle or priming cells for following infections. Identifying the antiviral mechanism of ISGs can further shed light on the details of viral replication, the body's antiviral immune response, and provide us potential new targets for antiviral drugs.
| Ms. Molly Uyeda
Pictured: Molly Uyeda and Dr. Kathrin Plath
Name: Molly Uyeda
Home University: UCLA
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Kathrin Plath
Molly has been in Dr. Kathrin Plath's since the summer of 2013. Vincent Pasque, a post-doctoral fellow, also mentors her. One overarching goal of the Plath lab is to understand how developmental cues stimulate chromatin organization during the pathway to pluripotency via induced reprogramming. More specifically, the Plath lab is invested in understanding the epigenetic mechanisms that control cell fate.
Patient-specific induced pluripotent stem cells (iPSCs) can be easily obtained, but reprogramming is inefficient and its stages and mechanisms remain largely not understood. Since Shinya Yamanaka generated iPSCs in 2006, many new methods of generating iPSCs have been discovered. This provides a unique opportunity to ask if there are only one or multiple paths that somatic cells take on their way to achieving pluripotency. In order to address this question, iPSCs will be generated using traditional methods such as overexpressing pluripotency transcription factors and recent methods such as chemical treatments and overexpressing lineage specific transcription factors. Comparing and contrasting these methods will provide a comprehensive approach to elucidate the epigenetic mechanisms that are responsible for activating the pluripotency network.
| Ms. Melissa Truong
Pictured: Dr. Leanne Jones and Melissa Truong
Name: Melissa Truong
Home University: UCLA
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Leanne Jones
Melissa Truong is a rising senior at UCLA studying Molecular, Cell and Developmental Biology with a minor in Biomedical Research. She has been working in the laboratory of Dr. Leanne Jones since June 2012.
The Jones lab uses the fruit fly Drosophila melanogaster as an in vivo model to study the dynamic interactions between adult stem cells and their niches, which are the specialized microenvironment they reside in. Previous studies have shown that these interactions change in order to maintain homeostasis and in response to stress or aging. Melissa studies a Drosophila gene called headcase, whose molecular function is still unknown. Previous work in the lab identified headcase as a factor required to prevent cell death within certain types of cells in the testis niche. In the intestine, headcase is required for the maintenance of intestinal stem and progenitor cells within the posterior midgut of the adult fly. Melissa's project aims to further explore the role of headcase in the context of tissue-specific knockdown and as a function of age.
Melissa would like to thank Dr. Jones for her ongoing mentorship and guidance, Dr. Pedro Resende for his initial work with headcase in the testis, and the rest of the Jones lab for advice and support. She would also like to extend her gratitude to the Amgen Foundation and its support of undergraduate research and science education.
| Mr. Hamilton Trinh
Pictured: Elizabeth Guenther, Hamilton Trinh, Dr. David Eisenberg
Name: Hamilton Trinh
Home University: UCLA
Faculty Mentor: Dr. David Eisenberg
Hamilton Trinh is a third year student at UCLA majoring in biochemistry. Since the spring of 2013, he has been working with graduate student Elizabeth Guenther in the laboratory of Dr. David Eisenberg studying the structure of transactive response binding protein 43 (TDP-43).
TDP-43 is a transcriptional repressor and splicing regulator implicated in amyotrophic lateral sclerosis (ALS), a debilitating disease that is characterized by the death of motor neurons. Similar to other neurodegenerative diseases such as Alzheimer's and Parkinson's Diseases, research on ALS has revealed that accumulation of proteinaceous deposits is found in affected neuronal cells. In many cases, these deposits contain filamentous aggregates that contain C-terminal fragments of TDP-43. Although aggregation of TDP-43 is apparent, the atomic structure of these aggregates, as well as the mechanism behind the formation of these structures and how they affect the nervous system, is not clearly known. It is hypothesized that the C-terminal domain and truncated second RNA recognition motif of TDP-43 forms aggregates with structures similar to the oligomeric and fibrillar model, two atomic structures that amyloid deposits of Alzheimer's patients display. Hamilton's project involves the structural determination of short segments of TDP-43 aggregated into orderly assemblies of fibrils or oligomers and screening the toxicity of these structures in mammalian cell lines.
| Mr. Justin Toh
Pictured: Dr. Peter J. Bradley, Justin Toh, and Dr. Allan L. Chen
Name: Justin Toh
Home University: UCLA
Major: Microbiology, Immunology, & Molecular Genetics
Faculty Mentor: Dr. Peter J. Bradley
Justin Toh is a 4th year Microbiology, Immunology, and Molecular Genetics major with a minor in Biomedical Research at UCLA. He works in Dr. Peter J. Bradley's lab studying Toxoplasma gondii, an important pathogen for AIDS patients and congenitally-infected neonates. Justin's current project focuses on the Inner Membrane Complex (IMC), a compartment within this parasite that is essential for the parasite's replication.
T.gondii belongs to the large phylum Apicomplexa, a group of intracellular, obligate parasites that causes many veterinarian and medical diseases. The two most significant apicomplexan parasites affecting humans are T.gondii and its close relative Plasmodium falciparum, the causative agent of malaria. T.gondii infects about a third of the human population and is transmitted through the ingestion of raw meat or feline feces.
While the IMC is known for its role in replication, the mechanics of this process remains unknown due to the fact that many of these proteins have not yet been identified. Thus, Justin's project focuses on exploiting a protein interaction method known as BioID within T.gondii to identify novel IMC proteins and characterize these IMC proteins' function by CRISPR/CAS9-mediated knockout. Ultimately, Justin hopes to find IMC proteins that can be used as therapeutic drug targets for this important parasite.
Justin would like to express his gratitude to every member of the Bradley lab, the Biomedical Research faculty, and the Amgen Foundation for their generous support of his undergraduate research and science education.
| Ms. Shayna Stein
Pictured: Juw Won Park, Shayna Stein and Dr. Yi Xing
Name: Shayna Stein
Home University: UCLA
Major: Mathematics of Computation
Faculty Mentor: Dr. Yi Xing
Shayna Stein is entering her senior year at UCLA, majoring in Mathematics of Computation at UCLA. She works in Yi Xing's laboratory of RNA Genomics and Bioinformatics in the Microbiology, Immunology, and Molecular Genetics department. Shayna is currently investigating the effects of single nucleotide polymorphisms (SNPs) on alternative splicing and RNA-Seq alignment.
RNA-Seq is a technology used for identifying alternatively spliced mRNA. RNA-Seq alignment, the first step of RNA-Seq analysis, involves aligning sequenced mRNA fragments to a reference genome. However current methods of RNA-Seq alignment rely on the human reference genome, which does not contain information about mutations in an individual. Hence, alignments are likely to contain inaccurate results regarding the location of splice junctions. As alternative splice events are partially regulated by highly conserved splicing motifs, SNPs can create novel splice sites or corrupt existing splice sites. Consequently, the prevailing method of alignment to the human reference genome may not correctly identify splice sites.
Shayna is testing a new methodology for RNA-Seq alignment that utilizes an individual's SNP information. The goal is to determine whether SNP mutations can generate novel or corrupt existing splice sites, and whether using an individual's SNP information improves RNA-Seq alignment results. The long term goal is to elucidate correlations between alternative splicing altering SNP mutations and disease.
| Ms. Dianne Lumaquin
Pictured: Megan Hoban, Dianne Lumaquin, and Dr. Donald B. Kohn
Name: Dianne Lumaquin
Home University: UCLA
Major: Microbiology, Immunology & Molecular Genetics
Faculty Mentor: Dr. Donald B. Kohn
Dianne Lumaquin is a rising third year undergraduate at UCLA with a major in Microbiology, Immunology, and Molecular Genetics (MIMG) and a minor in Biomedical Research. Since August 2013, she has been an undergraduate researcher in the laboratory of Dr. Donald B. Kohn under the Departments of MIMG and Pediatrics. Under the mentorship of graduate student Megan Hoban, she is conducting a comparison of site-specific genome editing technologies to correct the sickle mutation of the beta-globin gene in hematopoietic stem cells.
Sickle cell disease is the result of an amino acid substitution of valine for glutamic acid in the beta-subunit of hemoglobin due to a point mutation in the gene. Zinc finger nucleases (ZFNs), Transcription Activator-Like Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system are genome editing technologies containing a site-specific DNA binding domain and endonuclease component. ZFNs, TALENs, and CRISPR/Cas9 can target and correct the sickle mutation when delivered alongside a corrected donor template.
Previously designed and constructed ZFNs, TALENs, and CRISPR/Cas9 plasmids have demonstrated targeted cleavage and gene modification at the beta-globin gene in cell lines. Dianne's project focuses on in vitro transcription of ZFN, TALEN, and CRISPR/Cas9 plasmids into functional mRNA, and determining which genome editing technology produces the highest gene modification rate as well as lowest toxicity and off-target activity in hematopoietic stem cells.
| Mr. Phillip Levin
Pictured: Phillip Levin, Dr. Michael S. Levine, and Post Doctoral advisor
Name: Phillip Levin
Home University: California State University, San Bernardino
Faculty Mentor: Dr. Michael S. Levine
Phillip Levin is a Biology major at California State University, San Bernardino. He previously worked in Dr. Theodore Garland Jr. laboratory at UCR, where he studied the neurobiology of mice selectively bred for high voluntary wheel running.
As a UCLA Amgen Scholar, he worked in Dr. Michael S. Levine's laboratory under the supervision of a Post Doctoral mentor. His project focused on Parvalbumin-expressing (PV) interneuron dysfunction in Huntington's Disease (HD). HD is a genetic disorder characterized by time-dependent symptoms and pathology. Symptoms include motor and cognitive impairments. HD pathology includes significant neurodegeneration of medium spiny neurons (MSN) in the striatum and, to a lesser extent, loss of cortical pyramidal neurons (CPN) in the cortex. Both types of neurons are modulated by PV expressing interneurons, which release gamma-aminobutyric acid (GABA).
Levine's laboratory employs electrophysiology and optogenetics to study striatal and cortical PV interneurons in HD. The lab has found dysfunction of PV interneurons in the symptomatic R6/2 HD mouse model, an aggressive form of HD. Presently, the lab is investigating this dysfunction in a slow-progression HD mouse model, Q175, at different stages: pre-symptomatic (3 months), symptomatic (8 months), and fully symptomatic (12 months). Given the time-dependent nature of HD, it is important to explore this dysfunction at different stages of the disease. The purpose of Phillip's project was to determine the nature of PV interneuron modulation of MSNs and CPNs at 8 months in Q175 mice, when brain atrophy is reported, thus providing new insights into the progression of HD neuropathology.
Phillip would like to thank the Amgen Foundation, UCLA, and the Levine Lab for this opportunity.
| Ms. Joan Chou
Pictured: Joan Chou and Dr. Ellen Carpenter
Name: Joan Chou
Home University: UCLA
Major: Integrated Biology and Physiology
Faculty Mentor: Dr. Ellen Carpenter
Joan is a rising fourth year UCLA undergraduate student and began working with PhD candidate Elvira Khialeeva in Dr. Ellen Carpenter's lab in the Department of Psychiatry and Biobehavioral Sciences in September of 2012. Her project focuses on the role of reelin in breast cancer metastasis.
Reelin is an extracellular matrix glycoprotein originally observed to play a significant role in cell migration during brain development. However, recent studies have demonstrated that reelin signaling is also present in other tissues such as the mammary glands, and has been shown to inhibit the migration of mammary epithelial cells lining the lumen of mammary ducts. Preliminary data suggests that loss of reelin signaling decreased the number of breast cancer metastases to the lungs. In these studies, 4T1 mouse mammary tumor cells implanted into the mammary fat pads migrated to the lungs in wild-type mice, forming metastatic nodules. In reeler mice, which carry a naturally occurring deletion mutation in the reelin gene, and in mice that lack Disabled-1, an important intracellular adaptor protein downstream of the reelin signal, the number of metastatic nodules decreased. Recent unpublished data found increases in smooth muscle actin and keratin 14 expression in tumors raised in reeler mice, suggesting a reduction in epithelial to mesenchymal transition. Further, preliminary studies found a difference in the expression of cytokine interleukin-10, suggesting a difference in immune cell activity within the tumors. Her goal is to determine whether reelin expression is required in the tumor environment for primary breast tumor development and maturation.
| Ms. Andrea Chaikovsky
Pictured: Andrea Chaikovsky and Dr. Michael Teitell
Name: Andrea Chaikovsky
Home University: UCLA
Major: Molecular, Cell, Developmental Biology
Faculty Mentor: Dr. Michael Teitell
Andrea Chaikovsky is a senior at UCLA, majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Since January 2013, Andrea has been working in the laboratory of Dr. Michael Teitell in the Department of Pathology and Laboratory Medicine. Her current project seeks to understand how changes in cellular metabolism interact with the process of stem cell differentiation.
Human pluripotent stem cells (hPSCs) rely heavily on glycolysis as their main energy source in order to support their rapid proliferation. As hPSCs differentiate, the metabolic machinery within the cell shifts to rely more heavily on oxidative phosphorylation. Recent studies have indicated that this metabolic transition precedes differentiation, suggesting that metabolic reprogramming may drive or enable the differentiation process. However, the mechanisms that regulate this metabolic transition are not well understood, and it remains unclear how this transition interfaces with differentiation. Andrea's project aims to identify the key metabolic genes whose expression determines the glycolytic or oxidative state of the cell, as well as the transcription factors responsible for changing the expression of these genes upon differentiation. Once these transcription factors are identified, additional studies will determine whether these same regulatory mechanisms influence hPSC differentiation.
| Mr. Timothy Chai
Pictured: Timothy Chai and Dr. Peter Clark
Name: Timothy Chai
Home University: UCLA
Major: Microbiology, Immunology & Molecular Genetics
Faculty Mentor: Dr. Owen Witte
Tim is going be a fourth-year Microbiology, Immunology, and Molecular Genetics major at UCLA. He joined Dr. Owen Witte's lab in the fall of 2012 and has since then worked with postdoctoral fellow Dr. Peter Clark. In collaboration with Dr. Utpal Banerjee's and Dr. S. Lawrence Zipursky's labs, he currently studies ribose metabolism using Drosophila melanogaster as a model organism.
Ribose is the second most concentrated monosaccharide in blood plasma with significant versatility in potential metabolites. It is known that during ribose salvage in mammals, ribose is transported into the cytoplasm and then phosphorylated by ribokinase (RBKS) to ribose-5-phosphate. Next, ribose-5-phosphate can be further metabolized by two pathways: de novo nucleotide synthesis pathway and non-oxidative pentose phosphate pathway. First, in the de novo nucleotide synthesis pathway, ribose-5-phosphate is eventually metabolized into DNA or RNA nucleotide. Alternatively, ribose undergoing the non-oxidative pentose phosphate pathway turns into glycolytic intermediates that can be used for energy synthesis. However, little is known about the physiological role and importance of ribose salvage from the blood plasma.
Previously published work from the Witte lab has shown through PET imaging of mice that ribose accumulates in the liver and attenuates in several models with metabolic syndrome, suggesting a link between ribose salvage and metabolic syndrome. Tim's project will use RNAi knockdown and CRISPR-Cas9 mediated knockout of key enzymes in ribose metabolism pathway of Drosophila melanogaster to elucidate the role of ribose metabolism in vivo.
| Ms. Shannon Zikovich
Pictured: Dr. Siavash Kurdistani, Shannon Zikovich, and Dr. Maria Vogelauer
Name: Shannon Zikovich
Home University: Williams College
Major: Chemistry and Economics
Faculty Mentor: Dr. Siavash Kurdistani
Shannon is a senior majoring in Chemistry and Economics at Williams College. At Williams, she works under the mentorship of Dr. Jimmy Blair studying essential histidine kinase-mediated two-component phospho-signaling pathways as potential targets for the development of new antibiotics.
This summer, Shannon is working in the lab of Dr. Siavash Kurdistani in the Biological Chemistry Department at UCLA to examine whether histone 3 (H3) protects against iron-induced oxidative damage to DNA. Typically, chromatin structure and function is modulated to coordinate DNA-based processes; however, recent findings have elucidated a connection between chromatin and cellular metabolism. In acidic conditions, histones are globally deacetylated, liberating acetate anions that are subsequently co-transported with protons out of the cell and buffering against further acidification. These findings suggest that cancer cells with hypoacetylated chromatin may be experiencing an acidic microenvironment and, consequently, export acetate and protons to maintain their intracellular pH.
Additionally, low pH also releases stores of iron inside the cell and favors formation of the DNA-damaging Fe2+. Thus, one potential mechanism by which chromatin may integrate a response to pH with gene expression may involve iron, as nucleosomes protect DNA against oxidative damage by Fe2+. With evidence of histones' dual role as rheostats regulating pH and protectors against iron-induced oxidative damage, Shannon aims to determine whether certain amino acid residues equip H3 with the ability to protect against iron in the cell. To do so, she'll generate a series of yeast strains harboring specific mutations in H3 and test their sensitivity to oxidative damage.
| Mr. Daniel Chu
Pictured: Dr. Stephen lee, Daniel Chu, Dr. Christina Priest and Dr. Peter Tontonoz
Name: Daniel Chu
Home University: University of California, Santa Barbara
Major: Creative Studies Biology
Faculty Mentor: Dr. Peter Tontonoz
Daniel Chu is a rising senior studying Biology at the UCSB College of Creative Studies and minoring in music (piano performance). At UCSB, he works as an undergraduate researcher under the guidance of Dr. Irene Chen at the Department of Chemistry and Biochemistry investigating the microbial environment in diabetic foot ulcers. The goal of this project is to characterize the bacteriophage metagenome and establish a statistically significant relationship with that of the opportunistic pathogens within chronic ulcers. We are aiming to identify bacteriophages as a potential therapeutic agents and propel the concept of bacteriophage therapy.
At UCLA, Daniel works in the Department of Pathology and Laboratory Medicine under the guidance of Dr. Peter Tontonoz studying transcriptional regulation of lipid metabolism. Lipid metabolism is regulated or modified by regulatory enzymes, which are responsible for post-translational modification of proteins within specific metabolic pathways. Defective regulatory proteins, which will consequently cause dysregulation of certain pathways, can contribute to many metabolic diseases such as elevated blood pressures, atherosclerosis, and cardiovascular disease.
Transcriptional factors are proteins that play an essential role in the regulation of metabolism. They alter the level of expression of certain enzymes within specific pathways, ultimately controlling metabolic homeostasis. Nuclear receptors such as PPARα, PPARγ, LXR, SCREBP1c, and CREB are all transcription factors that are associated with lipid metabolism. The goal of this project is to investigate the role and effect of the gene, BRAP, on these transcription factors that play critical roles in the scope of lipid metabolism.
| Mr. Tyler Schmeckpeper
Pictured: Dr. Jacob Schmidt, Tyler Schmeckpeper, Shiv Acharya
Name: Tyler Schmeckpeper
Home University: Oregon State University
Faculty Mentor: Dr. Jacob Schmidt
Tyler Schmeckpeper is a rising senior at Oregon State University, working towards an Honors Baccalaureate degree in Bioengineering. Back home, Tyler has conducted research under Dr. Greg Herman, whose group is developing an artificial pancreas through electrical and chemical engineering collaboration. In addition, Tyler serves as an Ambassador of Undergraduate Research, where he mentors prospective undergraduate researchers and connects them with professors. At UCLA, Tyler works with Dr. Jacob Schmidt in the Department of Bioengineering to develop biosensors based on artificial membranes.
Lipid bilayers play an integral role in the structure and function of all cell membranes. Among a diverse range of bilayer components are ion channel proteins. Mechanics of these ion channels can be extensively studied in artificially generated lipid membranes through electrophysiological techniques, which can detect various analytes flowing through the membrane by incorporating transmembrane toxin α-hemolysin (αHL).
Tyler's project aims to increase the detection capabilities of these bilayers by incorporating aptamers, nucleic acid sequences engineered to bind various molecules with high specificity. Ligand binding induces conformational changes of these aptamers, thus improving detection efficacy. Furthermore, the project will take advantage of parallelization techniques that utilize artificial bilayer arrays to increase yield and reproducibility. Due to the customizability of aptamers, this project can ultimately broaden the spectrum of analytes detected in ion channels, while simultaneously providing a cheaper and easier method for molecular analysis to rival traditional lab and field techniques.
| Ms. Maxine Nelson
Pictured: Maxine Nelson and Dr. Luisa Iruela-Arispe
Name: Maxine Nelson
Home University: California Lutheran University
Major: Bioengineering and Multimedia
Faculty Mentor: Dr. Luisa Iruela-Arispe
Maxine is entering her final semester at California Lutheran University. She majors in bioengineering and multimedia and has a minor in chemistry. There, she has been working in Dr. Chad Barber's lab for two years studying the role of β1 integrin in relation to KLF2 and blood flow. In collaboration with Dr. Craig Reinhart, they developed a programmable pump system in order to simulate blood flow. Also, she is also a departmental assistant for the bioengineering department and an active member of multicultural and interfaith groups on campus.
At UCLA, Maxine works in Dr. Luisa Iruela-Arispe's lab under the mentorship of Dr. Onika Noel studying direct and indirect roles of cell adhesion protein β1 integrin (β1) in the assembly of extracellular matrix (ECM) during development. Cells are in constant interaction with their surrounding ECM. In a loss of function approach, this lab studies the mechanism by which β1 directly participates in ECM assembly. β1 and focal adhesion proteins (FAs) are responsible for connecting cytoskeleton to ECM. Presence of FAs is studied in vitro with β1 knockout cells under different ECM and integrin-blocking conditions and in mouse aortic tissue. Since ECM affects developing tissue, β1's function in ECM assembly may indirectly affect other tissues, such as the lung. Different microscopy techniques are used to detect how vascular β1 deficiencies lead to defects in ECM of the lung. During her stay, Maxine hopes to contribute to a better understanding of how β1 directly and indirectly affects ECM during development.
| Mr. James Haggerty-Skeans
Pictured: Dr. Patty Phelps and James Haggerty-Skeans
Name: James Haggerty-Skeans
Home University: UCLA
Faculty Mentor: Dr. Patty Phelps
James Haggerty-Skeans is a fourth year Neuroscience student studying at UCLA. He is currently working with Dr. Patricia E. Phelps and PhD candidate Rana Khankan to investigate the effects of immunosuppression on olfactory ensheathing cell (OEC) transplantation and serotonergic axon regeneration after a complete spinal cord transection in rats.
OECs, a unique glial cell found in the olfactory system, normally guide olfactory receptor neurons to their targets in the central nervous system. Following a complete spinal cord transection, OEC transplantation near the lesion site has been shown to support serotonergic axonal regeneration in rodents. Animals that receive OEC treatment have shown improved stepping ability, as well as increased serotonergic axon density in the normally inhibitory injury site. However, it has not yet been shown that OECs survive after transplantation. Additionally, we have found the least amount of OEC survival at 2 and 8 weeks post-injury—time points that directly coincide with primary and secondary immune infiltration waves.
James is currently using fluorescent staining in order to visualize OECs, and gain insight on their survival and behavior at the injury site in immunosuppressed rodents. He hopes that immunosuppression will allow for greater OEC survival after transplantation, as well as increased axon regeneration and hindlimb function recovery.
| Mr. Lawrence Furan
Pictured: Lawrence Furan and Dr. Kendall Houk
Name: Lawrence Furan
Home University: Macalester College
Faculty Mentor: Dr. Kendall Houk
Lawrence Furan is a rising junior chemistry major at Macalester College. He is interested in using computational methods to understand chemical reactions. At Macalester, he works in the lab of Dr. Keith Kuwata using quantum mechanics to determine the mechanisms of organic reactions. As an Amgen Scholar at UCLA, Lawrence continues to study computational chemistry with Dr. Kendall Houk in the Department of Chemistry and Biochemistry.
One of Dr. Houk's goals is to understand the connection between mutations and enzyme activity. The group uses molecular dynamics simulation to observe how mutations change the way the cytochrome P450 enzyme "PikC" hydroxylates a C-H bond. The Houk group's efforts focus on making PikC more useful to chemists by identifying how to make it react quickly and selectively with a wide variety of molecules.
The reaction's rate and selectivity can be improved by mutating certain residues in the active site, stabilizing the substrate's position. Lawrence is studying how the wild type and mutated versions of PikC interact with several non-natural substrate molecules. Tracing the relationships between mutations and the enzyme's reactivity could help the lab predict other beneficial mutations and their outcomes.
Lawrence would like to thank the Houk lab and the Amgen Foundation for providing an opportunity to learn and contribute to this research.
| Ms. Kristen Flynn
Pictured: Dr. Anoklase J.-L. Ayitou, Kristen Flynn, and Dr. Miguel Garcia-Garibay
Name: Kristen Flynn
Home University: Monmouth University
Major: Chemistry with a concentration in Biochemistry & Chemistry with a concentration in Chemical Physics
Faculty Mentor: Dr. Miguel Garcia-Garibay
Kristen Flynn is a rising junior majoring in chemistry with a minor in physics at Monmouth University in West Long Branch, NJ, where she is doing undergraduate research under the guidance of Prof. Massimiliano Lamberto.
As a UCLA Amgen scholar, she will be performing her summer research in the laboratory of Prof. Garcia-Garibay in the Chemistry and Biochemistry department. Her research will focus on the kinetics of excited state processes during photochemical reactions in solid-state. The impetus of her project will answer many questions regarding photochemical reactions in solid-state where precedent studies have shown that solvent free reactions have better yields as well as less side product formation compared to solution phase.
Kristen's summer research will be dealing with photochemical Norrish Type II reactions of crystalline compounds of ketone chromophores, which are prone to undergo hydrogen abstractions that will eventually lead to formation of polycyclic molecular building blocks. Although this reaction has been extensively studied, adequate analytical techniques have been shown to be unsuitable for examining the kinetics of the reaction in solid samples.
Our approach to solve this problem is to make use of nanocrystalline suspensions that display solution phase and crystalline phase properties. Kristen will be using laser flash photolysis instrumentation as well as analytical techniques such as Nuclear Magnetic Resonance, UV/VIS, Infra Red spectroscopies and Dynamic Light Scattering techniques to analyze the systems of interest.
Kristen would like to thank the Garcia-Garibay Lab and the Amgen Foundation for continued support and encouragement in her development as a young researcher.
| Ms. Tamar Feldman
Pictured: Tamar Feldman and Dr. Beth Lazazzera
Name: Tamar Feldman
Home University: University of Washington
Major: Molecular, Cellular and Developmental Biology
Faculty Mentor: Dr. Beth Lazazzera
Tamar Feldman is a rising junior and Microbiology major at the University of Washington. Tamar started undergraduate research in the lab of Dr. Jennifer Nemhauser studying auxin-mediated lateral root development in Arabidopsis thaliana.
At UCLA, Tamar is working in Dr. Beth Lazazzera's lab in the department of Microbiology, Immunology, and Molecular Genetics. She is investigating the role of isoleucyl-tRNA synthetase (IleRS) editing function in Bacillus subtilis during sporulation. IleRS belongs to a family of proteins called aminoacyl tRNA synthetases (AaRS). The AaRS family is responsible for pairing and catalyzing the binding of tRNAs to their cognate amino acids. A subgroup of these proteins, including IleRS, also carry an editing function that hydrolyzes mismatched pairs.
The editing function of some AaRS proteins is important for cellular viability under slow growth conditions, but why is not well-understood. Sporulation, one slow growth process, is induced by nutrient starvation and results in formation of endospores resistant to harsh conditions. B. subtilis ileS (T233P) mutants that lack IleRS editing function have reduced sporulation efficiency. A screen for suppressor mutations that would restore wild type sporulation efficiency resulted exclusively in reversion to the wild type ileS gene.
Tamar's project seeks to quantify the frequency of this reversion. She hopes to learn whether reversion is the only way for ileS (T233P) mutants to regain a high sporulation efficiency or if possible suppressor mutations are being masked by reversion. The existence of other suppressor mutations might reveal where in the sporulation pathway IleRS editing is essential.
| Ms. Imaani Easthausen
Picture: Imaani Easthausen and Dr. Julian A. Martinez-Agosto
Name: Imaani Easthausen
Home University: Bard College
Major: Biology and Mathematics
Faculty Mentor: Dr. Julian A. Martinez-Agosto
Imaani Easthausen is a rising junior majoring in biology with a concentration in mathematics. She attends Bard College located in upstate New York where she is an RA and has dabbled in creative writing and literature coursework in addition to her focus on math and the sciences. Imaani particularly enjoys fantasy stories and spoken word and has written a few short novellas and poems herself.
Imaani has been involved in research projects at Columbia University and Sloan-Kettering Institute. At Columbia, Imaani worked under Dr. David Lederer on an epidemiological project that examined the statistical viability of utilizing lungs from older donors for transplantation. At Sloan-Kettering, she worked under Drs. Jason Lewis and Thomas Reiner on the synthesis of a cancer imaging agent.
This summer, Imaani is working in Dr. Julian A. Martinez-Agosoto's lab. She is studying the Hippo signaling pathway, which is responsible for regulating tissue size by promoting apoptosis and prohibiting cell proliferation. Disruption of the Hippo pathway is associated with hypergrowth and tumoringenesis in mammals. The Hippo pathway is composed of a kinase cascade whose mechanism is well-understood; however, many of the downstream components of the Hippo pathway have not yet been elucidated. The Hippo pathway is evolutionarily conserved and a homologous pathway is found in the fruit fly, Drosophila Melanogaster, making Drosophila an ideal model organism for studying cancers associated with disruption of the Hippo pathway. Imaani will be running a drug screen to identify compounds that are effective in reducing or preventing tumoringenesis in flies. Drugs shown to be promising in reducing tumor growth in Drosophila will also be tested in human cell lines. Additionally, this project will seek to identify unknown downstream components of the Hippo pathway.
| Ms. Sara Daley
Pictured: Brice Curtin, Dr. Patrick Harran and Sara Daley
Name: Sara Daley
Home University: Boston College
Major: Chemistry and Communication
Faculty Mentor: Dr. Patrick Harran
Sara is a rising senior at Boston College studying Chemistry and Communication. She has worked with Dr. Jason Collier and his group at the University of Tennessee analyzing the anti-inflammatory effects of novel arylpyrazole compounds on the beta cell of the pancreas. During her junior year at BC, Sara assisted in the lab of Dr. Jianmin Gao, seeking to optimize the bi-cyclization a cysteine-rich peptide.
Under the direction of Brice Curtin, Sara is working at UCLA to improve upon the synthesis of peptide macrocycles, which enhance a peptide's bioavailability. Macrocycles can be developed by attaching a larger template molecule to a small peptide chain. Therefore, a template molecule with key functionality to bind to a peptide's N-terminus and alkylate an aromatic residue on an amino acid's side chain to form a large ring structure is desired. Additionally, an optically pure template is preferred. Single enantiomers are advantageous in chemical synthesis because their stereochemistry and reactivity is known, leading to products of known arrangement. The template is synthesized following a palladium-catalyzed Negishi coupling of an aryl halide with an alkylzinc compound; the resulting alkyne will be transformed into a cyclopropene through a rhodium-catalyzed carbometalation reaction. To ensure an asymmetric synthesis, several different chiral rhodium-based catalysts will be used to form a stereogenic center in the cyclopropene. Oxidation of the cyclopropene followed by a Grignard reaction completes the optimized template.
Sara would like to thank the Harran Lab and the Amgen Foundation for their continued support in her pursuit of research excellence.
| Mr. Rudy Chen
Pictured: Rudy Chen and Dr. Felix Schweizer
Name: Rudy Chen
Home University: Brown University
Majors: Neuroscience and Music
Faculty Mentor: Dr. Felix Schweizer
Rudy Chen is a rising senior double majoring in neuroscience and music at Brown University. At Brown, Rudy performs research in Dr. Julie Kauer's lab, where he studies the long-term potentiation of GABA neurons onto dopamine neurons in the ventral tegmental area. Rudy has also worked under Dr. Ronald Hammer at the University of Arizona College of Medicine, where he investigated the role of ΔFosB in pre-pulse inhibition recovery induced by repeated administration of a D2 receptor agonist.
This summer, Rudy is working with Dr. Felix Schweizer in the Department of Neurobiology. The Schweizer lab focuses on the ubiquitin proteasome system (UPS), which is most well known for its function in protein degradation. In this process, multiple ubiquitin molecules are covalently attached to a protein by an enzyme. The proteasome then removes the ubiquitin molecules, unfolds the protein, and cleaves it into multiple pieces. However, recent studies have shown that the UPS also plays a significant role in synaptic plasticity. To further investigate the synaptic changes caused by the UPS, Rudy will use electrophysiological techniques on rat hippocampal slices to test if inhibiting deubiquitination significantly affects two measures of plasticity, long-term potentiation and miniature postsynaptic potentials. He will also perform biochemical staining for ubiquitinated proteins after blocking deubiquitination. These studies will help clarify long-term synaptic changes in the hippocampus, which have strong implications in certain types of memory formation as well as diseases affecting the hippocampus, including Alzheimer's disease and anterograde amnesia.
| Ms. Angela Avitua
Pictured: Angela Avitua, Dr. Peyman Golshani and Michael Einstein
Name: Angela Avitua
Home University: University of California, Davis
Major: Neurobiology, Physiology & Behavior
Faculty Mentor: Dr. Peyman Golshani
Angela Avitua is a senior at UC Davis and is majoring in Neurobiology, Physiology & Behavior. She has been a part of Dr. Gene Gurkoff's lab at the Center for Neuroscience in the department of Neurological Surgery since June 2012. Her current project characterizes a new rodent model of pediatric sports-related traumatic brain injury. In the past, she has also worked on projects involving theta frequency stimulation and post-traumatic brain injury epilepsy.
At UCLA, Angela is working in Dr. Peyman Golshani's lab in the department of Neurology where they utilize a mouse model of visual attention to study the electrophysiology of the visual cortex. The ability to pay attention is essential to daily life, and impairments in attention can have a significant effect on quality of life. A number of neuropsychiatric disorders are characterized by attention impairments. Existing pharmacological therapies are often ineffective in treating these disorders and can cause unwanted side effects. Her project aims to better understand the underlying neural mechanisms and circuitry of visual attention so that more specific targets can be identified leading to the development of more effective therapies. It has been shown that attention activates neurons in the visual cortex, but the mechanism remains unknown. To investigate, GCaMP6 calcium imaging will be utilized to visualize the firing rate of neurons in the visual cortex while the animal is performing a visual attention task.