Student Profiles Archive - Amgen Scholars 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. Daniel Wong
Pictured: Daniel Wong & Dr. Julian A. Martinez-Agosto
Name: Daniel Wong
Home University: UCLA
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Julian A. Martinez-Agosto
Daniel Wong is a junior at UCLA, majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Since March 2011, he has been working in the Martinez-Agosto laboratory in the department of Human Genetics. His current project investigates the molecular mechanism through which pico, the Drosophila MIG-10/RIAM/lamellipodin (MRL) protein, regulates systemic larval growth.
Control of tissue and organismal size is coordinated by a number of intracellular growth signal transduction pathways that respond to various extracellular cues. While these growth regulatory mechanisms are crucial to the normal growth and development of animals, dysregulation of these pathways can lead to overgrowth diseases such as cancer. Therefore, elucidating the points in growth signaling pathways at which dysregulation occurs is essential for the development of therapeutic strategies to treat and prevent disease processes such as tumorigenesis.
Daniel's project seeks to characterize the role that MRL proteins play in the communication of these growth regulatory pathways. MRL proteins comprise a specific class of molecular adaptors that connects upstream events, for example, the binding of a ligand to a surface receptor, to downstream targets whose activation brings about a cell response, such as the initiation of proliferation. Using Drosophila melanogaster as a model to study and characterize MRL proteins, Daniel aims to illuminate the role of pico in the regulation of systemic larval growth through examining the link that Pico has to two specific growth signaling pathways: the PI3K/Akt/TOR pathway and insulin signaling.
| Ms. Lauren Wierenga
Pictured: Daniel Cantu, Lauren Wierenga, and Dr. Carlos Portera-Cailliau
Name: Lauren Wierenga
Home University: Kalamazoo College
Faculty Mentor: Dr. Carlos Portera-Cailliau
Lauren Wierenga is a biology major and math minor entering her fourth year at Kalamazoo College. She has worked in the lab of Dr. Debra Yourick at Walter Reed Army Institute of Research studying a form of epilepsy caused by neurotoxin exposure as well as in the lab of Dr. Carlos Brody at Princeton University analyzing learning acquisition in rats. At UCLA, she is continuing to pursue her interest in neuroscience by studying circuit dynamics in a model of fragile X syndrome (FXS) under the mentorship of Daniel Cantu in the lab of Dr. Carlos Portera-Cailliau.
FXS is the most common single-gene cause of autism and results in intellectual impairment and behavioral abnormalities, including seizures and hypersensitivity to sensory stimuli. Recent studies have demonstrated defects in GABA receptors and signaling in the FXS model, causing dysfunction of inhibitory interneurons. Defective inhibitory signaling could potentially lead to the inability of neural circuits to desensitize to a stimulus and result in hypersensitive behavior. Lauren will be investigating the changes in circuit dynamics of the FXS model and testing whether neural circuits in the FXS model fail to desensitize to the chronic presentation of a visual stimulus. This will be accomplished using in vivo two-photon calcium imaging in layer 2/3 of the visual cortex.
| Ms. Tam Tran
Pictured: Dr. Thomas Vondriska and Tam Tran
Name: Tam Tran
Home University: UCLA
Faculty Mentor: Dr. Thomas Vondriska
Tam Tran is a rising junior majoring in Neuroscience at UCLA. She has been conducting research in the laboratory of Dr. Thomas Vondriska since September 2011. Her project involves exploring the relationship between cardiac hypertrophy and fetal gene re-expression, both of which are major components of heart disease.
It has been established that heart disease leads both to cardiac hypertrophy or cell enlargement, and to fetal gene re-expression, but what role hypertrophy itself has in inducing changes in gene expression is unknown. To investigate this, neonatal rat ventricular myocytes will be treated with hypertrophic agonists, after which overall changes in chromatin structure will be examined. This examination will be accomplished both through looking for certain histone post-translational modifications, each of which can be associated either with gene expression or repression, and through DNA digestions, which can show nucleosomal positioning and thus genes' accessibility to transcriptional machinery. By seeing if hypertrophic agonists alone can induce global changes in chromatin structure, the manner in which heart disease-induced hypertrophy is related to fetal gene re-expression can be better understood, which itself will be essential to comprehending how the heart adapts to or fights against disease.
| Mr. Stephen Tran
Pictured: Stephen Tran and Dr. James C. Liao
Name: Stephen Tran
Home University: UCLA
Major: Computational and Systems Biology
Faculty Mentor: Dr. James C. Liao
Stephen is a third year Computational and Systems Biology major at UCLA. He works under Dr. James C. Liao in the Chemical and Biomolecular Engineering Department. The general topic of Stephen's work is developing renewable energy technology. Stephen engineers model bacteria E. coli to produce alcohols such as 1-propanol, 1-butanol, and 1-pentanol, all of which comprise gasoline fuel.
Microbially producing short-length alcohols such as 1-propanol and 1-butanol has been a success so far. As a next step, Stephen is trying to produce even larger alcohols such as 1-hexanol and 1-octanol; these alcohols are preferable to small alcohols because they have higher energy density and are more easily handled by modern industrial machinery.
To achieve biological production of larger alcohols, Stephen is mutating some enzymes involved in E. coli's artificially engineered alcohol production pathway, Keto-isovalerate dehydrogenase and Leucine ABCD. These mutations will enlarge the active sites of these enzymes to enable them to bind to larger precursors which generate long-chained alcohols.
| Ms. Sara Taylor
Name: Sara Taylor
Home University: UCLA
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. Amander Clark
Sara is a fourth year undergraduate majoring in Molecular, Cell and Developmental Biology with a minor in Biomedical Research at UCLA. She works in Dr. Amander Clark's laboratory in the Department of Molecular, Cell and Developmental Biology. Under the guidance of Serena Lee, Sara is investigating a possible role for DNA methyltransferase 1 (DNMT1) in primordial germ cell (PGC) development.
DNA methylation plays an important role in all tissues, where it acts to maintain imprinted genes, silence transposons, and guard against DNA damage. During cell division DNA methylation is reduced by half, therefore a mechanism is required to restore methylation to the newly synthesized daughter strand. This is achieved by DNMT1. Disruption of DNMT1 by targeting the first exon of the N-terminal domain in mice results in early embryonic lethality before embryonic (e) day 11.0 with a substantial loss of methylation. Due to this early embryonic lethality, the effect of a null mutation on PGC development has not been evaluated in detail.
In order to study the effects of the DNMT1 null mutations in the germ line in vivo, the Cre-loxP system will be used to create a conditional knockout of Dnmt1 in PGCs. Based on preliminary in vitro data, there should be fewer PGCs in embryos lacking DNMT1 in the germ line compared to wild type embryos.
| Ms. Laura Taylor
Pictured: Dr. Jeff Abramson, Laura Taylor, and Dr. Aviv Paz
Name: Laura Taylor
Home Institution: Carthage College
Majors: Biology and Neuroscience
Faculty Mentor: Dr. Jeff Abramson
Laura Taylor is a rising senior at Carthage College who is double majoring in biology and neuroscience. At Carthage she works under Dr. Pellino of the chemistry department where she studies a small non-coding RNA in E.coli and its role in cell survival and its repression of the gal operon.
At UCLA Laura is performing research in the Abramson lab where they study the structure of vSGLT, a bacterial homolog of sodium/glucose transporters, which are membrane proteins that play a critical role in solute transport for a number of processes in the brain, intestines, and kidneys. To gain a better understanding of the role of vSGLT in the glucose transport cycle, it is important to capture the protein at each stage of transport: outward facing, closed and substrate bound, and inward facing. The structures for both the closed and inward facing conformations have been solved, but crystallizing the outward conformation has proven difficult.
In order to capture the last stage of the transport cycle, we will be working on expressing and purifying vSGLT mutants that will be probed for analysis via double electron-electron resonance (DEER) studies. This spectroscopic method reports on distance distributions between two probes that are selectively attached to engineered cysteine residues in the protein. Data from the DEER analysis will allow us to complete the picture of the transport cycle in vSGLT, which will ultimately expand our overall knowledge of glucose transport.
| Ms. Jessica Rodriguez
Pictured: Dr. Barney Schlinger, Jessica Rodriguez, and Dr. Michelle Rensel
Name: Jessica Rodriguez
Home University: UCLA
Faculty Mentor: Dr. Barney Schlinger
Jessica Rodriguez is a fourth year Neuroscience major at UCLA. She is currently working with Dr. Barney Schlinger and Dr. Michelle Rensel to investigate the role of neurosteroids on learning and memory in zebra finches.
Steroid hormones synthesized in the brain, known as neurosteroids, influence neuroplasticity and behavior, including learning and memory, as well as recovery from neural injury. In particular, estradiol has been identified as a neurosteroid affecting neuronal plasticity and thus may play a role in learning and memory. Neuroestrogens are produced from androgens by the enzyme aromatase that is expressed in the brain. In some songbirds, including zebra finches, aromatase is expressed at high levels in the hippocampus, a brain region crucial for vertebrate learning and memory.
The focus of Jessica's project is to determine whether performing a memory task regulates aromatase levels in the hippocampus via gene expression. Zebra finches are subjected to either a memory acquisition or a memory recall test that requires the localization of a food source in a four-armed maze. It is predicted that memory acquisition regulates aromatase via rapid modifications (i.e., phosphorylation of aromatase), while memory recall leads to longer-term regulation of gene expression. By performing behavioral assays, RNA extractions, reverse transcription, and quantitative polymerase chain reactions (qPCR), Jessica hopes to contribute to understanding the time course of aromatase expression and neuroestrogen production in the brain and their role in learning and memory.
| Ms. Christina Phuong
Pictured: Christina Phuong and Dr. Guillaume Chanfreau
Name: Christina Phuong
Home University: University of California, Los Angeles
Class: Third Year
Faculty Mentor: Dr. Guillaume Chanfreau
Christina Phuong is a third year UCLA student majoring in biochemistry. She works in the laboratory of Dr. Guillaume Chanfreau in the department of Biochemistry/Chemistry under the mentorship of graduate student, Cynthia Lee. Christina is currently investigating the role ART proteins play in the maintenance of homeostatic levels of metal ions, more specifically, iron and zinc ions, in the budding yeast, Saccharomyces cerevisiae.
Transition metals are factors essential to the survival of organisms; however, excessive amounts result in metal toxicity. In environments of high metal concentration, cells have adapted mechanisms to help maintain optimal intracellular concentrations of these metals. However, these mechanisms are not fully understood.
We hypothesize that Arrestin-related trafficking (Art) proteins are involved in metal transporter regulation, more specifically, the iron and zinc transporters, by targeting them for degradation. This hypothesis is drawn from previous research that has found that Art proteins, a class of nine adaptor proteins, help mediate ubiquitination and endocytosis by targeting plasma membrane proteins to the vacuole for degradation. In addition, levels of metal transporters have been shown to be regulated by endocytosis in high metal concentrations. Previous work has shown that yeast strains with mutated ART proteins display phenotypes different than the phenotype displayed by the wild-type strain in media containing high metal concentrations. These lines of evidence support the idea that Art proteins are involved in metal transporter regulation.
| Ms. Veronica Perez
Pictured: Dr. Margot Quinlan and Veronica Perez
Name: Veronica Perez
Home University: California State University of San Bernardino
Majors: Biochemistry and Biology Pre-Med
Faculty Mentor: Dr. Margot Quinlan
Veronica Perez attends Cal State San Bernardino and is double majoring in Biochemistry and Biology Pre-Med as she aspires to be a MD/PhD. She is a MARC Scholar and has been doing research in Dr. Laura Newcomb's Molecular Virology lab at her home university which focuses its research on the influenza A virus. Veronica aims to identify which influenza A mRNAs interact with nuclear export factor 1 (Nxf1) and exit the nucleus through the Nxf1 pathway and which do not. The influenza A mRNAs that are found to not exit via Nxf1 or the other defined pathway, Crm1, which is based on previous research, can be further studied to identify the as yet undefined nuclear export pathway, possibly revealing an atypical host pathway which could serve as a novel antiviral target against the virus.
During her stay at UCLA, Veronica worked in Dr. Margot Quinlan's Biochemistry Lab which studies the cytoskeleton in Drosophila. Veronica's project was to determine Cappuccino's (Capu's) biochemical interaction with actin filaments and microtubules. Her experimental aims were to determine if Capu, a protein, cross-links actin filaments and microtubules and to identify Capu's domain that mediates the interaction if cross-linking occurred. Her second experimental aim was to determine what happens when Capu, already bound to a growing actin filament, encounters a microtubule. These two experiments attempted to help build a model for how Capu coordinates microtubules and actin in oocytes. This can help in better understanding the role Capu's mammalian homologs play in human development and fertility.
| Mr. Harding Luan
Pictured: Dr. Ting-Ting Wu and Harding Luan
Name: Harding Luan
Home University: University of California, Los Angeles
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Ting-Ting Wu
Harding Luan is a rising junior at UCLA majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Since January 2011, he has been working as an undergraduate researcher under Dr. Ting-Ting Wu in the Department of Molecular and Medical Pharmacology. Dr. Wu is interested both in investigating mechanisms of gamma-herpesvirus infection and developing strategies against gamma-herpesviruses. Harding's efforts focus on developing a vaccine against gamma-herpesviruses.
The gamma subfamily of herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), is known for its ability to establish life-long infections that cause a variety of diseases, including a number of cancers, in immunocompromised patients. These diseases would best be prevented by an effective vaccine. Previous work using a murine homolog of KSHV and EBV has shown that a live-attenuated virus deficient in latency and multiple immune evasion genes is a safe and effective vaccine strategy. This set of mutations is necessary for the full efficacy of the virus, but introduce new challenges in regards to growing sufficient amounts of the virus when mirrored in KSHV because of the inability of KSHV to undergo efficient lytic infection in vitro. Harding's project moving forward will be to engineer a recombinant KSHV virus based upon the template of the effective murine homolog vaccine virus as well as develop a system in which to grow the vaccine virus efficiently. Successful establishment of this system will be an important step toward a possible preventative therapy for human gamma-herpesviruses.
| Ms. Michelle Lissner
Pictured: Dr. Stephen Smale and Michelle Lissner
Name: Michelle Lissner
Home University: UCLA
Major: Microbiology, Immunology, and Molecular Genetics
Faculty Mentor: Dr. Stephen Smale
Michelle Lissner is a senior at UCLA majoring in Microbiology, Immunology, and Molecular Genetics and minoring in Biomedical Research. She has worked in the lab of Dr. Stephen Smale in the Department of Microbiology, Immunology, and Molecular Genetics since her sophomore year. Michelle's current project examines changes in immune system function at different stages of life.
Deficiencies in the immune systems of newborns, pregnant women, and the elderly lead to susceptibility to a variety of intracellular pathogens. Part of this increased vulnerability in newborns is caused by an impaired ability to mount T helper (Th) 1 immune responses. Efficient responses from adult Th1 cells lead to cell-mediated immunity though the activation of phagocytes and the release of cytokines. Data suggest that the defect in newborn Th1 response is due to the reduced activation of genes dependent on interferon regulatory factor 3 (IRF3).
Michelle is using RNA-Seq to characterize the transcriptional program of newborn, adult, and elderly peripheral blood monocytes in response to infection by Listeria monocytogenes, an age-dependent intracellular pathogen. This project will both identify subsets of genes that are differentially regulated throughout the life cycle as well as provide new insights into the mechanisms controlling expression of these genes.
| Mr. Richard Li
Pictured: Richard Li and Dr. Thomas Graeber
Name: Richard Li
Home University: Stanford University
Major: Chemical Engineering
Faculty Mentor: Dr. Thomas Graeber
Richard is a third-year Chemical Engineering major at Stanford University, where he conducts research in RNA interference resistance mechanisms under the auspices of Dr. Andrew Fire. At UCLA, Richard works in Dr. Graeber's laboratory in the Department of Molecular & Medical Pharmacology.
Richard's work focuses on aberrant melanoma cells that have acquired resistance to PLX4032, a recently FDA-approved cancer treatment hailed as one of the first successful gene-targeted therapeutics. Although treatment with PLX4032 significantly reduces tumor size and extends life expectancy, melanoma cells invariably become resistant to therapy after only six months, on average.
Previous studies have shown that these resistant cell lines exhibit an invasive phenotype-switch phenomenon, requiring focal adhesion processes to maintain resistance. Richard's studies aim to elucidate the mechanisms governing this resistance by targeting RTK-signaling of the RAS-ERK and PI3K-AKT survival pathways. Extracellular matrix components and growth factors may also play a role in inducing resistance. Ideally, a clearer understanding of these resistance mechanisms can give rise to further drug developments that target several aberrant targets along the signaling pathway, the combination of which may counteract drug resistances that arise.
| Mr. Ben Leiken
Pictured: Ben Leiken and Dr. Christopher Colwell
Name: Ben Leiken
Home University: Tufts University
Major: Computer Science
Faculty Mentor: Dr. Christopher Colwell
Ben is a Computer Science major from Tufts University in Massachusetts. His previous research, conducted at Children's National Medical Center in Washington, DC under Drs. Eric Hoffman and David Rowlands, involved using systems biology and statistics to uncover the genetic pathways behind skeletal muscle remodeling.
Ben's research at UCLA involves utilizing video analysis to evaluate the sleep/wake behavior of mice afflicted with Huntington's Disease (HD). HD is caused by an excess of CAG repeats on the Huntingtin gene on chromosome 4. The disease is inherited, but patients often go decades before cognitive symptoms present themselves. The most common and familiar symptoms of Huntington's are involuntary movements, known as chorea, and difficulty with motor coordination. Other features of the disease can include depression, cognitive deficits, and sleep disturbances. Sleep disturbances have detrimental effects on the daily functioning of Huntington's patients. Because these patterns of sleep disturbances arise early on in the progression of the disease, an understanding of the mechanism behind them could allow for an earlier diagnosis and improved treatment of HD. Dr. Colwell's lab has found evidence that a disruption in the circadian system is a contributing factor.
Ben hopes to elucidate whether the mouse model of HD exhibits changes in circadian rhythms, as measured by altered sleep/wake behavior. His work will help to determine how the degeneration of circadian rhythms in the mouse model compares with those of human Huntington's patients. Ben also hopes to develop and refine a superior method for performing video analysis of mouse behavior.
| Mr. Robert Lamm
Pictured: Bob Lamm and Dr. Daniel Kamei
Name: Robert Lamm
Home University: University of California, Los Angeles
Faculty Mentor: Dr. Daniel Kamei
Bob Lamm is a fourth year bioengineer at UCLA and works in the laboratory of Dr. Daniel T. Kamei. Bob is currently working on improving chemotherapeutic drug delivery for the treatment of prostate cancer using the A11 minibody.
Prostate cancer is the most common cancer in men in the US, with approximately 240,000 men expected to be diagnosed this year. Current chemotherapeutic treatments are highly non-specific, causing toxic side effects. They can be improved, however, by adding passive and active targeting. The result is a treatment with increased efficacy and decreased toxicity.
Polymeric nanoparticles made of poly(lactic-co-glycolic acid) (PLGA) have been investigated for several years for their ability to encapsulate drugs. Encapsulation provides protection from the in vivo environment, as well as passive targeting through the enhanced permeability and retention (EPR) effect. Nanoparticles have been loaded with the small molecule drug doxorubicin (DOX) to some success, but these systems can be improved with specific targeting.
The A11 minibody was developed by the lab of Dr. Anna Wu in the department of Molecular and Medical Pharmacology at UCLA as a positron emission tomography imaging agent for prostate cancer. The minibody exhibits an extremely high binding affinity for the prostate stem cell antigen, which is overexpressed in prostate cancer cells. This is the first investigation of using A11 to target chemotherapeutics to prostate cancer. Specifically, Bob's goal is to demonstrate that drug-loaded nanoparticles conjugated to A11 will exhibit enhanced drug delivery compared to non-targeted, drug-loaded nanoparticles.
| Mr. Vincent Heng
Front row: Jianqiao Huang, Michael Nayhouse, Vincent Heng, Professor Gerassimos Orkoulas, Sangil Kwon
Back Row: Liangfeng Lao, Tung-Sheng Tu
Name: Vincent Heng
Home University: UCLA
Major: Chemical Engineering
Faculty Mentor: Gerassimos Orkoulas
Vincent is a senior at UCLA studying Chemical Engineering with a focus on Biomolecular Engineering. He has been working with Professor Gerassimos Orkoulas' Molecular Simulation Laboratory for over a year. Currently, Vincent has been simulating the crystallization of proteins using the Grand Canonical Monte Carlo Method over a range of potentials such as the Lennard-Jones. By simulating fluid-solid coexistence in proteins, coexistence pressures and temperatures can be explicitly found to assist in batch crystallization, and phase diagrams for different protein systems are developed.
Although fluid-fluid transitions have been simulated precisely, fluid-solid freezing transitions remains a difficult task. Currently, the Molecular Simulation Laboratory is using the constrained cell model developed by Hoover and Ree to simulate this transition. The constrained cell model places each particle into its own Wigner-Seitz cell. This model is a limiting case of a more general cell model that is constructed by adding an external field to control the relative stability of the two phases. Simulations are done at constant pressure and show continuous behavior at low pressures and discontinuous jumps at high pressure. The pressure where the continuous and discontinuous jump occurs is close to the mechanical stability point of the solid phase. Size dependent coexistence pressures and densities are analyzed according finite-size scaling techniques for first-order phase transitions to show the importance for accounting for size effects in simulation of fluid-solid transitions. This research is the first step to assist in many protein crystallization processes.
| Mr. James Hedrick
Pictured: Dr. Heather Maynard and James Hedrick
Name: James Hedrick
Home University: Massachusetts Institute of Technology
Major: Biological-Chemical Engineering
Faculty Mentor: Professor Heather Maynard
James has performed research at multiple Universities in a diverse set of areas. Research in functionalizing gold nanoparticles for therapeutic uses was performed under the direction of Professor Baroli at University of Cagliari. At Stanford University he performed research in the area of Carbon Nanotubes (CNTs) sorting, purification, assembly and devices in the Bao Lab, Department of Chemical Engineering. At Massachusetts Institute of Technology, his home university, he has researched drug and gene delivery for cancer research in the Hammond Lab, Department of Chemical Engineering. He also performed organ transplantation and gene therapy research at Imperial College under the direction of Professor George, Department of Immunology.
At UCLA, James is researching trehalose-based polymers as a technique to stabilize therapeutic proteins for transport and delivery in the Maynard Group, Department of Biochemistry and Chemistry. With protein therapy becoming a more prominent treatment for diseases, there is a need to fabricate medicine with higher pharmacokinetic properties. One way to increase proteins is to create a protein polymer conjugate. Increasing the stability of a protein will decrease the necessary dosage for patients, and potentially the dosage frequency as well. Hence, there is an increasing demand for proteins stable to thermal fluctuations, enzymatic activity, freeze-thawing, and other stressors for application in a variety of therapies.
The proposed study is to synthesize two glycopolymers and to analyze their toxicity to cells. Results of the proposed studies will give insight into trehalose glycopolymer efficacy as a conjugate, as well as its potential cytotoxicity.
| Ms. Vira Fomenko
Pictured: Vira Fomenko, Dr. Michael S. Levine, and Anna Parievsky
Name: Vira Fomenko
Home University: University of California, Santa Barbara
Faculty Mentor: Dr. Michael S. Levine
At UCSB, Vira studied the effects of preexisting attentional abilities on novel motor task performance and the corresponding changes in brain activity using electroencephalography (EEG) in Dr. Giesbrecht's Attention Lab. She has also worked at Dr. Ettenberg's Behavioral Pharmacology Lab, studying the neural pathways associated with the dual effects, immediate euphoric and delayed anxiogenic, of cocaine. Next year, Vira's senior thesis will focus on elucidating the relationship between the magnitude of first-time user's anxiogenic effects and the likelihood of developing cocaine addiction.
This summer, Vira is studying neuronal changes underlying Huntington's disease (HD) under the guidance of Dr. Michael Levine and graduate student, Anna Parievsky, at UCLA's Department of Psychiatry and Behavioral Sciences.
A fatal neurodegenerative disorder, HD is neuropathologically characterized by a severe loss of striatal medium-sized spiny neurons (MSNs), which receive mainly cortical and thalamic glutamatergic inputs. Electrophysiologically studied cortical inputs have been shown to cause biphasic changes, such as early increases and late decreases in MSN activation during HD.
This summer, Vira will characterize the physiology of thalamostriatal inputs and compare them to corticostriatal using optogenetics. She will use an adeno-associated virus (AAV) to express optically active cation channels, channelrhodopsin-2 [ChR2(H134)], and yellow fluorescent proteins (YFP), in either the cortex or thalamus of either wildtype or R6/2 (rapidly progressing HD model) mice. Vira will use light to selectively activate ChR2 expressing projections from either the cortex or thalamus in order to electrophysiologically measure changes in membrane potentials and determine the HD-related changes in those MSN inputs.
| Mr. Michael Erb
Pictured: Dr. Manuel Penichet, Michael Erb, and Dr. Tracy Daniels
Name: Michael Erb
Home University: Claremont McKenna College
Faculty Mentor: Dr. Manuel Penichet
At Claremont, I study the chromatin remodeler CHD1 in Drosophila under the direction Dr. Jennifer A. Armstrong and serve as a captain on the baseball team.
This summer I am working in Dr. Manuel Penichet's lab under the mentorship of Dr. Tracy Daniels. The lab focuses on immunotherapeutic approaches to create novel cancer therapies. Previously, the lab created an antibody-avidin fusion protein as a universal vector to deliver biotinylated compounds into cancer cells. This fusion protein, ch128.1Av, is composed of a chimeric antibody genetically fused to chicken avidin. It is specific for and brought into the cell by the transferrin receptor, which is overexpressed on cancer cells. Using the high affinity of avidin for biotin, the biotinylated plant toxin saporin 6 can be conjugated to the fusion protein, and the antibody can deliver the toxin to cancer cells. The fusion protein alone possesses inherent cytotoxicity to certain malignant B-cells, allowing for a targeted, two-pronged attack.
My work in Dr. Penichet's lab has two focuses. The first is to evaluate the cytotoxic effect of the conjugate in mantle cell lymphoma cell lines, a type of malignant B-cell that has not yet been tested. The next is to help elucidate the mechanism of cell death induced by saporin delivered into cancer cells. To do this, I will work to confirm previously found gene expression changes in cancer cells treated with the conjugate. I will also explore the possible induction of reactive oxygen species by saporin as an indirect cause of DNA damage.
| Mr. Sai Devana
Pictured: Sai Devana, Dr. Dwayne Simmons, and Aubrey Hornak
Name: Sai Devana
Home University: UCLA
Major: Molecular Cellular and Developmental Biology
Faculty Mentor: Dr. Dwayne Simmons
Age-related hearing loss or presbyacusis, affects about 1/3rd of adults over the age of 65. Although the mechanisms of presbyacusis are not completely understood it is known to involve the sensory cells of the inner ear. The function of the mammalian auditory system depends upon fundamental mechanisms found in these sensory cells, the outer hair cells (OHCs) and the inner hair cells (IHCs) of the cochlea. Although the IHCs are responsible for sending acoustic information to the brain via afferent pathways, OHCs act as mechanosensors that amplify mechanical responses to sound and give rise to the exquisite sensitivity and frequency selectivity of mammalian hearing. OHCs depend on the tight regulation of Ca2+ for their function and survival. A lack of regulation of cytosolic [Ca2+]i could lead to OHC dysfunction, cell loss and eventual hearing impairment. Although there are a host of Ca2+ pumps and ion channels that a capable of regulating cytosolic [Ca2+]i, we know the least about the role of calcium-binding proteins (CaBPs). Unlike IHCs, OHCs express a specific CaBP, oncomodulin (Ocm) that may be especially tailored to the unique function of OHCs. 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 OHCs as a buffer. By regulating intracellular calcium, Ocm could have large implications in stress responses, motility, and progressive hearing loss.
| Ms. Cameron Curtin
Pictured: Dr. Neil Harris and Cammie Curtin
Name: Cameron (Cammie) Curtin
Home University: Middlebury College
Faculty Mentor: Dr. Neil Harris
Cammie is heading into her last semester at Middlebury College, in Vermont. There, she majors in neuroscience, while also taking full advantage of the liberal arts offerings. At Middlebury, she has worked with Dr. Mark Stefani, investigating the ability of positive GABA modulation to attenuate cognitive deficits in a rat model of schizophrenia. She also serves as an associate editor for IMPULSE, an online undergraduate journal of neuroscience.
This summer, Cammie has joined the lab of Dr. Neil Harris, which explores cortical plasticity after traumatic brain injury (TBI). Central nervous system (CNS) neurons do not undergo spontaneous axon regeneration after injury, leading to poor CNS recovery. Thus, in order to develop effective TBI treatments, strategies to promote axonal outgrowth after injury must be identified. Rolipram, a drug that inhibits phosphodiesterase breakdown of cyclic adenosine monophosphate (cAMP), has been shown to enhance regeneration after CNS damage. However, a recent study using a fluid percussion model of TBI suggests that rolipram may in fact exacerbate brain injury, increasing contusion volume. To better assess rolipram's potential as a TBI treatment, it is necessary to study its effects after injury using controlled cortical impact (CCI), a TBI model that produces a more focused and controlled injury than fluid percussion. Currently, Cammie is investigating the effects of rolipram on contusion volume and axonal sprouting after CCI. Her study will assess whether or not rolipram exacerbates cortical injury and, for the first time, examine the effects of positive cAMP regulation on axonal regeneration after CCI.
| Ms. Nicole Cremer
Pictured: Nicole Cremer and Dr. Isaac Yang
Name: Nicole Cremer
Home University: UCLA
Faculty Mentor: Dr. Isaac Yang
Nicole is entering her third year as a Neuroscience major at UCLA. She works in Dr. Isaac Yang's laboratory in the UCLA Neurosurgery Brain Tumor Nanotechnology Institute. Nicole's project evaluates the anti-tumor antibody response to CD 133+ cells from glioma cell lines in vitro.
Glioblastoma multiforme is the most common primary malignant brain tumor in adults. Despite advances in treatment for glioblastoma multiforme, including surgical resection, radiation therapy and chemotherapy, the prognosis remains dismal. Therefore, new strategies that effectively target tumors and reduce their spread are necessary. One strategy that is gaining popularity is inducing antitumor immunity through dendritic cell vaccines. Dendritic-based immunotherapy delivers dendritic cells loaded with tumor antigens to stimulate an antigen-specific-T-cell-mediated antitumor response.
To maximize the potential of an effective cancer vaccination strategy, the choice of tumor antigens and antigen presentation to the immune system must be critically evaluated. CD 133+ is a stem cell-like subpopulation that was recently identified in glioblastoma multiforme. Nicole's project evaluates the efficacy of using CD 133+ glioma cell lysate-pulsed dendritic cell therapy. The goal of Nicole's project is to show that this vaccine will invoke a superior anti-tumor response associated with longer survival, slower tumor growth, increased tumor-infiltrating lymphocytes, and reduction in CD133+ tumor subpopulation in order to demonstrate that a dendritic cell vaccine comprising dendritic cells pulsed with CD133+ glioma cell lysate may provide a safe and effective therapy that utilizes the patient's own immune system to selectively target the highly tumorigenic CD133+ glioma subpopulation.
| Mr. Jang (John) Cho
Pictured: Dr. Robert Clubb and Jang (John) Cho
Name: Jang (John) Cho
Home University: Carleton College
Faculty Mentor: Robert T. Clubb
John is a rising junior at Carleton College and is majoring in Chemistry with a minor in Biochemistry. At Carleton, he has worked in an Immunology lab under Dr. Debby Walser-Kuntz where he studies in vivo effects of bisphenol A (BPA) on CXCL1 and PGE2 level in mouse immune system. The FOXP3 gene expression level in T cells among BPA-fed mouse is under investigation to determine if BPA actively induces Treg response via PGE2.
At UCLA, John is studying the function of N-terminus appendage found in Ba-SrtA, a sortase enzyme from Bacillus anthracis, under Dr. Robert Clubb and Alex Jacobitz in the Department of Chemistry & Biochemistry. Sortase is a Gram-positive bacterial enzyme which anchors surface proteins to peptidoglycan cell wall. Surface proteins mediate microbial adhesion to host tissues, suppression of the immune system, and acquisition of essential nutrients. Therefore, targeting sortase has been considered an effective strategy for developing anti-infective molecules. Previous findings suggested that this N-terminal tail, in conjunction with a flexible active site loop (β7/β8), mediate the recognition of lipid II, the second substrate of sortase during anchoring of surface proteins. To examine the role of the appendage, several amino acids in the tail region will be mutated. After confirming that the appendage is essential for anchoring surface proteins, we will examine if the appendage mediates the LPXTG sorting signal or the lipid II.
| Mr. Hunter Bennett
Pictured: Miguel Lopez, Hunter Bennett, Dr. Kent Hill, Ed Saada
Name: Hunter Bennett
Home University: University of Washington
Faculty Mentor: Dr. Kent Hill
Hunter Bennett is a rising junior at the University of Washington. He is majoring in Bioengineering with a minor in Chemistry. At UW Hunter works under Dr. Kim Woodrow in the Department of Bioengineering developing a cell-based therapeutics for preventing HIV transmission. At UCLA he is working in the Department of Microbiology, Immunology and Molecular Genetics with Miguel Lopez in the lab of Dr. Kent Hill. His work is focused on understanding social motility and social behavior in Trypanosoma brucei.
Trypanosoma brucei cause Human African trypanosomiasis, or African sleeping sickness, a deadly disease affecting humans and animals that limits economic growth in some of the poorest countries in Sub-Saharan Africa. If a T. brucei population is plated on semisolid agarose, communities of cells divide and migrate outward along the gel to form fingerlike radial projections from their initial position. While the movement of radial projections has been well documented, the initial formation of fingers and the density dependent characteristics of the movement are poorly understood. By studying early phase social behavior at a variety of cell densities we hope to gain a better understanding of the rules governing the interactions between communities of T. brucei. Furthermore, a fuller understanding of social behavior in T. brucei will aid analysis of RNAi knockdowns and subsequent identification of compounds key to social behavior.
Hunter would like to thank the Hill lab, the Amgen Foundation and the program faculty at UCLA for the chance to participate in such captivating full time research.
| Ms. Ashley Bauer
Pictured: Dr. Kin Sui, Ashley J. Bauer, and Dr. Linda Cai
Name: Ashley J. Bauer
Home University: University of Minnesota Duluth
Major: Cell and Molecular Biology
Faculty Mentor: Dr. H. Linda Cai
I am a rising senior majoring in Cell and Molecular Biology at the University of Minnesota Duluth. In my first lab in Duluth, I worked with Dr. Jeffrey Gilbert on examining the potential therapeutic role of exercise on pregnancy-induced hypertension. In my current lab in Duluth, I am working with Dr. Jean Regal on the role of the complement system in pregnancy-induced hypertension. This summer at UCLA, I am working with Dr. Linda Cai in the Department of Anesthesiology. The purpose of my summer project is to examine the molecular mechanisms underlying abdominal aortic aneurysm formation.
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) protects vascular health. eNOS requires its cofactor tetrahydrobiopterin (H4B) to produce NO. If H4B becomes deficient, eNOS will become dysfunctional and produce superoxide rather than NO, promoting vascular dysfunction. This is known as eNOS uncoupling and may play a significant role in the development of abdominal aortic aneurysms (AAA). Vascular remodeling during AAA formation is believed to involve matrix metalloprotease (MMP) release. Although it has been shown that pathologically uncoupled eNOS results in excessive hydrogen peroxide, the signaling pathway that leads from H4B deficiency to MMP activation remains unclear. Therefore, it is hypothesized that hydrogen peroxide plays an important role in the pathway between eNOS uncoupling consequent to H4B deficiency and endothelial cell MMP activation. By better understanding the molecular mechanisms underlying AAA formation, novel therapies targeting these mechanisms can be developed for AAA, where treatment options are extremely limited.