2011 UCLA Amgen Scholars Program

Student Profiles

Ms. Julia Arzeno

Ms. Emily Brown

Ms. Kerensa Crump

Mr. Jonathan Diep

Mr. Michael Einstein

Ms. Katerina Korch

Mr. Kevin Kowalski

Ms. Jennifer Kuo

Mr. Andy Chao Hsuan Lee

Ms. Christina Liu

Mr. Gabriel Loewinger

Ms. Edna Miao

Ms. Eva Morozko

Mr. Takahiro Ohara

Ms. Katrina Owens

Mr. Aanand Patel

Mr. Erik Reinertsen

Ms. Christine Ryan

Ms. Sandra Sanchez

Ms. Cindy Schmelkin

Mr. Joseph Vella

Mr. Christopher Wei

Ms. Ahuva Weltman

Ms. Jamie Yao

Name: Julia Arzeno
Home University: University of California, Los Angeles
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Michael Teitell

Pictured: Dr. Jessica Fowler, Julia Arzeno, and Dr. Michael Teitell

Julia is entering her fourth year as a Molecular, Cell, and Developmental Biology major at UCLA. She works in Dr. Michael Teitell's laboratory in the Department of Pathology and Laboratory Medicine. Under the guidance of the postdoctoral fellow, Dr. Jessica Fowler, Julia is studying the role of lipid metabolism in B cell development.

B cells are lymphocytes that play an important role in the antibody-mediated immune response. Recent studies have identified a novel signal transduction pathway that is activated in differentiating GC B cells. This pathway regulates 136 genes, one of which is the ATP-binding cassette transporter ABCA1, a membrane protein that controls cholesterol efflux from cells and that is functionally associated with B cell activation. To examine the role of lipid metabolism in B cells, a plasmid vector will be constructed to knockdown ABCA1 expression and allow for subsequent phenotypic characterization of the knockdown in B cells. Because ABCA1 plays a role in cholesterol efflux from cells, knockdown is expected to raise the intracellular lipid content, increasing membrane fluidity. If this altered membrane composition results in the generation of more lipid rafts, and if those rafts act to increase BCR micro cluster formation, the knockdown would be expected to increase BCR signaling, producing an activated B cell.

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Name: Emily Brown
Home University: Massachusetts Institute of Technology
Major: Biological Engineering
Faculty Mentor: Dr. Otto Yang

Pictured: Justin De La Cruz, Dr. Otto Yang, and Emily Brown

Emily Brown is a third year undergraduate majoring in Biological Engineering at MIT. Since January 2010, she has worked under Dr. Shuguang Zhang in the MIT Center for Biomedical Engineering, synthesizing olfactory receptor molecules used to bind odorants and testing the expression of these molecules in cell-free systems. As part of a team, she has created designer lipid-like peptides that solubilize and stabilize olfactory receptors.

At UCLA, Emily is researching HIV-1 escape mutations under Dr. Otto Yang in the Department of Medicine. Cytotoxic T lymphocytes (CTLs) activated soon after infection suppress HIV-1 and limit its spread by binding to HIV-1 infected cells and inducing cell lysis. This suppression is incomplete, for HIV-1 can quickly develop epitope escape mutations, which decrease the ability of the CTLs to recognize and bind to HIV-1 infected cells. These mutations, however, often have a fitness cost which reduces the survival of the virus. Emily is identifying viral escape mutations in acute HIV-1 infection in one individual, GWR and quantitatively measuring the fitness costs of these mutations. Her goal is to find what factors cause viral escape in early infection, for the ultimate purpose of developing a CTL-targeted HIV-1 vaccine.

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Name: Kerensa Crump
Home University: State University of New York - Binghamton
Major: Neuroscience; Biochemistry
Faculty Mentor:
Dr. Carlos Portera-Cailliau

Pictured: Dr. Ricardo Mostany, Kerensa Crump, and Dr. Carlos Portera-Cailliau

Kerensa Crump is a rising junior at Binghamton University and is double majoring in Neuroscience and Biochemistry. At BU she works in a behavioral neuroscience lab under Terrence Deak where they study the intracellular mechanisms of HPA-axis mediated stress responses. This summer, she is working with Ricardo Mostany in Carlos Portera-Cailliau’s neurobiology lab, which uses cutting-edge advances in the application of two-photon excitation microscopy to in vivo imaging, in order to investigate the detailed plasticity and structure of neurons. Currently, she is working on a hypothesis of small-scale structural correlates of aging.

The strength of glutamatergic synapses is directly related to the number of AMPA receptors present on each dendritic spine. As receptors are upregulated, the volume increases and the spine usually develops a characteristic mushroom shape, while low-volume thin and stubby spines have far fewer AMPA receptors. Bouton size is directly related to synaptic strength as well. The importance of increased synaptic strength is that it produces long-term potentiation and thus facilitates learning and memory. If synaptic strength is lessened by an increase in the prevalence of low-volume spines and boutons, it is possible that this could contribute to the cognitive decline seen in aging.

This hypothesis is being investigated using chronic imaging of transgenic mice expressing GFP in select neurons in layer 1 of the cortex. Mouse craniotomies are followed by the application of a clear plastic “window” that allows GFP excitation with two-photon excitation microscopy and subsequent image analysis using Matlab software.

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Name: Jonathan Diep
Home University: University of California, Los Angeles
Major: Microbiology, Immunology, and Molecular Genetics
Faculty Mentor: Dr. Ren Sun

Pictured: Dr. C. Anders Olson, Jonathan Diep, and Dr. Ren Sun

Jonathan Diep is in his third-year at UCLA, majoring in Microbiology, Immunology, and Molecular Genetics with a minor in Biomedical Research. Since March 2010, he has been an undergraduate researcher in Dr. Ren Sun’s laboratory in the Department of Molecular and Medical Pharmacology. Working alongside Dr. C. Anders Olson, Jonathan has been exploring the use of mRNA display selection as a rapid, high-throughput screen to evolve antibody-like fibronectins that could represent novel alternatives to commercial antibodies.

Antibodies naturally help the immune system fight off infections, but they have also become powerful tools for biological research. A major drawback, however, is that antibody production is both time-consuming and expensive. mRNA display selection is an in vitro high-throughput screening technique that can rapidly evolve antibody-like molecules, bypassing the immune response that is required to generate antibodies. Novel, antibody-like fibronectins, with targets ranging from human interleukin-6 to the nucleocapsid protein of the severe acute respiratory syndrome coronavirus, were rapidly evolved by mRNA display selection. These fibronectins have been shown to function like antibodies in vivo, and Jonathan’s project is to demonstrate that they also capture and detect their targets in vitro in enzyme-linked immunosorbent assays (ELISAs) and western blots. He will design bacterial expression vectors with conjugations to alkaline phosphatase and horseradish peroxidase, and after expressing and purifying the protein-fusion constructs, Jonathan will optimize conditions for their performance on ELISAs and western blots. The ability to rapidly generate antibody-like molecules would have far-reaching implications in research, from molecular biology to therapeutics and diagnostics.

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Name: Michael Einstein
Home University: Carleton College
Major: Biology
Faculty Mentor: Dr. Nicholas Brecha

Michael Einstein is a biology major at Carleton College. At UCLA, he is studying intercellular communication within the retina in the Brecha lab.

In the retina, dopaminergic amacrine cells (DA cells) release dopamine to modulate a variety of responses to light. In particular, DA cells interact with intrinsically photosensitive retinal ganglion cells (ipRGC’s), which play a major role in determining circadian rhythms. While there is significant evidence for this interaction, less is known about the modulatory inputs to DA cells.

Somatostatin (somatotropin release-inhibiting factor, SRIF) –containing amacrine cells may provide modulatory input to DA cells. These cells exhibit similar physiological responses to light as other neurons responsible for sensing night and day. Additionally, the Brecha lab has generated preliminary results showing dendrites from each cell type associating within sublamina 1 of the inner plexiform layer. Michael’s project will expand on this anatomical data using immunohistochemistry on rat retinas.

Studying the interaction between DA cells and SRIF-containing amacrine cells is important not only for understanding the regulation of circadian rhythms, but also for developing models of intercellular circuitry within the central nervous system. Understanding circuits in the retina may serve as a basis for understanding more complex circuits in the cortex and other brain areas.

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Name: Katerina Korch
Home University: Juniata College
Major: Chemistry
Faculty Mentor: Dr. Craig Merlic

Pictured: Dr. Craig Merlic, Katerina Korch, and graduate student Tioga Martin

Katerina Korch is a fourth year chemistry major at Juniata College in Huntingdon, Pennsylvania. At UCLA she is investigating copper(II)-promoted couplings of vinyl boronates and alcohols to form vinyl ethers with the guidance of Dr. Craig Merlic and graduate student Tioga Martin.

Vinyl ethers are important precursors for the Claisen rearrangement; however, they are deceptively difficult functional groups to synthesize. Previous attempts have relied on the use of strong acids or bases, toxic metals, or reactive nucleophiles which limits the substrates that can be used. Recent work in the field of copper(II)-promoted couplings has provided a new, mild means to synthesize vinyl ethers. This method relies on the use of a vinyl pinacol boronate ester, an excess of alcohol, two equivalents of copper(II) acetate, and an alkyne ligand. This reaction proceeds under ambient atmosphere at room temperature, and it produces reasonable yields of the vinyl ether for several combinations of substrates. However, several improvements can still be made to optimize the reaction conditions.

Current investigations are directed toward screening alternative ligands in order to determine if yields of certain substrates can be increased. Other investigations are directed toward optimizing the reaction conditions to be stoichiometric in respect to both the vinyl boronate and alcohol coupling partners, and exploiting the catalytic potential of the reaction in order to reduce the amount of copper necessary.

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Name: Kevin Kowalski
Home University: California Institute of Technology
Major: Mathematics; Computer Science
Faculty Mentor: Dr. Rob Suh

Pictured: (Back Row) Dr. Lakshminarayan Srinivasan, Dr. Fereidoun Abtin, (Front Row) Dr. Rob Suh, and Kevin Kowalski

Kevin Kowalski is a senior studying math and computer science at Caltech. He is working with Dr. Lakshminarayan Srinivasan of UCLA to produce a theoretical model of co-adaptive learning in brain-computer interfaces.

The study of brain-computer interfaces is an emerging field that has great potential to improve quality of life in disabled patients. In amputee patients, for example, a prosthetic replacement that could be controlled with brain signals alone would provide a significant functional improvement over completely mechanical prostheses. A fundamental problem in the design of these interfaces, though, is that of how to decode the intended movement of a prosthetic device from neuronal firing information alone; while a human subject can eventually learn to tune the firing of individual neurons to control a static decoder, researchers have developed adaptive decoders that can make successively better estimates of a subject's intention, allowing subjects to achieve more accurate control more quickly.

While some theoretical framework exists for modeling the interaction between human and computer here, it typically assumes that only one of the two is learning at any time. In particular, there is no model that allows the human and computer to adapt to each other simultaneously, something termed “co-adaptive learning.” Kevin's project is to create this model and to verify its predictions through experiments with human subjects. This study will give researchers a better understanding of the dynamics of co-adaptive learning, and will better allow them to validate their algorithms without the expense of human experimentation in the future.

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Name: Jennifer Kuo
Home University: University of California, Los Angeles
Major: Molecular, Cell, Developmental Biology
Faculty Mentor: Dr. Lily Wu

Pictured: Karen Jiang, Jennifer Kuo, and Dr. Lily Wu

Jennifer Kuo is a third year Molecular, Cell, and Developmental Biology major with a minor in biomedical research. Under the direction of Dr. Lily Wu and the mentorship of Karen Jiang, Jennifer is evaluating the efficacy of androgen blockade therapy in prostate cancer with a functional androgen receptor reporting system.

Because prostate cancer cells rely on the androgen receptor (AR) signaling axis for proliferation, the first line of prostate cancer treatment comprises 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 neither ADT nor ARBT preventing cancer progression despite ostensible androgen blockade. Recent studies suggest 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.

Jennifer would like to thank the Wu lab for their help and guidance, and the Amgen Foundation for their generous support.

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Name: Andy Chao Hsuan Lee
Home University: University of California, Los Angeles
Major: Bioengineering
Faculty Mentor: Dr. Dino Di Carlo

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.

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Name: Christina Liu
Home University: University of California, Los Angeles
Major: Bioengineering
Faculty Mentor: Dr. Daniel Kamei

Christina Liu is a fourth year bioengineer at UCLA and works in the laboratory of Dr. Daniel T. Kamei. She is currently developing gold nanoparticles (AuNPs) for the targeted delivery of cancer therapeutics.

Transferrin (Tf) has been widely used as a targeting agent for cancer therapy, since its receptors are overexpressed by many cancers. However, the short residence time of Tf in the cell limits its therapeutic efficacy. To increase the probability of Tf delivering its payload, previous lab members developed Tf variants with an increased cellular association and showed that they were more effective drug carriers compared to native Tf.

While Tf-drug molecular conjugates are promising for cancers treated locally, they cannot be delivered systemically due to competition from endogenous Tf. Since a less invasive, systemic administration of a drug is preferred for most cancers, there is a need for a different carrier system. AuNPs are one such class of therapeutics that can passively target tumors via the enhanced permeability and retention effect. Cellular uptake and specificity can be further enhanced by conjugating targeting ligands such as Tf onto the surface of the AuNP. Since AuNPs are biocompatible, stable, and can bind to proteins via dative bonds, they are an attractive drug carrier for the systemic delivery of protein toxins such as diphtheria toxin. The goal of Christina’s project is to demonstrate that, similar to the molecular conjugates, AuNPs conjugated to the Tf variants will exhibit a greater cellular association and enhanced drug delivery compared to their native counterparts.

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Name: Gabriel Loewinger
Home University: Pitzer College
Major: Neuroscience
Faculty Mentor: Dr. Nigel Maidment

Pictured: Dr. Sean Ostlund, Dr. Nigel Maidment, Gabe Loewinger, and Dr. Kate Wassum

Gabe is primarily interested in studying chemical dependence through the lens of behavioral neuroscience and neuropharmacology. In the past, Gabe conducted his most focused research at Dr. Joe Cheer’s lab at the University of Maryland, Medical School, in Baltimore, where he studied how the endocannabinoid system modulates methamphetamine neurotoxicity in the mesolimbic dopamine system.

At UCLA, Gabe is using electrochemical techniques to understand how the neurotransmitter dopamine is involved in the production of reward-seeking actions in responses to cues associated with reward. By elucidating how animals learn about the relationship between rewards and cues, the lab gains insight into compulsive disorders where cues exert excessive control over behavior, as is the case in drug addiction and compulsive gambling. Understanding the neural correlates responsible for such behavior allows for the targeted development of therapeutics aimed at treating impulse control disorders.

The Maidment lab employs fast scan cyclic voltammetry to investigate dopamine release dynamics in freely-moving rats in an operant and Pavlovian behavioral paradigm, entitled Pavlovian-to-Instrumental transfer. This technique allows the detection of dopamine on a subsecond time scale to temporally resolve the nature of its release patterns in behaving animals. The lab is specifically concerned with how this neurotransmitter is involved in the production of goal-directed actions in response to cues that predict reward. Through sophisticated behavioral paradigms, the lab hopes to dissociate two types of conditioning, Pavlovian and instrumental, and investigate the role of dopamine in these types of learning.

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Name: Edna Miao
Home University: University of California, Los Angeles
Major: Microbiology, Immunonology, & Molecular Genetics
Faculty Mentor: Dr. Samuel French

Pictured: graduate student Ronik Khachatoorian, Edna Miao, and Dr. Samuel French

Edna Miao is a junior in the department of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles. She works in the laboratory of Dr. Samuel French in the department of pathology and laboratory medicine. In collaboration with graduate student Ronik Khachatoorian, Edna is currently investigating the interactions between hepatitis C viral protein NS5A and host proteins Hsp70 and Hsc70.

NS5A is necessary for virus replication and virion assembly, and is organized into three domains. Many host factors, such as cellular heat-shock proteins, are also required for virus production. Heat shock proteins (HSPs) are important during the cellular stress response, and are responsible for refolding polypeptide chains. NS5A and Hsp70 interact to form a NS5A/Hsp70 complex necessary for viral production. The site of interaction on Hsp70 is not yet known; however, it appears to be localized to the N-terminal nucleotide-binding domain. Edna will be utilizing GST pull-down assays and western blot analysis to identify the precise identification of this site on Hsp70, in order to elucidate the mechanism of NS5A-driven IRES-mediated translation. The same methods will be applied to the highly homologous heat shock cognate protein 70 (Hsc70). Like Hsp70, Hsc70 has been shown to bind NS5A and impact infection; however, a direct interaction has not yet been demonstrated, nor have the domains important for complex formation been elucidated. A better understanding of NS5A-driven translation and a delineation of the potential associations formed to initiate that translation may help to identify novel therapeutic targets for HCV.

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Name: Eva Morozko
Home University: Seton Hall University
Major: Biochemistry
Faculty Mentor: Dr. Catherine F. Clarke

Pictured: graduate student Chris Allen, Eva Morozko, and Dr. Catherine F. Clarke

Eva Morozko is a Clare Booth Luce Scholar and will be a senior in the department of chemistry and biochemistry at Seton Hall University, New Jersey. There, she works under the guidance of Dr. James E. Hanson conducting research in organic chemistry. Her current project is in synthesizing meso-Tetrapyridylporphyrin derivatives for DNA quadruplex binding. At UCLA, she is working with Dr. Catherine F. Clarke in the field of biochemistry. Their goal is to further characterize the biosynthetic protein complex responsible for coenzyme Q production in yeast.

Coenzyme Q (Q) is an essential component of electron transport that drives ATP synthesis in eukaryotic respiration. Identified genes coding for the required polypeptides in Q biosynthesis in Saccharomyces cerevisiae (yeast) have been designated as COQ1 through COQ9. At least six of the nine Coq polypeptides required for Q biosynthesis are associated with one or more protein complexes, including Coq3p, Coq4p, Coq5p, Coq6p, Coq7p, and Coq9p. Coq3p first provided evidence of a complex due to co-precipitation of Coq4p. And while a complex containing Coq9p co-precipitated Coq4p, Coq5p, Coq6p and Coq7p, evidence connecting this complex to that of Coq3p is still elusive. It is hypothesized that Coq3p interacts with this larger complex. Eva will attempt to utilize a dual tagging system to more accurately characterize these complexes. Understanding the Q biosynthetic pathway opens numerous opportunities due to the similarities of Q biosynthesis in humans and yeast, which may eventually lead to discoveries regarding Q related disorders.

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Name: Takahiro Ohara
Home University: University of California, Los Angeles
Major: Molecular, Cell, and Developmental Biology
Faculty: Dr. Xian-Jie Yang

Takahiro is a fourth year student at UCLA majoring in Molecular, Cell, and Developmental Biology and minoring in Biomedical Research. Under the guidance of Dr. Xian-Jie Yang at the Jules Stein Eye Institute, he is studying the development of the mammalian retina using genetic tools. After undergraduate education, he plans to pursue an MD/PhD dual degree.

The hedgehog (Hh) family of ligands has been shown to play important roles during the embryonic stages of mouse retinal development. Previously, our lab has shown that Hh signals regulate retinal progenitor cells by promoting their cell cycle progression and influencing their neuronal fate specification. While their importance in prenatal mammalian retinogenesis has been acknowledged, Hh function in the development of late-born retinal cell types during the postnatal stages of mouse retinal development is not well understood. In particular, Takahiro is investigating the role of Hh signaling in the differentiation and maintenance of photoreceptor cells using loss of function analyses. Photoreceptor cells are specialized neurons in the retina that process light, and many retinal degenerative diseases result in the death of these cells. With promising clinical significance, this study will be the first to document the role of Hh signaling in the postnatal mammalian retina in vivo.

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Name: Katrina Owens
Home University: Indiana University of Pennsylvania
Major: Biochemistry
Faculty Mentor: Dr. Marie-Françoise Chesselet

There are many diseases linked to the presynaptic protein alpha synuclein, as a group they are called synucleinopathies. Synucleinopathies include the second most common neurodegenerative disease, which is Parkinson's disease (PD). There are two types of Parkinson's familial and sporadic. It is known that whole gene duplication or triplication of the alpha synuclein gene can cause familial PD. With this link between PD and alpha synuclein, mice that overexpress human alpha-synuclein under the Thy-1 promoter are used in PD research. These mice are often used because they display some of the non-motor and motor dysfunctions of the disease. One recent discovery in the human brain of PD patients is the detection of Lewy bodies and Lewy neurites in the dorsal vagus nucleus before the detection in substantia nigra. These aggregations in the dorsal vagus nucleus are positively stained for alpha synuclein and are linked to cardiac dysfunction in PD patients. In previous research in Dr. Chesselet's lab, it has been shown that the mice that overexpress alpha synuclein have cardiac dysfunction. This summer I will be looking at the expression of alpha synuclein in the vagus nucleus of both wildtype and the mice that have overexpression of alpha synuclein at 1, 5, and 22 months. It is important to understand how close the alpha-synuclein model and PD progression are to each other.

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Name: Aanand Patel
Home University: University of California, Los Angeles
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Joan Valentine

Pictured: Dr. Herman Lelie, Aanand Patel, and Dr. Joan Valentine

Aanand Patel is a third year student at UCLA majoring in Molecular, Cell, and Developmental Biology and minoring in Biomedical Research. He has been working with Dr. Herman Lelie in Dr. Joan Valentine's lab in the biochemistry department for the past year. Aanand studies non-native post-translational modifications to copper/zinc superoxide dismutase (SOD1) in a mouse model.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disease characterized by motor neuron death. Mutations to SOD1, an antioxidant enzyme which catalyzes the dismutation of superoxide radicals, account for approximately 20% of familial ALS cases. Evidence has shown that SOD1 mutants acquire toxicity from an unknown gain-of-function.

ALS patients show increased levels of oxidative stress, and oxidized SOD1 has been associated with Alzheimer's and Parkinson's diseases. Oxidation of wild-type SOD1 with hydrogen peroxide in vitro introduces several oxidative modifications, and these oxidized species of SOD1 adopt aberrant conformations and acquire neurotoxicity in a similar manner to ALS-SOD1. Oxidized SOD1 can also act as an intermediate in covalent cross-linking and aggregation of SOD1. However, oxidative modifications occurring to SOD1 in vivo have not been well characterized. For his current project, Aanand is quantifying the propensities of SOD1 mutants toward oxidation and covalent cross-linking as well as characterizing these non-native modifications to SOD1 in a mouse model.

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Name: Erik Reinertsen
Home University: University of California, Los Angeles
Major: Bioengineering
Faculty Mentor: Dr. Benjamin Wu

The Wu lab utilizes engineering approaches to regenerate lost tissue by designing biomimetic materials and studying mechanisms of cell-microenvironment interactions. Under the guidance of Dr. Benjamin Wu, Erik is investigating how cell distribution affects oxygen availability and viability of cells seeded in thick scaffolds, with the aim of enhancing the viability of engineered cartilage or bone.

Cells cultured in thick scaffolds proliferate sub-optimally due to limited access to oxygen. Bioreactors have been used to convect oxygen and nutrients, but this approach is limited to in vitro applications. Another solution is to enhance angiogenesis with growth factors. However, growth factors are expensive, and release kinetics must be controlled to obtain a desired biological effect. Increasing scaffold porosity and adding channels improves cell viability, but heterogeneous cell growth still occurs when large scaffolds are cultured without convective flow. There is a need for a way to maintain scaffold core cell viability in vivo until angiogenesis occurs.

The Wu lab hypothesizes that core cell viability in a scaffold could be improved by enhancing oxygen availability via seeding cells with increasing cell population density towards the scaffold periphery. Erik will be mathematically modeling the diffusion-consumption of oxygen, as well as cell growth, to guide cell density and distribution for subsequent in vitro experiments. Polymer scaffolds will be fabricated and seeded with pre-osteoblasts to assess cell viability and oxygen tension as a function of seeding density and distribution. Erik will also investigate tracking gold nanoparticle-labeled cells in space and time using microcomputed tomography.

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Name: Christine Ryan
Home University: University of California, Los Angeles
Major: Molecular, Cell, and Developmental Biology
Faculty Mentor: Dr. Donald Kohn

Pictured: Dr. Donald Kohn, Christine Ryan, and Dr. Satiro De Oliveira

Christine Ryan is a fourth-year UCLA student majoring in Molecular Biology and completing a Public Health minor. She has been conducting immunotherapy research in Dr. Donald Kohn's laboratory for the past year under the guidance of Dr. Satiro De Oliveira. Her project involves genetic modification of hematopoietic stem cells to express a chimeric antigen receptor that will enable immune cells to specifically target CD19, a surface molecule that is present in more then 95 percent of leukemias and lymphomas.

A chimeric antigen receptor (CAR) is an engineered fusion protein that combines the specificity of an antibody with the cytotoxic capability of a T cell receptor; a T cell genetically modified to express a CAR is capable of both antigen-specific recognition and directed destruction of target cells, such as tumor cells. While mature T cells can be engineered to express CARs and effectively target tumors in vivo, inadequate persistence of these engineered cells limits clinical success of CAR-mediated therapy. Christine's project investigates genetic modification of hematopoietic stem/progenitor cells (HSPCs) to express a CAR molecule as a novel approach to addressing this limitation. Because HSPCs are able to differentiate into every type of mature blood cell and are also self-renewing, they could potentially serve as a permanent source of CAR-modified cells. Christine's project additionally investigates the inclusion of specific costimulatory domains in the CAR molecule. Determining which CAR structure most effectively directs specific targeting of lekuemic cells is critical to development of a CAR-mediated treatment method for leukemia.

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Name: Sandra Sanchez
Home University: California State University Northridge
Major: Michrobiology
Faculty Mentor: Dr. Beth Lazazzera

Pictured: Dr. Sharon Hoover, Dr. Beth Lazazzera, and Sandra Sanchez

Sandra is a senior at California State University Northridge in the Microbiology department. Under Dr. Michael Summers, she studies how transcription regulates and controls cell differentiation in the cyanobacterium Nostoc punctiforme. Her career objective is to obtain a PhD in microbiology; she loves research and also looks forward to teaching. This summer Sandra is testing a new quorum sensing mechanism for Streptococcus pneumoniae under the mentorship of Dr. Beth Lazazzera and postdoctoral scholar Dr. Sharon Hoover in the MIMG Department.

Quorum sensing is a process that bacterial cells use to communicate and monitor cell density. This process is mediated by secreted signaling molecules that, when they reach a concentration threshold, cause a change in expression of quorum-sensing genes. Bacillus species utilize a unique class of oligopeptides, the Phr peptides, for quorum sensing. Recent bioinformatic analyses have identified putative Phr peptides genes in other bacteria including S. pneumoniae. The goal of Sandra's project is to determine whether S. pneumoniae produces Phr peptides for quorum sensing. The putative Phr gene encodes a precursor protein that is predicted to be secreted and then processed extracellularly to its mature form. The goal of the proposal is to determine which part of the Phr precursor becomes the mature Phr signaling peptide. Sandra will create in-frame deletions in the phr gene to determine which portion of the gene encodes the mature signaling peptide. These studies will contribute to demonstrating that Phr peptides are produced by bacteria other that Bacillus species and developing tools to study the physiological role of Phr peptides in S. pneumoniae.

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Name: Cindy Schmelkin
Home University: Hofstra University
Major: Biochemistry
Faculty Mentor: Dr. Kathleen Kelly

Pictured: Dr. Cheryl Champion, Cindy Schmelkin, and Dr. Kathleen Kelly

Cindy Schmelkin is a rising third year Biochemistry student at Hofstra University in New York. There, she works in the lab of Dr. Nanette Wachter studying the kinetics of the aldol reaction of benzaldehyde with 2'-hydroxyacetophenone (organic compounds) using NMR spectroscopy. As a 2011 Amgen Scholar, Cindy works in the lab of Dr. Kathleen Kelly in the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA.

Dr. Kelly's lab aims to develop a protective vaccine against mucosal tissue infection and resulting pathology by using Chlamydia as a model system. One adjuvant that has proven effective in providing mucosal immunity is the vault protein, a hollow organelle. When packaged with PmpG-1 or MOMP (chlamydial membrane proteins) and introduced into mice, vaults have been shown to offer protection upon challenge with murine Chlamydia.

PmpG-1 is the smaller of the two aforementioned proteins, and has therefore displayed greater efficiency in packaging. Additionally, mice vaccinated with the PmpG-1 vaults displayed faster bacterial clearance. Cindy's project this summer is to determine the most efficient amount of PmpG-1 to package into vault proteins for optimal vaccine delivery. This involves fusing PmpG-1 with the vault interaction domain (INT) and cloning the pmpG-1-INT fragment in frame with a 6-histidine tag. The 6-his tag will facilitate purification, at which point various amounts of PmpG-1-INT-his can be packaged into vaults and the most efficient amount determined. Ideally, Cindy's project will be able to improve upon previous vault formulations and aid in future vaccine studies.

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Name: Joseph Vella
Home University: Rutgers University
Major: Chemical & Biochemical Engineering
Faculty Mentor: Dr. Ken Houk

Joseph is a rising senior at Rutgers University with a major in Chemical & Biochemical Engineering and a minor in Mathematics. At Rutgers, he does research under Professor Yee Chiew in the Department of Chemical and Biochemical Engineering. His research there focuses on studying different thermodynamic models for predicting solubility of pharmaceutical compounds in different organic solvents. This is done computationally, primarily using MATLAB software. After his undergraduate career, Joseph plans to attend graduate school, and continue research in a topic related to chemistry and chemical engineering. Potential areas of interest include thermodynamics, molecular computation, drug delivery, and tissue engineering.

This summer Joseph is working in the Department of Chemistry and Biochemistry at UCLA, under Dr. Ken Houk and graduate student, Ashay Patel. He will be doing computational work in order to explore the origins of diastereoselectivity in different chemical systems. The specific type of reactions being examined are 6p-electron ring closures. Specifically, Joseph will be examining the ring closure of 2-halo-amidotriene systems and 1-azatriene systems. Quantum mechanical computations will be performed using the Gaussian 09 software using density functional theory. These computations will allow the transition states of these reactions to be examined. From the transition state calculations, the diastereoselectivity of the products can be explained. Ultimately these reactions will yield guidelines on how to control stereoselectivities and obtain higher yields of certain diastereomers. These guidelines can then be generalized to related reactions.

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Name: Christopher Wei
Home University: University of California, San Diego
Major: Bioengineering (Biotechnology)
Faculty Mentor: Dr. Hong Wu

At UCSD, Christopher works in Dr. Kun Zhang's integrative genomics lab, developing novel means to target single cell genomes through whole genome amplification and next-generation sequencing. At UCLA, Christopher is working in Dr. Hong Wu's lab under the guidance of Dr. Suzanne Schubbert investigating molecular and cellular effects of VX-680 on PTEN-null leukemia cells.

They have generated a murine T-lymphoblastic leukemia (T-ALL) model by deleting the tumor suppressor gene, PTEN, in fetal mice haematopoietic stem cells (HSCs). Deletion and mutation of PTEN leads to myeloproliferative disorder and eventually T-ALL. Two subsequent mutations are required for the progression to T-ALL in the murine model: ß-catenin activation and t(14:15) Tcra/d-c-myc translocation. The t(14:15) Tcra/d-c-myc translocation causes over-expression of the transcription factor c-myc, which in turn up-regulates Aurora-A kinase (Aurka) and Aurora-B kinase (Aurkb). Both are crucial enzymes for progression through cell cycle and division by regulating chromosome segregation.

Inactivation of Aurkb with the inhibitor, VX-680, leads to polyploidy as DNA synthesis continues without the cell's ability to divide through cytokenesis. The cell consequently recognizes the error and undergoes programmed cell death; consequently halting T-ALL development. Other drugs such as Rapamycin also lead to the cessation of T-ALL initiation and development, but resistant leukemia stem cells (LSCs) survive and pose a threat for continued proliferation of T-ALL. The goal is consequently to determine if VX-680 eradicates not only PTEN-null leukemia blasts but also treatment-resistant LSCs.

Christopher would like to thank Amgen and Wu Lab for the research opportunity.

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Name: Ahuva Weltman
Home University : University of California, Los Angeles
Major: Bioengineering
Faculty Mentor: Dr. Warren Grundfest

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, ongoing research involves using laser-generated shockwaves for the treatment of infected wounds. This project aims to develop a compact, handheld laser-generated shockwave system that fragments bacterial biofilms on wounds while leaving host tissue intact.

This summer, Ahuva will contribute 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. These differences are the basis for FLIM images which map lifetime measurements to a color scale. 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.

The majority of FLIM methods for imaging tissue use laser-generated pulses and exact lifetime measurements to create color maps of cancerous and healthy tissue. LED's, however, are preferable to lasers due to their increased uniformity, low cost, and ability to illuminate large surface areas. Present experiments aim to explore and refine FLIM techniques by using LED's for illumination and comparative lifetime decay times—instead of exact lifetime values that require mathematical deconvolution—for the creation of a tumor imaging system.

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Name: Jamie Yao
Home University : University of California, Los Angeles
Major: Microbiology, Immunonology, & Molecular Genetics
Faculty Mentor: Dr. Aldons Jake Lusis

Pictured: Dr. Brian Parks, Jamie Yao, and Dr. Aldons J. Lusis

Jamie Yao is a fourth-year Microbiology, Immunology, and Molecular Genetics student at UCLA. Under the guidance of Dr. Brian Parks and Dr. Aldons J. Lusis, she is studying LPCAT3, an acyltransferase, and investigating its potential role in inflammation and cholesterol metabolism.

Oxidized phospholipids are pro-inflammatory lipids that promote diverse molecular changes and are important in the development of atherosclerosis. A recent genome-wide association study using human aortic endothelial cells (HAECs) by the Lusis Lab has identified LPCAT3 as a candidate gene for regulating HAEC responses to oxidized phospholipids. Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an enzyme important in mediating the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine, a mechanism of membrane homeostasis. Specifically, LPCAT3 has preferential substrates to add an acyl group to LPC with polyunsaturated fatty acids (PUFAs). PUFAs such as arachidonic acid can serve as precursors to eicosanoids, which have potent inflammatory properties in several cell types. We hypothesize that LPCAT3 regulates oxidized lipid responses by limiting inflammatory eicosanoid production in HAECs by regulating arachidonic acid bioavailability. Elucidation of the role of LPCAT3 in regulating responses to oxidized phospholipids will contribute to our understanding of lipid-induced inflammation, important for atherosclerotic progression.

Jamie is very grateful to the members of the Lusis Lab for their support and teachings. She would also like to thank the Amgen Foundation and the URC-CARE staff for this exciting opportunity.

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