2009 UCLA Amgen Scholars Program

Student Profiles

Mr. Michael Adam

Mr. Christoper Arakawa

Ms. Dorsa Beroukhim

Mr. Andrew Chiu

Ms. Heather Derry

Mr. Bryan Goldsmith

Ms. Jessica Jimenez

Mr. Yong Hoon Kim

Ms. Kathryn Krueger

Ms. Jane Kuon

Mr. Byron Kwan

Ms. Holly Lauridsen

Mr. Eric Lemmon

Ms. Shirley Liu

Ms. Van Mai

Ms. Christie-Lynn Mortales

Ms. Cynthia Neben

Ms. Caitlin Nichols

Mr. Ryan Ponec

Ms. Dianne Pulido

Mr. Jonathan Reuter

Mr. Joseph Rohr

Mr. Tuan Tran

Ms. Allison Wong

Ms. Lacey Wright

Name: Michael Adam
Home University: Brigham Young University
Class: Senior
Major: Biology
Faculty Mentor: Dr. Manuel Penichet

Michael Adam is a fourth year senior majoring in Biology at Brigham Young University. Under the mentorship of Dr. Laura Bridgewater, he has been researching the function of the novel protein nBMP2. At UCLA, he has been working under Dr. Manuel Penichet researching an anti-cancer fusion protein.

Using tumor specific antibodies as a therapy measure against cancer has been shown to be highly effective. Michael’s current research deals with a previously engineered antibody specific to the transferrin receptor (TfR). The transferrin receptor mediates iron uptake, and is expected to be another effective tumor-specific antigen because of the immense need for iron in rapidly multiplying cells such as cancer cells. The antibody engineered by the Penichet Lab includes an avidin protein genetically fused to the carboxy end of the heavy chain. The avidin was fused with the intent of attaching various biotinylated cytotoxic substances to the fusion protein, but has been shown to have an inherent cytotoxic effect. This effect is thought to be a result of cross-linking because of the tetravalent structure of avidin. Michael’s goals for the summer will be to determine the effector functions of the fusion protein relative to the parent antibody without the avidin attached and evaluate the synergism of the fusion protein with the potential therapeutic drug HXR9.

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Name: Christopher Arakawa
Home University: UCLA
Class: Junior
Major: Bioengineering
Faculty Mentor: Dr. Benjamin Wu

Picture of: Dr. Benjamin Wu, Christopher Arakawa, Eric Tsang, Dr. Patricia Zuk

With the help of graduate student Eric Tsang, under the direction of both Dr. Benjamin Wu, and Dr. Patricia Zuk, Christopher is examining the effects of biomimetic apatite on the osteogenic capabilities of human adipose derived stem cells (hASC). By altering the cellular microenvironment he hopes to establish a localized means of inducing osteogenesis.

The Wu lab has previously shown that biomimetic accelerated apatite coating promotes osteogenesis in mouse calvaria MC3T3 cells and adult mouse adipose derived stromal cells and has shown that the local ionic microenvironment, namely calcium and phosphate concentrations, are critical determinants of cell survival, differentiation, or death. However, apatite effects on clinically relevant cells, such as hASC’s are unknown. Although hASC’s proliferate and differentiate less frequently than their rodent counterparts, hASC’s possess similar integrin receptors, ion transporters, and ion channels. Christopher is currently investigating the importance of calcium and phosphate release of apatite on hASC and MC3T3 proliferation and viability. He will attempt to determine the ion release into solution as apatite degrades and the response of both MC3T3 cells and hASC’s. In further studies he will also examine cellular viability after addition of inorganic calcium and phosphate, and then attempt to rescue cell viability with use of calcium blockers and phosphate inhibitors. Studies will serve as a precursor to better understand the effects of biomimetic apatite on human cell lines, possibly leading to an improved and more effective bone regeneration technique.

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Name: Dorsa Beroukhim
Home University: UCLA
Class: Senior
Major: Neuroscience
Faculty Mentor: Dr. Stephanie White

Dorsa Beroukhim is a fourth year student majoring in Neuroscience. She works with Dr. White in the department of Physiological Sciences and is currently researching the expression of CASPR2, identified as an autism susceptibility gene, in the zebra finch brain during development.

The underlying cause of Autism Spectrum Disorder (ASD), characterized by social and behavioral difficulties often with language impairments afflicting more than 500,000 children in the United States, is largely unknown. Before we can fully understand the neural basis of this disorder, a deeper understanding of how the brain learns and produces language is necessary. The White lab investigates the genetic and neural correlates of song learning by targeting brain nuclei dedicated to song learning and production behavior.  

CASPR2 colocalizes with potassium channels at the juxtaparanodes of myelinated axons. (Poliak et al., 2003).  It has been observed that in CASPR2 knock down mice, potassium channels were mislocalized, suggesting that CASPR2 is important in clustering the potassium channels to the juxtaparanodal region. Disruptions to this process may lead to altered neural activity, which may explain the behavioral and language changes observed in autistic children with the mutation. 

The focus of Dorsa's project is to analyze CASPR2 expression and its role at critical time points in song learning development in zebra finch.  By making use of immunohistochemistry and optical imaging techniques, she will be able to characterize Caspr2 expression in relation to song learning and speech, which will further our understanding of the genetic basis of language, and thus autism. 

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Name: Andrew Chiu
Home University: UCLA
Class: Senior
Major: Biochemistry
Faculty Mentor: Dr. Christopher Colwell

 

Andrew Chiu is a third-year Biochemistry major at UCLA. Over the past year, he has been conducting research under the guidance of Dr. Christopher S. Colwell in the Department of Psychiatry and Biobehavioral Sciences. The main goal of the Colwell lab is to understand the molecular, cellular, and systems-level mechanisms that underlie the circadian system in mammals. Andrew has previously investigated the intracellular mechanism by which female sex hormones can alter circadian rhythms during periods of hormonal change. Currently, Andrew is investigating how the absence of certain peptides affects the expression of the genes responsible for generating and maintaining circadian rhythms in mammals.

Recent evidence has suggested that the vasoactive intestinal peptide (VIP) is crucial to the successful generation of circadian rhythms in mammals. Although there is much evidence supporting the crucial role that VIP plays in successful generation of a circadian rhythm, the mechanisms by which VIP works are not yet known. Since circadian rhythms are generated by molecular oscillation, it is of particular interest to determine how VIP affects expression of these circadian clock genes. Under the guidance of the Colwell lab, Andrew will examine the rhythm expression of the Per2 clock gene throughout different phases of the circadian rhythm and determine the impact of the loss of VIP on these rhythms. Andrew’s research will help improve the understanding of how the circadian molecular oscillator functions in mammals.

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Name: Heather Derry
Home University: Ohio Wesleyan University
Class: Senior
Major: Neuroscience, Psychology
Faculty Mentor: Dr. David Hovda

Picture of: Heather Derry, Dr. Mayumi Prins, Dr. David Hovda

As a rising senior Neuroscience and Psychology major at Ohio Wesleyan University, Heather has had the opportunity to complete several summer research programs. After assisting in clinical research at Children’s Hospital of Pittsburgh and behavioral analysis at West Virginia University, Heather is working in Dr. David Hovda’s lab with the Amgen Scholars program. She is working closely with Dr. Mayumi Prins of the Department of Neurosurgery to evaluate a model of mild repeat traumatic brain injury (RTBI).

The subtle deficits of mild TBI may worsen with subsequent head injury to produce more substantial damage, posing a significant problem for groups such as children and athletes who are prone to these injuries. Currently, the Hovda lab is examining a new model of mild RTBI in juvenile rats. Heather uses immunohistochemistry to evaluate the axonal damage associated with RTBI by visualizing antibodies to MBP, GFAP, NF200, and ß-APP. She also examines post-injury behavior through motor, exploration, and object recognition tasks. Another aspect of the present study is evaluating the usefulness of a ketogenic diet in protecting against subsequent injury. Heather hopes to observe appropriate anatomical and behavioral deficits in RTBI rats to validate the model, while comparing these deficits to those of ketogenic rats.

Heather is grateful for this exciting research experience, and would like to thank the Amgen Foundation and the Hovda lab for making this possible

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Name: Bryan Goldsmith
Home University : University of California, Riverside
Class: Senior
Major: Chemical Engineering
Faculty Mentor: Dr. Miguel Garcia-Garibay

Picture of: Matthew Gard, Bryan Goldsmith, Dr. Miguel Garcia-Garibay

Bryan Goldsmith is a 4th year undergraduate majoring in Chemical Engineering at the University of California, Riverside. For over a year, Bryan has been working in Professor Nosang Myung’s Nano-Electrochemical Systems Laboratory synthesizing and characterizing nanowires for possible spintronic and MRAM applications. More specifically, Bryan is fabricating multilayered Permalloy/Cu nanowires by template electrodepostition and creating single nanowire devices on silicon wafers using an electrical alignment technique. Besides research, Bryan will be serving his senior year as Vice-President of Tau Beta Pi, the engineering honors society, along with Treasurer of the American Institute of Chemical Engineering at his home school. Bryan is currently applying to PhD programs and aspires to improve technology through research collaboration along with improving higher education through teaching.

As an Amgen Scholar, Bryan has been working in Dr. Miguel Garcia-Garibay’s laboratory investigating a novel nanopatterning technique. The Garcia Group has proposed a nanopatterning technique using Quantum dot (Qdot) photocatalysis, which may be viable to obtain chemically tailored patterns on an azide-terminated self-assembled monolayer (SAM) by adsorbing Qdot photocatalysts followed by photocatalytic reduction and chemical derivatization. Furthermore, since the surface reaction is Qdot initiated, nanopatterns could potentially be reduced to the size of the Qdot itself, thus providing a route to manufacture surface patterns down to sizes one order of magnitude smaller than nanopatterns formed by conventional techniques. Due to the issue that current azide-terminated SAM synthesis requires up to 7 days time, Bryan’s focus aims to reduce the time required for SAM preparation, which will ultimately increase the efficiency and likely improve the quality of the SAM. Furthermore, from an engineering viewpoint, fewer steps could make the SAM synthesis cheaper and easier for mass production.

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Name: Jessica Jimenez
Home University: UCLA
Class: Junior
Major: Neuroscience
Faculty Mentor: Dr. Carlos Portera-Cailliau

Jessica is a third year neuroscience major, and began working in the laboratory of Dr. Carlos Portera-Cailliau in fall of 2008. The laboratory currently studies the mechanisms by which cortical circuits are assembled in the brain during development. The project Jessica is currently involved in focuses on Cajal-Retzius (CR) neurons, which are known to play a crucial role in neuronal migration through the secretion of reelin. In mice, after cortical layers are properly assembled, CR neurons gradually disappear for reasons that are still not clear to date. Still, a fraction of these neurons remain in Layer 1 into adulthood and continue to extend axons. Therefore, some CR neurons may have other functions in brain development, perhaps playing a role in the structural maturation of pyramidal neurons and their integration into functional cortical circuits. To examine the fate of CR neurons during postnatal mouse development, a transgenic Ebf2 mouse line that expresses the green fluorescent protein (GFP) only in CR neurons can be used. Utilizing two-photon imaging and electrophysiological techniques, Jessica works to begin characterizing surviving CR neuron morphological and electrophysiological properties. If surviving CR neurons do in fact have other functions in the development of the cortical circuit, a comparison between these characteristics at early and adult time points will provide insight needed to begin making inferences about those functions.

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Name: Yong Hoon Kim
Home University: UCLA
Class: Senior
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. Ren Sun

Picture of: Dr Ting Ting Wu, Yong Hoon Kim, Dr. Ren Sun

Yong-Hoon Kim is a 4 th year UCLA student majoring in Molecular, Cell, and Developmental Biology with a minor in Society and Genetics. He joined Dr. Ren Sun’s lab in the Molecular and Medical Pharmacology in the fall of 2007 and has been working with Dr. Ting-Ting Wu and Dr. Seungmin Hwang in developing a novel gamma-herpesviral vector.

The gamma -herpeviruses family includes several pathogenic human viruses such as Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), which cause mononucleosis and primary effusion lymphoma (PEL), respectively. Unlike EBV and KSHV, MHV-68 infects cell lines of various mammalian origins and also efficiently undergoes de novo lytic infection , thus serving as a unique in vivo and in vitro model of the gammaherpesvirus family. During the latent phase of its life cycle, MHV-68 persists as an episome mainly in the memory B cell. Previous studies have shown that the latency-associated nuclear antigen (LANA) encoded by ORF73 plays crucial roles in maintaining latency. As an Amgen Scholar, Yong-Hoon plans to create a recombinant virus which co-expresses LANA and a non-immunogenic cell-surface marker, which will allow for the detection of latently infected cells in vivo. This novel detection method will enable the purification and accurate molecular analyses of latently infected cells

Yong-Hoon would like to thank all the members of the Sun Lab for their support and encouragement, and the Amgen Foundation for the summer research opportunity.

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Name: Kathryn Krueger
Home University: Mount Holyoke College
Class: Junior
Major: Biochemistry
Faculty Mentor: Dr. Stephen Smale

Kathryn Krueger is working in the Smale lab at UCLA. She is studying acquired oncogenic mutations in lymphomas of Ikaros zinc finger four deficient mice. Her work will shed light on the mechanisms that underlie lymphoma growth and development in acute lymphoblastic leukemia. A third year student at Mount Holyoke College, Kathryn has previously studied the physiology and immunology of the rat placenta in Sarah Bacon?s lab on her home campus.

Ikaros, a zinc finger transcription factor, is key to the healthy development of hematopoetic stem cells into mature, differentiated lymphocytes. Mutations in the gene that codes for Ikaros, IKZF1, have been found in 28 percent of acute lymphoblastic leukemia sufferers.
IKZF1 is classified as a tumor suppressor gene. Three different types of Ikaros mutant mouse strains develop thymic lymphoma, though the underlying molecular mechanisms are not yet fully understood.

Concomitant mutations in tumor suppressor genes and proto-oncogenes greatly increase frequency of tumor development. The receptor and proto-oncogene Notch1, plays an important role in lymphocyte differentiation. Upon activation, Notch1 is cleaved from the cell surface to serve as a transcription factor within the nucleus. Mutant forms of Notch1 have been associated with thymic lymphoma.

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Name: Jane Kuon
Home University: UCLA
Class: Senior
Major: Microbiology, Immunology and Molecular Genetics
Faculty Mentor: Dr. Geraldine Weinmaster

Jane Kuon is a 4th year student at UCLA, majoring in Microbiology, Immunology, and Molecular Genetics. In Dr. Gerry Weinmaster’s lab, she is i nvestigating the r equirement for e ndocytic a daptors in D elta-expressing cells to internalize bound N otch receptors.

The Notch signaling system is a highly conserved system, responsible for cell-cell communication. This cell-cell communication occurs between two types of cells: one cell with a transmembrane DSL (Delta/Serrate/Lag-2) ligand, another cell with the transmembrane receptor, Notch.  In mammalian systems, Notch is best known for its roles in cellular differentiation where it can inhibit differentiation in some cells and promote differentiation in others.  Furthermore, growing evidence from the stem cell field suggest that Notch signaling is required for stem cell maintenance. Previous data from the Weinmaster Lab suggests that the Delta expressing cell may be responsible for generating a mechanical force, which exposes the ADAM cleavage site for ADAM activity. Jane will investigate what components of endocytosis and what characteristics of the Delta ligand are responsible for generating this mechanical force within the Delta cells. She will use optical tweezers to measure the force generated by various Delta-expressing cell-lines.

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Name: Byron Kwan
Home University: UCLA
Class: Senior
Major: Bioengineering
Faculty Mentor: Dr. Daniel Kamei

Byron Kwan is a Bioengineering major entering his fourth year of study at the University of California, Los Angeles. He is an Amgen Scholar continuing research in the laboratory of Dr. Daniel T. Kamei in the Department of Bioengineering. Byron is investigating the use of a genetically engineered transferrin to enhance delivery of cytotoxins to glioma and lung cancer cells.

The human iron transport protein, transferrin, has been utilized in the past by several research groups as part of a cancer treatment where transferrin was used as a cancer selective targeting molecule for an attached cytotoxin (transferrin conjugate). Prior investigations in the Kamei laboratory led to the development of mutant transferrins that serve as more effective delivery vehicles. Previously conducted studies demonstrated that the mutant transferrin conjugates are capable of killing HeLa cells (a human cervical cancer cell line) more effectively than the conventional wild-type transferrin conjugates. Byron looks to extend these results to other cancer cell lines; in particular, he is investigating the effects of wild-type and mutant transferrin conjugates on glioma and non-small cell lung cancer cell lines. To do this, he will analyze the cytotoxicity of the transferrin conjugates using the sulforhodamine-B assay, which measures cell viability as a function of total protein content. Byron’s experiments will allow the laboratory to gauge the ability of both the mutant and wild-type transferrin conjugates to apply to different cancers in vitro and also provide insight on possible future in vivo studies.

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Name: Holly Lauridsen
Home University : Brown University
Class: Junior
Major: Biomedical Engineering
Faculty Mentor: Dr. Jaunian Chen

Picture of: PhD student Kevin Mouillesseaux and Holly Lauridsen

Holly Lauridsen is a third year student at Brown University, majoring in biomedical engineering. Holly previously worked in a neurotoxicology lab at Oregon Health and Science University, but has since decided to focus on the cardiovascular system. This summer she is working in UCLA’s Molecular Cell and Developmental Biology (MCDB) department with Dr. Jau-Nian Chen, using a zebrafish model to study vascular development.

The vascular system consists of two distinct types of vessels, arteries and veins. While differences in these two vessels were previously attributed to unique flow environments, more recent research indicates that arteriovenous differentiation is the result of genetic components before circulation begins. Holly studies this differentiation using zebrafish, a popular model in developmental biology, especially in cardiovascular research. Unlike other animal models, zebrafish with extreme vascular defects are able to survive during early development due to the diffusion of oxygen across their skin to maturing tissues. A number of the genetic components involved in zebrafish vessel development, which Holly utilizes in her research, have already been identified. The initial goal of her research involves selecting two genes: one which is expressed in all endothelial cells and a second which is restricted to either the veins or the arteries. These two genes will originally be tested using in situ hybridization for their expression quality and selectivity in the blood vessels. Single and double in situ hybridizations are colorimetric assays, which will aid in the selection of the best genes for a transgenic fish. When this gene pairing has been identified, fluorescent markers will be inserted into the zebrafish genes, so that a new transgenic line where veins and arteries are distinguishable based solely on fluorescent expression will be created. This model will then be used in Holly’s future cardiovascular research to help identify vascular developmental problems.

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Name: Eric Lemmon
Home University: McDaniel College
Class: Senior
Major: Biology, Chemistry and Physics
Faculty Mentor: Dr. Ken Houk

Eric Lemmon is a fourth year student at McDaniel College in Maryland. He has a triple major in biology, chemistry, and physics. He plans to pursue an MD/PhD dual degree following this academic year. This summer he is working in the Houk Group at UCLA under the tutelage of Professor Ken Houk and graduate student Geoff Nosrati. He is working on the computational design of an enzyme to catalyze a Diels-Alder reaction, specifically the one between alpha anomeric glucosyl oxy-butadiene and methacrolein. No natural catalyst exists for Diels-Alder reactions.

The process of enzyme engineering involves the use of computational programs, specifically Gaussian and Rosetta in this circumstance. A theoretical active site, or theozyme, will be devised by calculating the energy of the transition state of the uncatalyzed reaction. Following this, a lysine side-chain mimic will be used to lower the activation energy barrier. The theozyme will then be placed into a protein scaffold and the neighboring side-chains will be mutated in order to produce good packing. Once designed the protein will be expressed in recombinant E. coli and tested for catalytic activity. An effective catalyst could see a potential use in drug synthesis.

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Name: Shirley Liu
Home University: UCLA
Class: Junior
Major: Biology
Faculty: Dr. Irvin Chen

Shirley has been working in Dr. Irvin Chen’s laboratory in the department of Microbiology, Immunology, and Molecular Genetics since her freshman year. Her current project involves increasing the efficiency of hematopoietic differentiation from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC).

Hematopoietic lineages of hESC or hiPSC are of major interest for many clinical applications involving cell-based therapeutics. Directed differentiation of hiPSC into hematopoietic progenitor cells is an alternative to conventional sources of cells, which require tissue matching and present the risk of disease transmission. The efficiency of differentiation, however, is very low. This summer, Shirley is inducing differentiation of hESC and hiPSC by co-culture with stromal cells and the formation of embryoid bodies using cytokines, as well as a combination of the two major methods. She will be optimizing this differentiation, testing different experimental conditions. In order to distinguish differentiated cells, she will be using an assay system involving microRNA target vectors linked to fluorescent markers, as undifferentiated hESC and hiPSC differ in expression of specific microRNA. Flow cytometry can be used to analyze fluorescence as well as the presence of CD34 and CD43 markers, both of which are characteristic of hematopoietic lineages. In addition, Shirley will be screening hiPSC for differentiation into myocardiac, neural, hematopoietic, and germ layer (ectoderm, mesoderm, endoderm) lineages, in order to confirm pluripotency.

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Name: Van Mai
Home University: UCLA
Class: Senior
Major: Biochemistry
Faculty Mentor: Dr. Dolores Bozovic

Van is studying the activity of inner ear hair cells in the bullfrog sacculus. In the auditory system of vertebrates, hair cells are the primary sensory cells that utilize an active process to achieve amplification of low-level input. The manifestation of this active process is spontaneous otoacoustic emission (SOAE), the generation of sound from the inner ear. Thus far, the process responsible for SOAE is not known, and the project Van is involved in aspires to undertake this challenge.

In the bullfrog sacculus, hair bundles, stereocilia projecting from the apical surface of hair cells, exhibit oscillation in the absence of external stimulation. When the otolithic membrane, an extracellular matrix overlying the hair bundles, is removed, neighboring hair bundles in the bullfrog sacculus spontaneously oscillate with phase and frequency independent of one another. However, spontaneous oscillation is not observed when the otolithic membrane remains connected to the hair bundles. Van is investigating the hypothesis that if only hair cells in certain regions of the epithelium were to oscillate together and vibrate the overlying membrane, they would give rise to more macroscopic movement, sufficient to explain otoacoustic emission. This hypothesis is tested by coupling several hair bundles in a region with an artificial membrane composed of poly (lactide-co-glycoside) coated with Wheat germ agglutinin, a lectin that binds specifically to sialic acid and N-acetylglucosaminyl residues found on the membrane of hair bundles, and comparing the oscillations of hair bundles before and after they have been coupled together by the artificial membrane.

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Name: Christie-Lynn Mortales
Home University: University of Washington, Seattle
Class: Senior
Major: Biology
Faculty Mentor: Dr. Carrie Miceli

Picture of: Christie-Lynn Mortales, Dr. Carrie Miceli, Oscar Silva

At the UW, Christie currently works in Dr. Brian Iritani’s lab and studies the effect of Myc, an oncoprotein, on B cell development. Her previous project involved investigating Myc’s regulation on immunoglobulin production, with a focus on IgE. Following her post baccalaureate studies, she plans to pursue an MD/PhD in pediatrics and immunology.

An ever-increasing field of research is identifying how the interaction between a T lymphocyte and antigen presenting cell (APC) leads to certain cellular and molecular outcomes and immune responses. This interaction occurs through the association of antigen on an APC’s MHC molecule with a T cell’s TCR. This forms a physical contact site called the immunological synapse – which requires the dynamic reorganization of transmembrane proteins and actin cytoskeleton through the specific localization of actin polymerizing and membrane adhesion proteins – initiating T cell receptor (TCR) signal transduction.

Discs large homolog 1 (Dlgh1), a membrane-associated scaffold protein, mediates TCR signal transduction through the localization of tyrosine kinases, ZAP-70 and Lck. Additionally, Ezrin, a FERM family protein involved in actin cytoskeleton reorganization via membrane-cytoskeleton adhesion, has been shown to associate with Lck and ZAP-70 during T cell activation. Dlgh1 is made up of several binding domains conserved between cell types, one of which is the i3 domain. Furthermore, it is known that FERM family proteins bind to certain domains, such as the i3 domain, of Dlgh1 in other cell types.

The focus of Christie’s work in Dr. Carrie Miceli’s lab (UCLA) will be to determine the requirements for Ezrin association with Dlgh1 in T cells, with a focus on the i3 domain. This study will give insight on the mechanisms that regulate T cell activation, immunological synapse membrane reorganization, and how TCR signaling leads to specific functional outcomes.

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Name: Cynthia Neben
Home University: Chapman University
Class: Senior
Major: Biological Sciences
Faculty Mentor: Dr. Fuyu Tamanoi

In Dr. Jennifer Funk’s lab at Chapman University, Cynthia studies the development of methods that examine inter-specific differences in leaf nitrogen biochemistry to better understand the mechanisms of invasive species success. As a UCLA Amgen Scholar in Dr. Fuyu Tamanoi’s lab in the Microbiology, Immunology, and Molecular Genetics Department, Cynthia examines the effects of geranylgeranyltransferase-I inhibitors (GGTIs) on different cancer cell lines to determine if they are cell line dependent.

G eranylgeranylated proteins are a result of protein prenylation, a post-translational lipid modification of proteins that occurs in the cytosol. G eranylgeranylated proteins are modified by geranylgeranyltransferase-I (GGTase-I). Recent studies have highlighted the biological significance of protein geranylgeranylation, particularly in cancers. The g eranylgeranylated proteins Ral, RhoA, and RhoC have been revealed to play vital roles in tumor progression and metastasis. Cells lacking GGTase-I show proliferation inhibition and accumulation of p21, pointing toward the significance of GGTase-I in cell proliferation and cell cycle progression.

Dr. Tamanoi’s lab, in collaboration with the Department of Chemistry and Biochemistry at UCLA (Dr. Ohyun Kwon’s lab), has synthesized small molecule inhibitors of GGTase-I. One of the modified compounds has been shown to be a more potent inhibitor of GGTase-I activity in pancreatic cancer cell lines when compared to previous inhibitors of GGTase-I (GGTIs). Cynthia investigates whether cancer cell lines respond in the same manner to GGTI treatment by detecting the induced expression levels of p21 and p27. Understanding the effects of inhibitors of protein geranylgeranyltransferase-I on levels of p21 and p27 in cancer cell lines provides a promising approach for developing anticancer drugs.

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Name: Caitlin Nichols
Home University: Brigham Young University
Class: Junior
Major: Molecular Biology
Faculty Mentor: Dr. Yibin Wang

Picture of: Dr. Yibin Wang, Caitlin Nichols, Dr. Asuka Ota

Caitlin has worked in the molecular biology lab of Dr. Laura Bridgewater at Brigham Young University since May 2008. Her research in Dr. Bridgewater’s lab involves studying the role of the unfolded protein response in the pathologies exhibited by mice with the cho, Dmm and sedc collagen mutations, as well as investigating the function of nBMP2, a novel nuclear variant of the secreted growth factor BMP2.

As a UCLA Amgen Scholar in Dr. Yibin Wang’s lab, Caitlin researches the role of the novel endoplasmic reticulum (ER)-localized phosphatase PP2Ce in regulating the unfolded protein response (UPR) during adipogenesis. The UPR occurs when the cellular load of protein production exceeds the ER’s synthesis and folding capacity, causing ER stress. This pathway helps relieve ER stress by decreasing net protein production while increasing the ER’s ability to process unfolded proteins. The IRE1α-XBP1 branch of the UPR pathway helps modulate adipogenesis through regulating expression of an important lipogenic factor, and is triggered when accumulation of unfolded proteins in the ER activates the ER membrane-localized protein IRE1α. This event leads to the translation of the transcription factor XBP1, which upregulates UPR genes. The ER-membrane protein PP2Ce, through its IRE1α-specific phosphatase activity, may help modulate the UPR as a whole during adipogenesis. Since adipogenesis plays an important role in the onset of diseases such as diabetes, hypertension, atherosclerosis, coronary heart disease and obesity, understanding PP2Ce’s regulatory role during this process will help illuminate the development of these conditions and may lead to new options for treatment.

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Name: Ryan Ponec
Home University : UCLA
Class: Senior
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. Luisa Iruela-Arispe

Ryan Ponec is a 4 th year Molecular, Cell, and Developmental Biology major and Biomedical Research minor at UCLA. He works in the lab of Dr. Luisa Iruela-Arispe, studying the emergence of hematopoietic stem cells in a mouse model system. He is a recipient of the UCLA Regents Scholarship and has participated in the American Heart Association Undergraduate Student Research Program and the UCLA Undergraduate Research Fellows Program.

During development, the emergence of hematopoietic stem cells (HSCs) occurs over a period of days in several locations. Intra-embryonic vascular sites, which include the aortic gonado-mesonephric region as well as the vitelline and umbilical arteries, have been characterized as independent sources of HSCs. These cells are derivatives of the endothelium. Using a mouse model system, members of the lab have observed a unique phenomenon in the vitelline artery where HSC aggregates appear to leave the vasculature and enter the surrounding tissues. Using a Cre-lox reporter system to specifically label endothelial cells and their HSC derivatives with a fluorescent marker, Ryan is working on establishing an imaging system where this budding process can be observed in real time. In addition, he will work on characterizing the role of Notch-1 in HSC emergence using an endothelial specific Notch-1 knockout mouse.

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Name: Dianne Pulido
Home University: UCLA
Class: Junior
Major: Bioengineering
Faculty Mentor: Dr. David Krantz

Picture of: Dr. David Krantz, Dianne Pulido, Dr. Hakeem Lawal

Dianne Pulido is a third year Bioengineering student at UCLA. As a first year student, she began her research at the California Nanosystems Institute studying the formation of nanowires from viruses. She then went on to her current work with Dr. David Krantz as part of the Neuropsychiatric Institute, where she has been studying changes to Drosophila vesicular monoamine transporters (dVMAT) in relation to neuropsychiatric illnesses for over a year.

Aminergic signaling pathways in both mammals and Drosophila are dependent on vesicular transporters for the packaging and release of neurotransmitters. In humans, neuropsychiatric disorders such as Parkinson's disease and depression have been connected to impairments in the function of VMAT affecting the levels of dopamine and serotonin present in neurons. By studying mutations to dVMAT-A, the Drosophila homolog of mammalian VMAT-2, it is possible to trace how changes to the transporter induce noticeable behavioral and physiological differences that could offer more insight into the molecular mechanisms involved in amine-regulated synaptic transmission. As one of her first projects, Dianne collaborated in a large drug screen aiming to identify specific drugs that could improve the function of dVMAT-A in the trafficking of amines. The results of the drug screen fed into a current secondary genetic screen, where synaptic proteins will similarly be tested for enhanced dVMAT-A activity. Dianne also concurrently studies synaptic proteins as neuroprotective agents by following the survival of Drosophila lines that are exposed to neurotoxins, where survival could indicate adaptive responses to neurodegenerative conditions.

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Name: Jonathan Reuter
Home University: University of California, San Diego
Class: Senior
Major: Bioengineering
Faculty Mentor: Dr. William Klug

Previously, Jonathan has conducted research in the fields of vascular mechanotransduction and signal transduction as part of the Chien lab at UCSD. In the Cardiac Mechanics Research Group, also at UCSD, he has helped automate finite element mesh generation for cardiac modeling. As an Amgen Scholar at UCLA, Jonathan is working with Dr. William Klug in the Department Mechanical and Aerospace Engineering to develop a finite element model of viral capsid assembly.

From a structural standpoint, viruses are a well understood aspect of biology. A viral capsid consisting of repeating protein subunits serves to encapsulate and protect the infectious genetic material, RNA or DNA depending upon the virus. Most viruses fall into two primary morphologies, helical and icosahedral. Icosahedral viruses are comprised of pentamers and hexamers subunits that come together to form a near-spherical shell. However, the process by which capsids assemble has yet to be elucidated. Utilizing a mathematical free energy model of the capsid system, computational simulations will be run in order to determine energetically favorable patterns of icosahedral viral assembly. Visualization of these results will lead to new insights about geometric growth motifs and interfacial instability. Through parametric studies, Jonathan will investigate the influence of elastic, thermodynamic, and chemical properties of the system on the assembly process. In addition, he will be responsible for implementing changes to the model motivated by biological considerations.

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Name: Joseph Rohr
Home University: Tulane University
Class: Junior
Major: Biological Chemistry, French
Faculty Mentor: Dr. Hanna Mikkola

Joseph Rohr is a junior at Tulane University in New Orleans, Louisiana, studying for a BS in Biological Chemistry and a BA in French. He works in the lab of Dr. YiPing Chen, exploring the mechanisms behind the genesis of the tooth and palate. In Dr. Hanna Mikkola’s lab at UCLA, Joseph is examining the mechanisms of hematopoietic stem cell ( HSC) emergence by comparing normal emergence in the wild-type mouse to the impaired emergence in the Ncx -/- model which has no heartbeat.

It has been recently resolved that HSCs emerge in normal development from hemogenic endothelia, a sub-type of arterial endothelia present in all blood-forming locations in the conceptus. In Ncx mutants, HSC emergence is significantly impaired, although it has been shown that mutant placentas can generate HSCs if cultured ex vivo. It has been shown that the arterial marker Notch1 is downregulated in normal emergent HSCs and that mutant proto-HSCs express excess Notch1. Thus, Joseph’s group hypothesizes that Notch1 needs to be downregulated in order for endothelia to commit to the hematopoietic identity. He will examine factors that may be related to Notch1 overexpression in vivo, including Hif2a, VegF, and nitric oxide, to determine their expression patterns in both mouse models as well as use over- and under-expression experiments to attempt to rescue the hematopoietic phenotype in the mutants. Joseph’s research will shed light on the mechanisms behind HSC emergence and will be a stepping stone on the path to culturing stable populations of undifferentiated HSCs.

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Name: Tuan Tran
Home University: UCLA
Class: Senior
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. April Pyle

Tuan Tran is a fourth year Molecular, Cell and Developmental Biology major and a Biomedical Research minor conducting research under the mentorship of Dr. April Pyle. Upon completing his undergraduate studies, Tuan will pursue a dual MD/PhD degree.

Human embryonic stem cells (hESCs) isolated from the inner cell mass of blastocysts are pluripotent and can continuously self-renew. Recent work has shown that transducing human adult fibroblasts with four key transcription factors can generate induced pluripotent stem cells (iPSCs), which appear to be virtually indistinguishable from their hESC counterparts. Despite these recent advances, there remains great variation in both methodology and efficiency of generating differentiated lineages from either hESCs or hiPSCs. Of particular difficulty has been the development of reliable protocols to efficiently differentiate skeletal muscle lineages. We are currently establishing an alternative protocol for directing differentiation of hESCs and hiPSCs toward muscle lineage. hESCs and hiPSCs have been differentiated into embryoid bodies (EBs) in attempt to identify the optimal time point at which there is maximal enrichment for early stage or progenitor muscle markers. EBs are aggregates of cells that are thought to recapitulate early embryonic development by coaxing the cells to differentiate into all three germ layers. EBs at the time point in which muscle progenitor markers are expressed will be dissociated, expanded, and terminally differentiated in standard culture conditions for promoting muscle cell growth and differentiation. In a multi-faceted approach, experiments are in progress to increase the efficiency of producing muscle progenitor cells by overexpressing MyoD in pluripotent stem cells (PSCs) or skeletal muscle progenitors. Establishment of standard protocols for generation of muscle progenitor cells from PSCs will be used in future experiments for assaying the differentiation potential of Duchenne Muscular Dystrophy (DMD) patient-specific hIPSCs.

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Name: Allison Wong
Home University : UCLA
Class: Junior
Major: Biochemistry
Faculty Mentor: Dr. Paula Diaconescu

Allison Wong is a 3 rd year Biochemistry student at UCLA. Currently, she works in the Chemistry department in the group of Dr. Paula Diaconescu studying organometallic complexes. More specifically, she is interested in the reactivity of group III metal complexes towards aromatic nitrogenous heterocycles, which has implications for the purification of fuels.

Prior studies have found few organometallic catalysts which can cleave the C-N bonds of N-heterocycles. The Diaconescu group (UCLA) has described the ring opening of a substituted imidazole molecule by a scandium alkyl complex supported by a silylated ferrocene ligand, and is currently investigating the ring opening reactions of more chemically robust and industrially significant pyridines. Allison is investigating the reactivity of a lutetium alkyl complex in analogous reactions involving methylimidazole and benzimidazole. By varying the supporting ligand, she influences the reactivity of the metal alkyl complex by steric and electron donating effects. She is interested in developing alternate ferrocene based ligands, and also in the use of ruthenium or osmium as secondary metal centers. These reactions have significance for the industrial breakdown and removal of pyridine rings from bitumen and oil shale, as present catalysts are both expensive and environmentally unsound. The discovery of homogeneous organometallic catalysts which cleave C-N bonds could enable cleaner, greener processes and help elucidate unexplored reactivity of group III metals.

Name: Lacey Wright
Home University : University of Rhode Island
Class: Senior
Major: Biological Sciences
Faculty Mentor: Dr. Linda Baum

As a 2009 Amgen Scholar at UCLA, Lacey will contribute to research in the laboratory of Dr. Linda Baum by investigating the role of endogenous galectin-1 in Nipah-F and Nipah-G mediated syncytia formation.

Nipah virus (NiV) is a newly emerged viral pathogen. In humans, NiV causes mortality rates up to 74% by infecting endothelial cells and causing cell to cell fusion called syncytia formation. This fusion causes endothelial cell damage and necrosis, often leading to severe acute encephalitic syndrome in infected individuals. NiV-F and NiV-G are two envelope glycoproteins that are critical in the formation of NiV-induced syncytia. NiV uses NiV-G to attach to the cell membrane and NiV-F to fuse to host cells. After infection, syncytia formation is attributed to the expression of NiV-F and NiV-G on the host cell membrane, which causes the cell to attach and fuse to other host cells.

The Baum lab has previously shown that galectin-1, an endogenous lectin, inhibits the formation of syncytia in cell infection with NiV. This summer, Lacey will be examining the role of endogenous gal-1 in NiV-F and NiV-G mediated syncytia formation by quantifying the amount of gal-1 produced by resting, activated, and inhibited human umbilical vein endothelial cells on a per-cell level, and measuring the effect of altering galectin-1 expression on syncytia formation.