2008 UCLA Amgen Scholars Program

Student Profiles

Ms. Vicky Braun

Ms. Feng Cao

Mr. Derrick Chu

Ms. Michelle Crespo

Mr. Lorenzo D'Amico

Mr. Steven Gee

Mr. David Goldenberg

Ms. Iris Claire Ha

Mr. Steven He

Ms. Vivian Hecht

Mr. Samuel Israel

Mr. Sattar Khoshkhoo

Mr. Jose Matteo

Ms. Meghan McKeon

Mr. Karan Mehta

Ms. Michelle Riener

Ms. Stacey Shiigi

Ms. Amy Steinmetz

Ms. Tamara Tasoff

Ms. Wendy Tseng

Ms. Jenna Wilson

Mr. William Wong

Ms. Joan Zape

Ms. Shabnam Ziaee

Name: Vicky Braun
Home University: University of Indianapolis
Class: Senior
Major: Cellular and Molecular Biology
Faculty Mentor: Dr. Utpal Banerjee

Under the tutelage of Dr. Mary Ritke at the University of Indianapolis, Vicky is currently investigating the proteins involved in the signal transduction pathways responsible for apoptosis in chick embryo fibroblasts, including caspase 3’s cleavage of PARP1. Vicky’s goal is to establish chicken embryonic fibroblasts as a model cell line. As a UCLA Amgen Scholar in Dr. Uptal Banerjee’s lab in the Cell and Molecular Biology department, Vicky is working on hematopoiesis in Drosophila melanogaster .

The lymph glad is the known hematopoietic organ in Drosophila larvae, but during the final stage of pupation the lymph gland dissociates. Vicky aims to determine if the haematopoietic precursors from the larvae are maintained in the adult and discover where they are located. To accomplish this goal, fluorescently labeled larval lymph glands will be transplanted into the adult Drosophila to detect changes in blood cell count. In linage tracing experiments, genetically labeled cells of the larval lymph gland will be traced to determine where the stem cells are maintained as the organism develops into an adult.

Vicky plans to apply for the Ph.D. program at UCLA and would like to thank Amgen and the Banerjee lab for all of their help and encouragement.

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Name: Feng Cao
Home University: UCLA
Class: Junior
Major: Chemistry
Faculty Mentor: Dr. Richard Kaner

Feng is an incoming fourth year chemistry student at UCLA. She has been working with Dr. Richard B. Kaner’s group in the Department of Chemistry and Biochemistry for about two quarters. She is currently working on semi-conducting organic polymers, materials that possess band gaps and nanostructures. In recent years, there is growing interest on these materials due to their great potential for many technological applications. Polyaniline and polythiophene are types of organic semiconductors that possess morphologies at the nano-scale. Polyaniline can be used as chemical sensors for the purpose of detecting toxic gases, whereas polythiophene nanofibers can be used in solar energy cells due to its high chemical and electrochemical stabilities. Finding an easy way of synthesizing these semi-conducting polymers on the nano-scale will be extremely useful for the industrial applications. In recent studies, polyaniline and polythiophene nanofibers have been successfully synthesized by providing homogeneous nucleation conditions to the radical polymerization. Feng's goal for this summer is to synthesize 3-hexylpolythiophene nanofibers, which can be put into the applications of solar energy cells

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Name: Derrick Chu
Home University: UCLA
Class: Junior
Major:Molecular Cell and Developmental Biology
Minor: Biomedical Research
Faculty Mentor:
Dr. Ren Sun

From left to right: Shaoying Lee, Derrick Chu, Ren Sun

Working with Dr. Ren Sun and graduate student Shaoying Lee of the Molecular and Medical Pharmacology Department, Derrick is investigating late gene regulation in gammaherpesvirus. The family of gammaherpesvirus include human viruses such as Epstein Barr Virus (EBV), responsible for mononucleosis, and Kaposi's Sarcoma-associated herpesvirus (KSHV), responsible for the lesions seen in AIDS patients. Because of the limitations involved with studying EBV and KSHV in vitro, Murine Gammaherpesvirus 68 (MHV-68), a pathogen of rodent species, will be used a model organism of study. To discern the mechanism by which MHV-68 regulates late gene expression, especially in relation to latent replication, he will characterize the role of ORF31, ORF24, and ORF 34 thought to be involved with late gene expression. Previously, a yeast two-hybrid assay of the MHV-68 genome has determined a close interaction between ORF24 and 34 as well as ORF31 and the cellular gene NDP52. The binding of these proteins will be characterized biochemically and the role of these interactions in late gene expression will be analyzed using mutant virus constructs in hopes of determining how MHV-68 late genes are regulated.

 Derrick is currently a third year Molecular Cellular and Developmental Biology major with a minor in Biomedical Research. He intends to pursue a departmental honors thesis in the fall continuing under the guidance of Dr. Sun.

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Name: Michelle Crespo
Home University: UCLA
Class: Junior
Major: Neuorscience
Faculty Mentor: Dr. Carlos Portera-Cailliau

Michelle began conducting research in the laboratory of Dr. Carlos Portera-Cailliau in spring of 2007. The laboratory currently studies how the neocortex is assembled during normal development. The project Michelle is involved in specifically focuses on the period of synapse formation in the neocortex and how it is disrupted in Fragile X syndrome (FXS), the most common inherited form of human mental retardation and autism. The brains of individuals affected with FXS, as well as mutant mice lacking the Fmr1 gene (Fmr1 KO), contain abnormally long and thin dendritic spines that resemble their immature counterparts, dendritic filopodia. Observed differences in length, density, and dynamics of protrusions in Fmr1 KO mice might lead to early synaptic abnormalities since they occur during the first two postnatal weeks. Using acute slices, Michelle is investigating whether the increased spine length seen in Fmr1 KO mice is associated with defective spatial distribution of postsynaptic densities or abnormal synapse number. She utilizes techniques such as in utero electroporation and two-photon imaging of layer 2/3 pyramidal cells to reveal more about the synapse formation and elimination processes in Fmr1 KO mice.

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Name: Lorenzo D'Amico
Home University: UCSD
Class: Senior
Major: Bioengineering: Biotechnology
Faculty Mentor: Dr. Harold Monbouquette

From left to right: Lorenzo D'Amico, Harold Monbouquette, Vanessa Tolosa

In Dr. Gabriel Silva’s lab at the UCSD Jacobs Retina Center, Lorenzo uses functionalized semiconductor quantum dots to track physiological processes in neurons and glia with the goal of elucidating the molecular dynamics of reactive gliosis following central nervous system injury. As a UCLA Amgen Scholar in Dr. Harold Monbouquette’s lab in the Chemical and Biomolecular Engineering Department, Lorenzo is working to develop a microelectode array biosensor capable of detecting multiple analytes in vivo.

Abnormalities in neurotransmitter transmission contribute to a number of neurological and psychiatric disorders. The development of systems for the continuous monitoring of neurotransmitter concentrations in vivo is therefore an important goal in neuroscience. Dr. Monbouquette’s lab has developed an amperometric microelectrode array biosensor to detect L-glutamate transmission in rat brain. The sensing principle entails the use of glutamate oxidase which in the presence of glutamate catalyzes a reduction/oxidation reaction that yields hydrogen peroxide. In this biosensor, the enzyme is immobilized on to the surface of an electrochemical sensor that detects hydrogen peroxide, converting the biological signal to an electric signal. Lorenzo is working to develop an immobilization strategy to spatially control the deposition of enzyme to targeted electrode sites on the biosensor. By limiting the deposition to specified sites, it will be possible to detect multiple analytes with the same implantable sensor. This augmentation will provide neuroscientist with a tool to better understand the biochemical abnormalities that underlie neurological disorders.

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Name: Steven Gee
Home University : California State University of Los Angeles
Class: Senior
Major: Biochemistry
Faculty Mentor: Dr. Michael Levine

 

In Dr. Nickolaisen’s physical chemistry lab at CSULA, Steven has studied alkyl peroxy radical formation and its role in ozone formation. In Dr. Levine’s lab in the department of neuroscience at UCLA, Steven is researching the role of CAG repeat length in Huntington’s disease phenotype.

Huntington’s disease is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG repeat found in exon 1 of the huntingtin gene. Symptoms typically present in midlife and include motor abnormalities manifesting as dance-like movements (chorea), mood disorders and cognitive disturbances. In humans, the number of CAG repeats is inversely proportional to the age of onset. Previous electrophysiologcial experiments in Dr. Levine’s lab have revealed a number of alterations in the striatum of the R6/2 mouse (an HD mouse model), including a progressive decrease in excitatory postsynaptic current (EPSC) frequency and increase in inhibitory postsynaptic current (IPSC) frequency. In addition, a reduced latency to seizures has been observed in the R6/2 mouse. Four lines of R6/2 mice have been obtained carrying 110, 150, 210, and 310 CAG repeats, respectively. Steven will perform whole-cell patch clamp experiments in visually identified, striatal medium-sized spiny neurons to measure basic membrane properties and EPSC and IPSC frequency. In addition, s eizures will be induced in the transgenic mice by intraperitoneal injection of picotoxin. Given the CAG repeat dependency of Huntington’s disease in humans, he predicts that R6/2 mice with higher CAG repeats will be more affected than those with the lower repeats.

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Name: David Goldenberg
Home University: UCLA
Class: Senior
Major: Psychobiology
Faculty Mentor: Dr. Warren Grundfest

David Goldenberg has worked with Dr. Warren Grundfest since Spring 2007 in the Department of Bioengineering, researching hard and soft tissue mimicking materials for the construction of ultrasound phantoms. Ultrasound phantoms are substances that mimic the ultrasonic properties of specific tissues.

Ultrasound imaging has been used to detect density or acoustic impedance changes in tissues. It can be utilized in air- or water-filled organs, at bone/soft tissue interfaces, and with foreign objects in soft tissue. Ultrasound imaging of soft tissues is well established, but the imaging of hard tissue surfaces and abnormalities has not found widespread clinical ap­plication in the United States. Hard tissue phantoms that mimic the acoustic properties of human tissues are required to better understand the interaction of acoustic waves with bones and joints in order to develop and calibrate ultrasound imaging systems. Because several studies have demonstrated accurate soft tissue phantoms, David is developing hard tissue mimicking materials for the characterization of the lab’s novel flexible, conformable ultrasound transducer. After being able to craft phantoms that accurately mimic speed of sound, acoustic impedance, and attenuation of bone, David will design a novel anthropomorphic phantom consisting of fractured hard tissue submerged in soft tissue to simulate a broken bone in vivo.

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Name: Iris Claire Ha
Home University: UCLA
Class: Junior
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. William Lowry

Human induced pluripotent stem (iPS) cells can be generated from adult somatic cells through ectopic expression of the transcription factors Oct4, Sox2, c-Myc, and Klf4. These iPS cells are nearly identical to embryonic stem cells (ESCs) in morphology, gene expression, epigenetic state, as well as pluripotency. While murine iPS cells have been shown to produce viable chimeras and exhibit random X-inactivation upon differentiation, little is known about the quality of human iPS-derived tissue. As a 2008 Amgen Scholar, Iris is working with Dr. Bill Lowry to isolate iPS-derived keratinocytes in order to later characterize and assess the quality of human iPS-derived epithelial tissue.

Isolating human keratinocyte precursors from embyoid bodies is difficult because no reliable keratinocyte-specific extracellular proteins have been identified, and transgenic human cell lines are not available. Previous studies on ESC-derived human keratinocyte precursors have remedied this problem by immunostaining for various keratinocyte differentiation markers. However, this method of isolation requires tissue fixation and results in nonliving cultures. In order to isolate the living iPS-derived keratinocyte precursors needed for this study, Iris and Dr. Lowry are identifying faithful promoter regions for keratinocyte differentiation markers and using them to drive the expression of fluorescent reporter genes. Afterwards, they will transfect iPS-derived embryoid bodies with plasmids containing these reporters and use fluorescence activated cell sorting (FACS) to insolate cells expressing reporters during various stages of differentiation down the keratinocyte lineage. After isolating iPS-derived keratinocyte precursors, they can then perform real time PCR, western blots, and eventually gene expression profiling to assess the quality of human iPS-derived epithelial tissue.

Iris would like to thank the Amgen Foundation, the Lowry Lab, Dr. Ira Clark, and UCLA SPUR for providing her with this amazing research opportunity!

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Name: Steven He
Home University: UCSD
Class: Junior
Major: Human Biology
Faculty Mentor: Dr. Frank Pajonk

As an UCLA Amgen Scholar, Steven is in Dr. Frank Pajonk’s lab in the Radiation Oncology department, where he’s studying the correlation between proteasome activity and breast cancer cell cycle regulation.

The level of protein expression in cells is determined by highly regulated control of the rate of protein production and degradation. Misregulation of either process can critically affect cellular processes. The 26S proteasome is a highly conserved protein protease responsible for degrading most unnecessary, damaged, or misfolded proteins in mammalian cells. Consequently, the 26S proteasome regulates short-lived proteins that are responsible for basic cellular processes including cell cycle progression, gene expression, apoptosis, DNA repair, and cell growth.

Patients suffering from breast cancer frequently receive chemotherapeutic drugs like taxol, which show maximum efficiency in specific phases of the cell cycle while other drugs like anthracyclins and vinca alkaloids also inhibit proteasome activity. Thus, knowing how this protease is regulated throughout the cell cycle may lead to the design of more effective drug combinations and timing schedules. Steven’s objectives in this study are to explore 1) the possible differences of proteasome activities depending on the phase of the cell cycle, and 2) the regulation of proteasome subunit expression at the transcriptional and translational level. To address the first aim, he will study the proteasome activity of the synchronized cells by analyzing its three main enzymatic processes (chymotryptic, tryptic, and caspase-like) using specific fluorogenic substrates in CSCs and nonCSCs. An assessment of the potential differences between CSCs and non-CSCs will also be performed. Finally, to address the second aim, Steven will use a genomic approach to determine the proteasome subunit composition of each cell line by determining the mRNA expression levels of various proteasome subunits. In order to relate proteasome activity and cell cycle progression to the expression levels of cell cycle regulators, protein levels of p21 and p27 will be studied in parallel.

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Name: Vivian Hecht
Home University: UCLA
Class: Junior
Major: Bioengineering
Faculty Mentor: Dr. Robin Garrell

Vivian’s research involves the development of a more efficient method for performing proteomics research through employing superparamagnetic nanoparticles on a droplet-based microfluidic device.

Droplet-based microfluidic platforms have the ability to simultaneously manipulate multiple small droplets (uL to nL) for a variety of applications. Recent studies have demonstrated the potential of microfluidic devices to significantly improve the speed and efficiency of techniques in proteomics research. The large surface-to-volume ratio of micro and nano-scale droplets enhances the reation rates of enzymatic digestions. Moreover, droplet microfluidic platforms require smaller sample volumes and waste less reagent when compared to conventional methods.

Immobilization of enzymes on superparamagnetic nanoparticles significantly facilitates their separation from a protein solution. Because superparamagnetic substances are not magnetic in the absence of a magnetic field, they can be easily isolated from a solution using a hand-held rare earth magnet and then completely, and uniformly, redispersed. The ease of enzyme separation allows for enzyme recycling, thereby reducing waste and reagent quantities.

Preliminary studies have demonstrated successful digestion of insulin chain-B by trypsin immobilized on superparamagnetic nanoparticles at 37 ºC. Vivian aims to quantify the amount of enzyme attached to her superparamagentic magnetite nanoaprticles and then use the particles to perform enzymatic digestions on a droplet-based microfluidic device.

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Name: Samuel Israel
Home University: Bard College
Class: Senior
Major: Biology
Faculty Mentor: Dr. Todd Yeates

Sam Israel is a fourth year biology and music student at Bard College in New York. In past summers he has worked in Professor Monica Driscoll’s lab at Rutgers University, studying the molecular genetics of neuronal necrotic cell death in C. elegans. As an Amgen scholar at UCLA Sam is investigating the structure of bacterial micro-compartments with Dr. Todd Yeates.

Intracellular microcompartments are primitive organelles found in many different species of bacteria. One microcompartment that is found in all cyanobacteria is the carboxysome. It is a three-dimensional polyhedran known to play an important role in CO 2 fixation. The structure resembles a viral capsid and consists of thousands of hexameric carboxysome shell proteins self-assembled into the molecular faces of the polyhedran. The main carboxysome components in cyanobacteria are the CcmK proteins. Each CcmK subunit binds with five other copies around a six fold axis of symmetry to form a hexagon. These hexamers then bind with other hexamers to form the molecular layers or walls of the carboxysome.

One major obstacle in current studies of the carboxysome is its tendency to fall apart when purified in vitro. This summer Sam will be engineering a more stable carboxysome shell by mutating cysteines into CcmK and forming disulfide linkages between CcmK hexamers. With a strengthened carboxysome, previously impossible spectroscopic studies can be performed revealing new information about the carboxysome and other bacterial microcompartments. This information may provide a framework for targeting microcompartments as a drug therapy in the future.

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Name: Sattar Khoshkhoo
Home University : UCLA
Class: Junior
Major: Bioengineering
Faculty Mentor: Dr. Carlos Portera-Cailliau

Sattar joined Dr. Carlos Portera-Cailliau’s lab in the department of Neurology as a freshman and he has been working there ever since. Sattar studies how each element in the complex neocortical circuit participates in shaping the firing patterns of large ensembles of cortical neurons in mice.

Epilepsy is a disorder that affects more than 3 million people in North America alone. Better symptomatic treatments (e.g., greater efficacy and fewer side effects) for patients suffering from epilepsy are urgently needed. Epileptic seizures are thought to be triggered by abnormally high neuronal excitability and synchronous burst firing within large networks of cortical neurons. Previous studies have shown than the aberrant synchronization of corticothalamic activity leads to the development of epileptics seizures. Some studies point to the fact that layer 5 neurons are the “pacemakers” for network activity in the cortex, but these studies have lacked the unique capability of silencing specific neuronal subsets. By expressing the Drosophila allatostatin receptor in specific layers of the neocortex Sattar can selectively silence groups of neurons in layer 2/3 and layer 5 of the neocortex. Then using direct cell-attached recording and two-photon calcium imaging he can study the changes in network activity caused by silencing layer 5 that was previously identified as the “pacemaker”. Consequently, discovering the roles of different layers of the neocortex can help Sattar identify where in the brain epileptic seizures are generated.

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Name: Jose Matteo
Home University: Florida International University
Class: Senior
Major: Biomedical Engineering
Faculty Mentor: Dr. Jacob Schmidt

At Florida International University Jose studied Respiratory Gated Positron Emission Tomography and its implications on locating and treating tumors in the lung. As an AMGEN scholar at UCLA in Dr. Jacob Schmidt's lab Jose works on Lipid Bilayer Membrane creation and analysis of parameters on the viability and thinning time of said membranes.

Lipid Bilayer Membranes are planar membranes created on a scaffolding material such as Teflon and suspended between two pools of electrolytic fluid. The bilayer arises from a combination of Diphytanoylphosphatidylcholine (DPhPC) suspended in n-decane. The formation of the lipid bilayers requires a specialized process called painting although the use of automated techniques where the membrane is frozen and reconstituted are available. From developing a device to create pores in the Teflon scaffolding, to the parametric analysis of pore size on membrane viability and thinning time the lab seeks to find optimal parameters in membrane formation.

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Name: Meghan McKeon
Home University: Brown University
Class: Senior
Major: Biology
Faculty: Dr. Aldons Lusis

At Brown, Meghan works with Dr. Cynthia Jackson to uncover the mechanism whereby mutations of the gene RMRP result in skeletal dysplasia. To this end, Meghan studies how the introduction of mutant RMRP affects the differentiation and proliferation of murine chondrocytes in vitro. In Dr. Lusis’ laboratory at UCLA, Meghan studies how a specific locus on human chromosome 9p21 correlates with type II diabetes (T2D) and atherosclerosis.

Five genome wide associaton studies have independently identified similar regions on chromosome 9p21 that strongly associate with T2D and atherosclerosis. The implicated region contains no genes, suggesting that its influence on T2D and atherosclerosis occurs through the regulation of genes nearby. The genes CDKN2A and CDKN2B are close to this region of association and have been identified as influential on pancreatic islet cell hypoplasia. Meghan’s efforts will be focused on identifying how transcript levels of CDKN2A and CDKN2B correlate with indicators of diabetes and atherosclerosis in mice. Previously in the Lusis lab, a large mouse population was generated, fed a Western diet to promote atherosclerotic and metabolic disorders, and phenotyped extensively for T2D and atherosclerotic indicators. Adipose RNA was isolated from 300 mice, and Meghan will use quantitative PCR to examine how the levels of CDKN2A and CDKN2B transcripts correlate with the disease phenotypes. Meghan will use the computer programming language “R” to analyze these transcript/phenotype relationships, and she expects to find a significant positive correlation between the expression levels of at least one nearby gene with T2D and/or CAD in the murine adipose tissue.

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Name: Karan Mehta
Home University: UCLA
Class: Junior
Major: Electrical Engineering
Faculty Mentor: Dr. Pei-Yu Chiou

In Dr. Pei-Yu Chiou’s lab at UCLA, Karan is developing a technique involving optical tweezers and magnetic microparticles for 3-dimensional manipulation of individual magnetic nanowires. A few techniques exist for manipulation of individual semiconducting nanowires, including single beam and holographic optical tweezers, but neither of these is applicable to metallic nanowires. The technique being explored involves optically trapping a polystyrene microsphere attached to a magnetic one, which under the influence of an externally applied magnetic field attracts magnetic nanowires in solution; translational and rotational motion can be achieved by translating the optical trap and rotating the external magnetic field, respectively. Manipulation of magnetic nanowires could have a number of interesting applications in biology; for example, a number of recent studies have focused on using electromagnets to exert forces on magnetic nanoparticles attached to cells, and thereby elicit cellular responses in ways that will be valuable in terms of understanding certain aspects of cellular functioning. For magnetic forces to be applied to particles in a localized way (active only over a small region of a cell), magnetic field gradients must be generated over short distances, which is a significant challenge with electromagnets - nanowires naturally induce such localized gradients, however, and therefore, if able to be manipulated accurately, could simply allow for localized exertion of magnetic forces on cells. 

The lab has already demonstrated the ability to manipulate individual nickel nanowires using this technique; during the summer, Karan will work towards characterizing the forces on magnetic particles possible with the technique, as well as continuing to refine the technique such that it can be reliably and efficiently applied. 

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Name: Michelle Riener
Home University: UCSC
Class: Senior
Major: Chemistry
Faculty Mentor: Dr. Neil Garg

From left to right: Neil Garg, Michelle Riener, Kyle Quasdorf

Michelle Riener is a fourth year undergraduate student at UC Santa Cruz. At UCLA, Michelle has been performing research in Neil Garg’s laboratory, working closely with Kyle Quasdorf, a second year graduate student. One of the focuses in the Garg lab is the development of metal-catalyzed reactions to synthesize carbon–carbon (C–C) bonds, the building blocks of organic molecules. These bonds are extremely important to synthesize due to their abundance in natural products, drugs, agrochemicals, commercial dyes, and various materials. One of the most important and versatile methods available for constructing C–C bonds involves organometallic cross-coupling reactions. Although much attention has been given to cross-coupling reactions of aryl halides, the cross-coupling of phenol-derived substrates has been examined to a lesser extent. The use of phenol-derivatives as cross-coupling partners is very attractive because phenols are cheap, readily available, and can be used to direct the installation of other functional groups onto an aromatic ring. Thus, Michelle’s research efforts at UCLA focus on the construction of sp 2–sp 2 C–C bonds by the cross-coupling of unconventional phenol derivatives. Phenol derivatives will be synthesized, and then studied in the nickel-catalyzed Suzuki-Miyaura cross-coupling reaction. Extensive optimization will be done, which will include the screening of various solvents and bases, as well as catalysts. Results of these optimization studies will lead to the identification of the best conditions that can be used to promote these novel cross-coupling reactions

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Name: Stacey Shiigi
Home University: UCLA
Class: Senior
Major: Bioengineering
Faculty Mentor: Dr. Daniel Kamei

As an Amgen Scholar, Stacey works with Dr. Daniel T. Kamei in the Department of Bioengineering, investigating the use of aqueous, two-phase micellar systems in partitioning whole bacteria cells. This partitioning is an appealing method of concentrating bacteria, initially present in aqueous solutions, into smaller fluid volumes.

Bacterial infections of the bladder, kidneys, or other components of the urinary tract are the most common infections in the United States. Complications arising from urinary tract infections (UTI’s) can lead to patient morbidity and are a leading cause of health expenditures, partially due to the expensive and lengthy diagnostic method. This process can require several days, leaving the patient undiagnosed for that duration. The Kamei Lab has been generating two-phase micellar systems with the nonionic surfactant, Triton X-114, to examine the partitioning behavior of bacterial and mammalian DNA and RNA. These systems exploit the chemical properties of nonionic surfactants and their ability to self-aggregate into micelles in aqueous solutions. The solution will separate into a micelle-rich and micelle-poor phase, a process which theoretically drives the hydrophilic compounds, such as DNA and bacteria, preferentially to the smaller volume of the micelle-poor phase. Stacey works on extending the applicability of these two-phase systems to partitioning whole bacteria in urine-like solutions. This methodology could be instrumental in increasing the sensitivity of diagnostic tools: allowing for earlier detection of a UTI and as such, more timely treatment decisions.

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Name: Amy Steinmetz
Home University: Brown University
Class: Junior
Major: Neuroscience
Faculty Mentor: Dr. Xian-Jie Yang

Amy has most recently worked in Dr. Peter Aronson's Pediatric Nephrology lab at Yale Medical School investigating the effects of calyculin on NHE3, a kidney transport protein. Specifically, she examined the protein's phosphorylation state and transport efficiency through Western Blotting and radioactive uptake assays. As a UCLA Amgen Scholar, she will work in Dr. Xian-Jie Yang's lab to determine the spatial and temporal expression pattern of Stimulated by Retinoic Acid 6 (STRA6) in developing mouse retina.

STRA6 is a transmembrane protein whose expression is upregulated in the presence of retinoic acid. This signal molecule is stored as retinyl ester and binds Retinol Binding Protein upon release. The complex circulates until it is recognized by STRA6, which transports the retinoic acid into the target cell. In short, STRA6 is essential in mediating the specificity of retinoic acid targeting on a cellular level. In Dr. Yang's lab, Amy will determine this protein’s expression pattern in the mouse retina throughout development. She will perform immunohistochemistry, with an anti-mSTRA6 antibody kindly provided by Dr. Sun, to section and stain retinas from mice of various developmental stages, ranging from embryonic through adult. This research will indicate when and where the retinoic acid signaling pathway is important during development of the optic system. It will also enable Dr. Yang's lab to generate temporal and spatial conditional knockouts of STRA6, which will be useful in future experiments addressing optic system development and dependence on retinoic acid signaling.

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Name: Tamara Tasoff
Home University : MIT
Class: Senior
Major: Brain and Cognitive Science
Faculty Mentor: Dr. Felix Schweizer

As an Amgen Scholar in Dr. Felix Schweizer’s lab in the Center for Health Sciences, Tammy is studying the effects of pesticides on proteasomes, and its implication for neurotransmission.

The ubiquitin-proteasome system (UPS) is a pathway that is responsible for degrading proteins in the cytosol of all types of cells. Epidemiological, genetic, and biochemical studies suggest that modulation of this system by exposure to pesticides may play a role in a high prevalence of Parkinsons Disease near farms. A prior study in the Schweizer lab found that inhibition of proteasomes causes inactive vesicles to join the active vesicle pool, allowing for increased neurotransmitter release. To further the understanding of this system and its modulation by pesticides, Tammy aims to determine the inhibitory effects of various pesticides on cortical proteasome function. To do so she will assay proteasome function after exposure to the pesticides in cortical cytosol extract. Once the inhibitory potential of each pesticide is determined, she will test the effects of the pesticides on vesicle release in cultured cortical cells. Tammy anticipates that the experiment will further our understanding of the consequences of pesticide exposure.

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Name: Wendy Tseng
Home University: UCLA
Class: Senior
Major: Physiological Science
Faculty Mentor: Dr. Yin Tintut

Since 2006, Wendy Tseng has been working under the guidance of Dr. Yin Tintut under the Department of Medicine in the David Geffen School of Medicine. She has participated in URFP and also URSP as a Brooksfield Atlantic Scholar.

Her ongoing research focuses on oxidized phospholipids regulation of interleukin-6 (IL-6) expression by bone-forming osteoblasts. IL-6 is one of the cytokines involved in stimulating differentiation of bone-resorbing osteoclasts. Previously, Dr. Tintut and colleagues have shown that oxidized phospholipids, which trigger pathogenesis of atherosclerosis, also regulate bone cell differentiation and maturation. In osteoblasts, o xidized phospholipids decrease the expression of osteoblastic differentiation markers. In osteoclasts, they promote potential of bone marrow pre-osteoclasts, although t he mechanism underlying this effect remains elusive. Wendy has found that oxidized phospholipids induce IL-6 mRNA expression and activate IL-6 promoter-reporter constructs in pre-osteoblast calvarial cell line, MC3T3-E1. She has also found that extracellular signal-regulated kinase (ERK) and protein kinase A (PKA) mediate this induction.

This summer, Wendy is continuing to study the regulatory mechanism of IL-6 expression by oxidized phospholipids. She will elucidate the relationship between the signal transduction pathways activated by oxidized phospholipids. She will also determine the involvement and mechanism of transcription factors in mediating oxidized phospholipid activation of the IL-6 promoter. Wendy’s work towards investigating the mechanisms of IL-6 expression will provide a better understanding of the regulatory role of atherogenic phospholipids in bone cells. In addition, the findings may shed light on the prevalence of osteoporosis in patients with cardiovascular disease.

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Name: Jenna Wilson
Home University: Oregon State University
Class: Junior
Major: Bioengineering
Faculty Mentor: Dr. Rachelle Crosbie

In the past, Jenna has worked with Dr. Greg Rorrer at Oregon State University, investigating the viability of the algae Acrosiphonia coalita during bioremediation of the xenobiotic compound naphthalene. She has also worked to optimize biodiesel production from algae with Dr. Ganti Murthy at Oregon State.

At UCLA, Jenna is working with Dr. Rachelle Crosbie in the Physiological Science Department.

The lab’s research involves studying the physiological mechanisms behind muscular dystrophy, specifically focusing on the role of sarcospan. This protein is present in the dystrophin-glycoprotein complex (DGC), which connects the plasma membrane to the intercellular actin cytoskeleton. In people with Duchenne muscular dystrophy, the dystrophin gene is absent. Therefore, the dystrophin protein is missing from the complex, leaving the DGC completely inactive. It has been found the mild over-expression of sarcospan can ameliorate the symptoms of muscular dystrophy by introducing the utrophin-glycoprotein complex in place of the missing DGC, which increases membrane stability in the sarcolemma. Collaboration with Linda Baum, M.D., Ph.D, has lead to the identification of compound 6, which has been found to increase cell membrane stability by modifying cell surface glycosylation and via increasing the expression of sarcospan. In order to explore the mechanisms of compound 6 on dystrophin-deficient primary muscle cells, Jenna will examine the changes in specific protein levels with the application of this drug treatment.

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Name: William Wong
Home University: UCLA
Class: Senior
Major: Molecular, Cell and Developmental Biology
Faculty Mentor: Dr. Steven Jacobsen

From left to right: Ian Henderson, William Wong, Steve Jacobsen

Dr. Jacobsen’s research focuses on characterizing the various factors that control targeting of DNA methylation, using Arabidopsis thaliana as a model. William has been working in Dr. Jacobsen’s lab for a year under the guidance of Dr. Ian R. Henderson and as an Amgen Scholar, he will continue his work in attempting to characterize factors involved in de novo DNA methylation.

Epigenetics refers to the study of heritable changes that are independent of changes in genetic sequence. Cytosine methylation is an epigenetic marker associated with transcriptional repression, commonly used by eukaryotes to regulate gene expression and to silence selfish genomic elements such as transposons. All DNA methylation in A. thaliana is established during a de novo phase by the methyltransferase DRM2, a homologue of the mammalian de novo methyltransferase family Dnmt3. In mammals, Dnmt3-like (Dnmt3L), which encodes a catalytically inactive paralogue of the Dnmt3 family, is required for de novo methylation in vivo. Recent studies have shown that Dnmt3L and Dnmt3a form a tetrameric complex through their respective C-terminal domains. Dnmt3L has been shown to stimulate the catalytic activity of Dnmt3a. Furthermore, there is evidence that suggests that Dnmt3L guides Dnmt3a to sites of de novo methylation by binding to specific histone marks through its N-terminus. DRM3 encodes the catalytically inactive paralogue of DRM2, although it seems to have evolved independently of Dnmt3L; furthermore, DRM3 is only partially required for de novo methylation in vivo. William has shown that the C-terminus of DRM3 binds to DRM2 in vitro. He will further investigate the interaction between the two proteins by generating a plant line with epitope-tagged DRM2 and DRM3. He will then perform coimmunoprecipitation to determine the extent of interaction between DRM2 and DRM3 in vivo. He will also use the doubly epitoped-tagged line to perform immunohistochemical analysis to determine nuclear localization of DRM2 and DRM3 relative to each other. William’s work will hopefully shed light on the factors involved in de novo DNA methylation in A. thaliana.

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Name: Joan Zape
Home University: UC Riverside
Class: Junior
Major: Biology
Faculty Mentor: Dr. Kathy Sakamoto

In the University of California Riverside, Joan first conducted research in Dr. Connie Nugent’s lab studying different protein-protein interactions at the telomere region of Saccharomyces Cerevisae. Joan is currently working on her undergraduate honors thesis in Dr. Laura Zanello’s lab. She is interested in studying the effects of carbon nanotubes on integrin expression in human fetal osteoblasts. As a UCLA Amgen Scholar, Joan conducts research in Dr. Kathleen Sakamoto’s lab in the Division of Hematology and Oncology. Her research project focuses on determining the effects of the drug ABT-869 on leukemia cells and describing the drug’s possible mechanisms of action.

2 kinds of somatic mutations in the FMS-like tyrosine 3 (FLT3) receptor confer the leukemia phenotype. Internal tandem duplications in exons 14 and 15 of the juxtamembrane domain and a missense mutation in exon 20 in the activation loop of the kinase domain both result in the constitutive activation of the FLT3 receptor in the absence of its ligand. Clinically, pediatric patients that harbor these mutations have a poorer clinical outcome. Only 7% of patients carrying these mutations survive while there is a 44% survival rate for patients without mutations in the FLT3 receptor. Thus, it imperative that a suitable drug candidate against leukemia must have a broad range of activity and must be capable of inhibiting mutated FLT3 receptors.

ABT-869 is a multi-targeted receptor tyrosine kinase inhibitor that is capable of inhibiting the Vascular Endothelial Growth Factor receptor family (VEGF) and Plate Derived Growth Factor receptor family (PDGF), which are both involved in tumor angiogenesis and tumor microenvironment modification. Previous studies in Dr. Sakamoto’s lab have shown that ABT-869 inhibited the proliferation of MV4-11 cells carrying FLT3 internal tandem duplications (ITD) through the inhibition of phosphorylation of FLT3. Joan aims to examine the effects of ABT-869 on mutant Baf3 cells. In addition to examining the phosphorylation of FLT3 in mutant Baf3 cells, she will also examine the effects of the drug on downstream targets particularly, PI3K/AKT pathway which is involved in programmed apoptosis of cells. Her work will aid in determining other possible molecules that are targeted by ABT-869 and also which mutant cell lines are particularly sensitive to the drug.

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Name: Shabnam Ziaee
Home University : UCLA
Class: Senior
Major: Microbiology, Immunology and Molecular Genetics
Faculty Mentor: Dr. Eric Vilain

From left to right: Eric Vilain, Shabnam Ziaee, Valerie Arboleda

Shabnam Ziaee, as a UCLA Amgen Scholar, contributes in Dr. Eric Vilain’s lab in the Department of Human Genetics. Shabnam is studying a mouse model of male-to-female sex reversal which occurs in C57BL/6J mice containing the Y chromosome from a different mouse species, Mus domesticus Poschiavinus, Y POS.

Sex reversal is a phenomenon for C57BL/6J- Y POS (B6- Y POS) mice, which develop aberrant ovarian tissue in XY mice. However, Y POS in the presence of the DBA/2J or 129S1/SvImJ (129) genetic background does not show any sex reversal phenotype and develops normal testicular tissue. Using the 129.Y POS offspring from B6.XY POS and 129.XX crosses after 13 generations, the new C57BL/6J.129-Y POS congenic (con) strain was initiated. In the second round of backcrosses between 129.Y POS and B6 female only fully phenotypic male were selected for breeding at each generation. As a result, Dr. Vilain’s lab has identified a 40 megabase region on chromosome 11 that originates from the 129 background and is likely responsible for the observed protection from sex reversal. Using expression analysis, nuclear subcellular localization, and sequence analysis, a candidate gene list was developed, which included two nuclear transcription factors, Tbx2 and Sox15. Both genes are expressed in the developing testes, and sequence variants exist between the C57BL/6J.129-YPOS congenic strain and the B6 strain, indicating a potential role in early sex determination. Shabnam aims to determine if and how Tbx2 and Sox15 affects expression of Sry, a male- determining gene. These results will elucidate the early genetic programs resulting in male sex determination.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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