The URSP Scholarship is awarded to Juniors and Seniors who have a strong commitment to research, and who are completing an honors thesis or a comprehensive 199 project during their senior year.
| Brandon Pham
Brandon Pham is a fourth year student majoring in Microbiology, Immunology, and Molecular Genetics and minoring in Biomedical Research. Since joining Dr. Singh's autoimmunity and tolerance laboratory in Spring 2014, Brandon has been studying mechanisms gender bias occurs in autoimmune disease pathogenesis.
Autoimmune disorders occur when the body’s immune system mistakenly attacks its own healthy tissue. Although there are over 80 types of autoimmune disorders, the most common diseases are rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. In general, autoimmune disorders occur more frequently in women but more severely in men. Although the cause of autoimmune diseases is still unknown, a class of proteins called toll-like receptors (TLRs) has been identified as an important factor that can affect the development of autoimmune disorders. TLRs are important in the innate immune response, which provides a relatively nonspecific mode of attack on pathogens. The function of these receptors is to identify a broad range of pathogens and microbes, as well as a wide variety of other molecules that may cause tissue damage. However, the innate immune response can result in damage to healthy tissue if prolonged. Because this “self-targeting-self” damage is characteristic of autoimmune disorders, TLRs have become a central focus of research regarding the development of such disorders. To investigate the role of TLRs in autoimmune disease, the Singh lab focuses on two TLRs: TLR7 and TLR8. Genes for these TLRs are located on the X chromosomes. Using flow cytometry, qRT-PCR, and immunohistochemistry, the Singh lab hopes to determine whether the double dosage of TLR7 and TLR8 genes, Tlr7 and Tlr8, respectively, alters the responsiveness to the respective TLR ligands in XXF vs. XYF and XXM vs. XYM splenocyte samples.
Following graduation, Brandon plans to pursue a career in the medical field and academic research. He would like to express his gratitude toward the Wasserman Endowment and Goldwater Foundation for supporting his research in immunology. He would also like to thank Dr. Rafael Romero and Dr. Ira Clark of the Biomedical Research Minor for their dedication to promoting undergraduate research. Finally, Brandon would like to thank his mentors Dr. Ram Raj Singh and Dr. Isela Valera for their guidance and support.
| Lillian Peng
Lillian Peng is a 4th year pre-med bioengineering major. She has been working in Professor Dino Di Carlo’s lab since summer of 2014. The Di Carlo lab specializes in microfluidics, which utilizes micro-scale fluid streams and their unique properties to simulate and probe biologic systems. Lillian’s current research project focuses on deformability cytometry, which uses microfluidic methods to deform cells and characterize the mechanical properties of various cell types and cell states.
Currently, cell state is widely assayed via biochemical markers, which requires costly labeling or sample preparation. Biophysical phenotyping is a promising label-free method of assaying cell states such as differentiation and immune activation. Thus far, biochemical and mechanical phenotyping at the single-cell level have only been studied separately. In order to cross-correlate these two parameter types for cellular diagnostics applications and gain insight into the molecular underpinnings of cellular phenotypes, Lillian is exploring a technique capable of performing high-throughput, continuous, single-cell measurements of both mechanical and biochemical phenotype. This technique integrates a microfluidic device for mechanical profiling and an ultra-high-speed fluorescent imaging system for biochemical profiling. Lillian is also exploring the potential of this technique for measurements of the deformability of subcellular compartments as well as real-time analysis of cell deformation.
Lillian would like to thank Dr. Di Carlo, Jonathan Lin, all the members of the Di Carlo lab, and URSP for their continued support of her research endeavors.
| Aditi Newadkar
Aditi Newadkar is a third-year undergraduate student completing her degree in Neuroscience with a minor in Biomedical Research. She has been a part of the Portera-Cailliau Lab for the past three quarters, where she is interested in understanding the learning deficits seen in mice with Fragile X Syndrome (FXS).
FXS is the most commonly inherited form of mental impairment, and nearly 60% of affected individuals have autism or autistic features, and virtually all have tactile defensiveness, a form of sensory hypersensitivity. Fmr1 knockout mice, the best studied model of FXS, show evidence of neuronal hyperexcitability in various brain regions, but the exact neural circuitry is poorly understood. Aditi is interested in understanding whether these differences in neural circuitry manifest themselves in deficits in learning and behavior between Fmr1 knockout mice and wild-type mice. She trains both Fragile X and wild-type mice in learning a simple visual discrimination task under the supervision of her mentor, Dr. Goel, where data suggests that both Fmr1 knockouts and wild-types are able to learn the task, but Fmr1 knockouts require several extra days of training to do so. She is currently also in the process of learning whether or not the primary visual cortex plays a role in the mouse’s ability to perform these behavioral tasks.
After graduation, Aditi aspires to obtain a medical degree, where she hopes that her background in research will provide a different perspective in how she treats her patients. Aditi would like to express her gratitude towards Dr. Carlos Portera-Cailliau for his sincere and excellent guidance in both her research and future career. She would also like to thank Dr. Anubhuti Goel for her superior mentorship and support.
| Emily Miyoshi
Emily Miyoshi is a senior majoring in Neuroscience at UCLA, and after graduation, she intends on pursuing a career in medical research. Emily has been working in Dr. Karen Gylys’ lab since August 2014. She has been studying the neural mechanisms behind Alzheimer’s disease with human brain-derived synaptosomes (resealed presynaptic terminals). Emily completed her major thesis this past spring and greatly appreciates the opportunity to continue her research through URSP. Her project focuses on how tau pathology synaptically propagates throughout the brain in an activity-dependent manner by investigating the proteoform composition and oligomeric state of tau released by synaptosomes. She is also looking at how tau pathology may also spread by the release of exosomes from synapses.
| Manan Mehta
Manan Mehta is a third-year student majoring in Neuroscience. He has worked with Dr. Patty Phelps since August 2014, in close collaboration with graduate student Michael Thornton. A major focus of the Phelps lab is to investigate the role that Olfactory Ensheathing Cells (OECs) play in axonal regeneration after a complete spinal cord transection. OECs are unique glial cells found in the periphery associated with the olfactory epithelium and in the outer layers of the olfactory bulb. After a complete spinal cord transection of the rat thoracic spinal cord, OECs were grafted near the lesion site and appear to support axonal regeneration. Rats that received the OECs have improved in their stepping ability, and have increased axon density in the normally inhibitory injury site. Descending serotonin (5-HT) positive axons are a specific axonal population that can be evaluated for functional connections across the injury site because there are few intrinsic serotonergic neurons in the spinal cord. These serotonergic axons descend from the brain stem motor regions (Raphe) and are vital to the production of coordinated movement. Specifically, Manan is working with OEC- or fibroblast-transplanted spinal rats that also were treated with epidural stimulation and climb training for 6 months.
Manan is currently using fluorescent immunohistochemical techniques to visualize 5-HT-labeled axons that cross the injury site in these rats. A recent advancement in spinal cord injury analysis is 3D visualization of the injury site environment and this is important to understanding the entire architecture of the injury site. Using every 5th section and Neurolucida software, Manan reconstructs the injury site of the rodents that appear to have connectivity across the injury site. After a 3D construction, he works to quantify the regenerative capacity of 5-HT serotonergic axons, post injury with quantitative volume analysis to gain further insight on the behavior at the injury site with axon bundle tracing.
| Dongyi Lambda Lu
My name is Dongyi Lu, and I’m a senior double majoring in molecular, cell, and developmental biology (MCDB) and computational and systems biology (C&SB). Why these two majors? Because I see the universe as poetry; while I can’t read all of it, I would like to immerse myself in the exegesis of the genome. As I just hinted, I’m now applying for a PhD program related to molecular systems biology, and I would like to continue research in this field after I graduate. Other fun facts about me: I’m an aesthete and I love cats.
My senior thesis: Literature has shown interactions between hepatic iron and lipid metabolism, but the connection between them is unclear. In order to elucidate such connection, I’m conducting a genome wide association study (GWAS) on over 100 strains of hybrid mouse diversity panel (HMDP) mice on high iron diet, which caused steatosis in some strains, mapping hepatic lipid concentrations. I will later integrate this with RNAseq and metallomic data and find gene interaction networks. From available data for 60 strains, promising loci have been found for triglyceride (on chromosome (Chr) 1, distinct from the Chr 7 locus mapped for steatosis due to high fat diet) and unesterified cholesterol (Chr15).
| Larry Liu
My name is Liang Yen (Larry), and I am one of the Undergraduate Research Scholars Program
scholarship recipients for the 2016-2017 academic year. Originally from the city of Fremont in
the Bay Area, I am currently a third-year student studying biology at UCLA. Since the end of my
freshman year, I have been member of the Lai Neuro-oncology lab, studying glioblastoma – an
extremely aggressive form of brain cancer associated with a terrible prognosis. My current
research project aims to tackle the effects mutations on the promoter of the hTERT gene, which
codes for the reverse transcriptase catalytic subunit TERT on the human telomerase
ribonucleoprotein complex. Cancer cells generally have higher telomerase expression, and those
with mutations on the hTERT gene promoter show an even more upregulated gene expression.
While the telomeres, also known as the chromosome ends, shorten with each cell division in
normal cells, cancer cells with active telomerase extend the telomeric sequences at the
chromosome ends, preventing apoptosis. Thus, the therapeutic potential of telomerase inhibition
is of great interest. Using Imetelstat, a first-in-class telomerase inhibitor to be used in a clinical
setting, my aim is to determine its efficacy in inhibiting human telomerase activity in vitro using
human-derived glioma cell lines, such as the U87 and LN-18 cell lines.
| Gengming Liu
I am a senior student majoring in Neuroscience and I am particular interested in the functional recovery of the brain after localized damage. I have been working with Dr. Zeiger for the past year in developing a task for mice to assess their brain functions via behavioral measurements.
For this specific project, I will study stroke in mouse barrel cortex, which receives primary sensory inputs from whiskers. I will train the mice to use whiskers in a frequency discrimination task based on a “go/no-go” behavioral paradigm. After learning occurs, I would induce a well-defined and highly localized cortical stroke on the entire barrel cortex. Subsequent rehabilitation and testing will allow me to evaluate post-stroke functional recovery while trans-genetic mouse strain would allow labeling of the neurons responsible for any functional recovery with high cellular specificity and good temporal precision. Combined with histology results and two-photon imaging, behavioral data will be used to confirm the positive effect of immediate rehabilitation on cortical stroke recovery and, further, search for the brain region responsible for the functional recovery in cortical strokes.
| Franklin Liu
Franklin Liu is a third year majoring in Microbiology, Immunology, and Molecular Genetics. Since joining the Yang Lab in Spring 2015, Franklin has been conducting research under the guidance of the Dr. Otto Yang Lab and under the direct mentorship of MD-PhD candidate Aleksandr Gorin. The primary focus of this lab is studying the role of CD8+ Cytotoxic T-Lymphocytes (CTLs) in HIV-1 infection, and current projects are examining why CTL-targeting of certain epitopes is associated with improved outcomes in HIV infection.
HIV-1 is a retrovirus that eventually causes AIDS in infected individuals. CTLs are a class of immune cells that kill virus-infected cells upon recognition of viral antigens via their T-cell receptors (TCRs). CTLs play a critical role in controlling HIV infection, but in most individuals, the CTL response against HIV is not able to fully control the infection as the disease is able to progress to AIDS. One of the main factors that allows HIV to escape CTL-mediated control is “escape mutations” – mutations that arise in targeted viral epitopes that allow the virus to escape CTL recognition. The Yang Lab has recently developed a high-throughput approach to identify all possible escape mutations that HIV can assume under a given CTL. This method has been utilized to understand escape at the SL9 epitope (Gag 77-85), targeting of which is associated with poor control of HIV, and the KF11 epitope (Gag 262-272), which is associated with efficient control of HIV. The Yang Lab aims to expand upon recently obtained results and identify and confirm individual virus mutants of these epitopes that 1) are more fit than the wild type virus but are easily recognized by HIV-specific CTLs and 2) those that are able to escape recognition by multiple CTLs while maintaining replicative capacity. Furthermore, we are investigating the structural basis of how individual variants facilitate escape from a given CTL. The results of these experiments will shed light on how HIV can escape or be recognized by the immune system and can be utilized in future HIV vaccine designs to target the immune response towards regions that HIV cannot escape.
Franklin plans to pursue a career in the medical field after graduating from UCLA. He would like to express his gratitude toward the Gottlieb Endowment, the Judith L. Smith Scholarship, and the Suggs family for their generous support. He would also like to sincerely thank his mentors Dr. Otto Yang and Aleksandr Gorin for their continued kindness, guidance, and support.
| Junjie Lin
Junjie Lin is a fourth-year Molecular, Cell and Developmental major. He has been working under the guidance of Dr. Samson Chow from Molecular and Medical Pharmacology since Fall 2014. Junjie focuses on characterizing the interactions between HIV-1 capsid protein (CA) and integrase (IN) through biochemical analysis such as co-immunoprecipitation and binding assays.
Human Immunodeficiency Virus Type-1 (HIV-1) is a retrovirus that achieves its replication by inserting its viral genetic materials into the host cell genome. It has a protein protective layer consists of capsid protein (CA) forming a core that houses the viral RNA genetic materials and enzymes. To establish a successful infection after entry to susceptible cells, human HIV-1 needs to undergo a controlled disassembly of the capsid core, namely the uncoating process, in the cell cytoplasm so that viral enzymes can work together and prepare for viral genome entering to the host cell nucleus. Subsequently, the viral genetic materials are inserted into the host cell genome through reactions catalyzed by a viral enzyme called integrase (IN). Previous experiments suggested that IN can physically interact with hexameric CA and tubulin CA assembly. Further characterizations of CA-IN interaction were done by examining how individual IN domain interact with assembled CA. A better understanding of IN and CA interaction can elucidate the poorly understood uncoating process and help discover new therapeutic targets for anti-viral therapy. HIV-1 has a rapid replication cycle which renders high mutation rates and hence, high viral genetic diversity. Effective and new anti-viral targets must be pursued fiercely in order to prevent HIV-1 from escaping the established therapeutic scheme. CA alone has emerged as a promising new drug target. Recent reports have identified compounds targeting CA, and they were able to inhibit viral replication by later the kinetics of CA disassembly. Similarly, the CA and IN interaction could emerge as a new therapeutic target that anti-viral strategies can build upon.
Junjie would like to thank Dr. Samson Chow and graduate student Xiaowen Xu for their mentorships and support, as well as the Oppenheimer Endowment for their generous support for undergraduate research.
| Alexandra Libro
CREB-Regulated Transcriptional Coactivator 1 (CRTC1), a transcriptional regulator, localizes to the cytosol during basal conditions, but upon glutamatergic stimulation it becomes dephosphorylated and translocates to the nucleus. In the nucleus, CRTC1 forms a complex with CREB and other transcription factors that binds to cAMP response elements (CRE), resulting in the transcription of genes important for memory. The first part of my project is to investigate how different synaptic inputs such as dopamine and norepinephrine receptor agonists affect CRTC1 translocation. I will be applying TTX and BIC as controls to acute hippocampal slices, a preparation which allows the preservation of physiologically relevant neural circuits in the hippocampus. I will be treating some of the slices with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a glutamatergic AMPA receptor stimulation to drive CRTC1 to the nucleus. The effect of dopamine and norepinephrine on CRTC1 will be investigated by treating the slices with SKF-81,29741(SKF) and isoproterenol (ISO), which are dopamine D1/5 and norepinephrine β-adrenergic receptor agonists, respectively. To perform the immunohistochemistry, for each section I will use Hoechst which will stain DNA to enable visualization of the nucleus, a primary antibody against MAP2 to label neuronal processes, a primary antibody against CamkIIα to label excitatory neurons, and a primary antibody against CRTC1. The second part of my project will be to identify the types of cells in the hippocampus that express CRTC1. I will immunolabel excitatory neurons, inhibitory neurons, cholinergic interneurons, astrocytes, microglial cells, oligodendrocytes, and oligodendrocyte precursor cells in order to elucidate whether CRTC1 is present in the cells and to visualize its subcellular localization. The cells types with CRTC1 localization will be further investigated to determine the effect of neuromodulators on the nuclear translocation of CRTC1. The third part of my project aims to deduce the structure of the CRTC1 protein using circular dichroism. Mass spectrometry of CRTC1 suggests that there are over 50 possible phosphoresidues for CRTC1 (10). Changes in three specific phosphorylation sites of CRTC1 alters its association with different protein partners and translocation, however it is unclear if the structure of the protein is also altered with phosphorylation changes. I will culture HEK 293 cells and transfect them with a plasmid encoding either His-tagged unmutated CRTC1 or His-tagged CRTC1 with three key phosphorylation sites mutated. Using a cobalt affinity chromatography protocol, I will purify CRTC1 for circular dichroism spectrophotometry. This part of my project will not only investigate the structure of CRTC1, but also possible changes in structure due to the mutation of certain phosphoresidues.
| Wei Li
Wei Li is a third year student at UCLA majoring in Chemistry, with a specialization in Computing. She joined Professor Ken Houk's laboratory as an undergraduate researcher in Winter 2016, and has been working on multiple computational projects since.
Her current research focuses on analyzing a Lewis-Acid catalyzed Diels-Alder reaction. Using computational methods, she will analyze the theoretical reaction mechanism, stereoselectivity and catalytic effect. Her previous studies include analyzing a novel synthesis of 2-Ethenylcyclopropyl Aryl Ketones via intramolecular SN2-like displacement of an ester, which is a collaboration with Professor Michael E. Jung's laboratory.
Wei hopes to be a medicinal chemist at a pharmaceutical company. She will be trying to become a research associate after she graduate, but she will also be applying for graduate school as her second choice. Wei would like to recognize and express her sincere gratitude to Mr. O'Connell for his generous donation, Professor Houk and Mr. Peiyuan Yu for their support and guidance.
| Ceejay Lee
Ceejay Lee is a senior majoring in Molecular, Cell and Developmental Biology with a computing specialization and an anthropology minor. She is pursuing both College and Departmental Honors and is motivated towards a career in academic research in the future. With this goal in mind, she intends to further specialize in research of molecular biology by attending graduate school for her future after graduation.
| Nguyen Le
Nguyen Le is a Bioengineering senior undergraduate student with a minor in Biomedical Research. He has been conducting research under the guidance of Dr. Daniel T. Kamei since 2014, focusing on developing a sensitive point-of-care diagnostic device for infectious diseases by combining aqueous two-phase systems and an isothermal nucleic acid amplification test.
The motivation for this project is infectious diseases, which are the leading causes of death worldwide in children and adolescents, especially in developing countries. Currently, the gold standard for detecting infectious diseases are nucleic acid amplification tests, such as the commonly known polymerase chain reaction (PCR). However, its complicated multi-step procedures and requirements for specialized equipment and lab technicians make it unsuitable as a point-of-care detection method.
To address this problem, our lab proposes to develop a one-pot reaction that can combine DNA preparation and amplification into one single step. More specifically, for DNA amplification, we chose to work with thermophilic helicase-dependent amplification (tHDA), a recently-developed isothermal amplification technique that allows DNA amplification to occur at a single temperature. We are also investigating the use of aqueous two-phase systems (ATPS) as a method to purify and concentrate DNA. By combining tHDA and ATPS, we hope to achieve a simple, integrated, easy-to-use, yet highly sensitive DNA amplification system that can achieve a lower limit of detection than commercial tHDA kits alone.
Nguyen Le would like to thank Dr. Kamei, Sherine Cheung, and the rest of the Kamei Lab for the wonderful learning experience in solving real-world medical problems. His experiences in the Kamei Lab have inspired him to pursue an MD/PhD dual degree after graduation and a career in healthcare innovation. Nguyen also would like to acknowledge the Undergraduate Research Center, Undergraduate Research Scholars Program, Mr. O’Connell, and Mr. and Mrs. Rodman for their funding and support.
| Mason Lai
Mason Lai is a fourth-year UCLA undergraduate majoring in Microbiology, Immunology, and Molecular Genetics. His interest in protein structure led him to join Dr. Hong Zhou’s Laboratory in Fall 2014. He is currently studying the highly unusual structure of the Leishmania donovani ribosome, a parasitic eukaryote which is rapidly developing drug resistance to traditional treatments. Leishmania donovani often causes Visceral Leishmaniasis which has an extremely high fatality rate if untreated and can cause epidemic outbreaks in certain circumstances. Current efforts are largely focused on vector control rather than development of new treatments. Due to recent antibiotic resistance in many cases of Leishmaniasis, there is now a great need to develop novel treatments. Ribosomes form the translational center for all life, and as such it is a highly promising target for antibiotics. The native ribosome structure is being compared to a drug-bound Leishmania donovani ribosome to accurately determine the contacts required to cause binding and subsequent inhibition of the parasitic ribosome. Several existing drugs have emerged as promising anti-leishmanial drugs in recent years, which might collectively elucidate the binding requirements for inhibitors. Recent advances in cryo-EM techniques have enabled imaging of the ribosome at high-resolution, which allows for detailed analysis of the many structural interactions with functional and structural significance. Mason hopes to resolve the full structure of the drug-bound Leishmania donovani ribosome in order to identify targets and factors which will guide future antibiotic design.
Mason would like to thank Dr. Hong Zhou for his knowledge, guidance, and support throughout his time in the lab. He would also like to thank the Wasserman Award for their generous funding and support for his research.
| Jennifer Laborada
Jennifer Laborada is a 4th year Microbiology, Immunology, and Molecular Genetics major. She is currently conducting research in the Kohn laboratory, which focuses on developing new therapies for genetic diseases of the blood cells. The laboratory uses ex-vivo gene therapy as one approach, which involves the collection of cells from the bone marrow, enrichment for stem cells, transduction of stem cells to correct the gene defect, and transplantation of the corrected stem cells back into the patient. These corrected hematopoietic stem cells (HSCs) have the capability to differentiate into gene-corrected mature cells and thus provide a continuous source of gene-corrected cells. My research project, in particular, applies this model to a rare autoimmune disease, immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome.
IPEX syndrome is a rare, fatal autoimmune disease caused by loss-of-function mutations in the forkhead box P3 (FoxP3) gene. The FoxP3 gene is essential for production of regulatory T cells (Tregs), which regulate the immune response and prevent autoimmunity. IPEX patients typically exhibit symptoms like diabetes, dermatitis, colitis, and it is fatal shortly after birth. Allogeneic bone marrow transplant (BMT) is a potential treatment option, but immunological transplant complications have limited the success of this strategy. A more promising alternative that Jennifer’s research project explores is autologous BMT with lentiviral gene therapy, which allows genetic correction and transplantation of the patient’s own HSCs. In order to explore the potential of autologous BMT to treat IPEX, we have designed a lentiviral vector with an endogenous FoxP3 promoter and transcriptional control elements, FoxP3 gene, mStrawberry fluorescent reporter, and effective chromatin insulators. We hypothesize that this novel endogenous approach would restore normal physiological expression patterns. After validation of our vector in vitro, the efficacy of correcting HSCs in a clinically relevant murine model of autologous BMT will be explored. If successful, this project may lead to novel clinical trials for treatment of IPEX syndrome. Additionally, there is an unmet medical need for FoxP3 deficiencies with no current approved therapies; thus, results could potentially be applied towards other autoimmune diseases with Treg dysfunction/absence, such as multiple sclerosis and rheumatoid arthritis.
Jennifer would like to extend her most heartfelt appreciation to the Wasserman family for their guidance and support of her research endeavors. Jennifer would also like to thank her mentors Dr. Donald Kohn and MD/PhD student Kate Masiuk for providing a nurturing and friendly environment to conduct research.
| Ritvik Kharkar
I am a senior at UCLA studying Mathematics of Computation and Economics. My primary research interests lie in the field of data science applied to social good. To elaborate, I am interested in and have worked with entities in the public sector including city governments and universities, applying their plethora of data towards improving underlying structures. The aims of these projects have varied, including predicting whether or not a given 911 call will require medical transport and analyzing which courses in various academic majors make up the “core” curriculum. I enjoy very much working collaboratively on my projects and in working with partners outside my areas of expertise to gain more diverse viewpoints.
The project I am currently working on at UCLA is predicting if and when undergraduate students will drop out of their intended major. This project was motivated by the prevalent trends of students entering a university with an intended major, such as Biology, but eventually dropping out due to either the difficulty of the major or the fact that this major was not a good match for the student’s actual interests. I am working, in conjunction with another undergraduate student and faculty mentor, on building machine learning models designed to predict whether a student will drop out of their given major in the next quarter, year, etc. Through an accurate prediction, we will be able to send precious academic resources to these students and thus help them stay in their major, or direct students to a different major, thus saving them time and money.
| Will Jones
Will is currently a fourth year undergraduate majoring in Molecular, Cell, and Developmental Biology. He works in the laboratory of Luisa Iruela-Arispe where he researches endothelial cells. More specifically, Will’s project focuses on developing a better understanding of the roll that Notch signaling plays in maintaining the quiescent state of the mature aortic endothelium when exposed to laminar shear stress; while there has been significant progress in understanding how fluid shear stress contributes to the development of atherosclerosis and inflammation, less is known about the mechanisms through which laminar shear stress promotes endothelial homeostasis. Will plans to graduate from UCLA in the spring of 2017 and to apply to medical school in pursuit of a career in academic medicine. In his free time, Will can be found running, traveling, hiking and spending time with his family and friends. In addition to conducting research in the Aripse lab, Will volunteers in the Ronald Reagan Hospital emergency room where he collects data from patients who are applicable for trauma related research.
| Ruth Johnson
Ruth (Ruthie) Johnson is a fourth-year undergraduate pursuing a degree in Mathematics of Computation and a minor in Bioinformatics. She joined Dr. Bogdan Pasaniuc’s lab during her junior year in 2016. The Bogdan lab develops computational and statistical methods to understand the genetic basis of complex traits and diseases. The lab focuses on methods for integrative genomics, fine-mapping, and heritability. Ruthie’s project focuses on creating a tool to visually summarize an integrative fine-mapping experiment through the visualization of the local correlation structure, functional annotations, associations statistics, and probabilities for Single Nucleotide Polymorphisms (SNPs) to be causal. The goal is that examining this output will enable rapid identification and prioritization of variants of interest for follow-up functional studies.
Ruthie plans to graduate in Spring of 2017 and intends to pursue a PhD in computer science to continue research in computational genetics. She would like to thank Dr. Pasaniuc and all of the members of the Bogdan lab for their support as well as Dr. Eskin for encouraging her research endeavors. Ruthie would also like to express her gratitude to the Boyer family for supporting her and her current research through the Undergraduate Research Scholars Program.
| Cyrus Jin
Cyrus is a fourth year Biochemistry major working in Dr. Steven Clarke’s laboratory. His current project is focused on investigating the relationship between protein arginine methyltransferase 5 and 7 (PRMT5 and PRMT7). After completing his undergraduate degree, Cyrus wants to go to graduate school and then work in the biotech/biopharmaceutical industry.
| Sonia Iyengar
Over the past year and a half, I have worked in the Voskuhl Laboratory as an undergraduate research assistant on projects aimed at elucidating the molecular mechanisms that drive the expression of sex differences within Multiple Sclerosis (MS). MS is an autoimmune disease of the central nervous system (CNS) that leads to neurodegeneration and demyelination. Approximately three million individuals are affected by the disease. Three times as many females are affected due to a more robust immune response, but males experience faster disease progression in the CNS. Both sex hormones and sex chromosomes influence these sexual dimorphisms in MS. My research uses the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), along with the four core genotypes mouse model to observe the impact of sex chromosomes on disease progression without the confound of sex hormones. RiboTag technology is used to isolate and identify sex differences in specific cell types in the CNS. RNA from RiboTag pull-down will be sent for sequencing to identify potential gene candidates and develop targeted immunotherapies for the disease.
| Zhongxun Hu
Zhongxun Hu is a 4th-year student majoring in Molecular, Cell, and Developmental Biology and minoring in biomedical research. Zhongxun Hu has been part of Dr. Amander Clark’s lab since November 2014. The Clark lab aims to understand the cell and molecular basis of germline development and epigenetic reprogramming, with the long-term goal of building stem cell models to improve human reproductive and child health, and to overcome infertility after cancer therapy.
Primordial germ cells (PGCs) are the precursor cells for mature gametes and have the unique responsibility of passing genomic material from generation to generation. During development, proper PGC differentiation results in high quality gametes, which are essential for normal development and future child health. PGCs undergo genome-wide demethylation in two distinct stages. In a previous study in our lab, we discovered that DNMT1 is required in PGCs to prevent precocious meiosis in females and precocious prospermatogonia differentiation in males. Furthermore, we presented evidence to suggest that that DNMT1 is essential for maintaining DNA methylation at imprinting control regions and meiotic promoters prior to E10.5. During cell replication, the patterns of methylated cytosines are maintained by DNMT1, which has affinity for hemi-methylated DNA, and its cofactor ubiquitin-like with PHD and ring finger domain 1 (UHRF1), which is responsible for recruiting DNMT1 to the replication fork during DNA replication. We have demonstrated that although Uhrf1 is repressed in PGCs, DNMT1 loss leads to the loss of methylation at imprinting control regions (ICRs), meiotic genes, and IAP sequences. Hypothesized that the level of Uhrf1 transcript is not detectable but the amount of protein that is present is enough to recruit DNMT1 to the replication fork, or that Uhrf1 is indeed silenced and that DNMT1 has a novel PGC-specific, UHRF1-independent mechanism in maintaining DNA methylation prior to stage 2 DNA demethylation. My project aims to decipher the role of URHF1 in the maintenance of DNA methylation in PGCs.
| Ashley Hope
Ashley is a fourth year undergraduate double majoring in Molecular, Cell & Developmental Biology and English. She has been in the Brigitte Gomperts lab for two years and is currently working to determine the role of cancer cell derived collagen in the pathobiology of small cell lung carcinoma (SCLC).
Lung cancer is the cancer that kills the most people in the world. SCLC is an aggressive and poorly understood histological subtype of cancer which is highly metastatic and chemo-resistant, with a median 5-year survival rate of only 7%. Ashley’s project aims to understand the role of cellular heterogeneity, in particular the specific contribution of mesenchymal-like SCLC cells, to the aggressive and chemo-resistant behavior of SCLC. She will be testing the hypothesis that mesenchymal-like cells in SCLCs behave like fibroblasts and manipulate the tumor extracellular matrix (ECM) by producing collagen. Using a newly published 3D model of SCLC lung cancer, she will treat organoids with cisplatin, the gold standard chemotherapy treatment for SCLC to identify a chemo-resistant population of SCLC cells. Western blotting and immunofluorescence staining will allow for the quantification of collagen production from these cells. Masson’s trichrome stain will be used to visualize the presence of collagen, and immunocluorescent staining to visualization of pro-collagen, collagen type I and IV. Tissue samples from SCLC patients will serve as positive controls. qPCR and Western blot will be used to compare collagen expression, which is predicted to be very high inorder to allow for manipulation of the ECM for rapid metastasis. This project will be important in understanding the molecular mechanisms of a fatal disease, for which little is known.
After graduation Ashley will attend medical school and intends to specialize in oncology. She would like to thank all the members of the Gomperts lab, especially her mentors Brigitte Gomperts and Sarah Dale, for supporting her research endeavors and making her achievements possible.
| Irene Hong
I am a graduating MIMG major that has been conducting research in the lab of Dr. Jeffrey H. Miller in the department of MIMG starting in the summer of 2015. Following graduation, I plan to pursue a career in the medical field and continue conducting research.
My project studies the synergistic interactions between pairs of mutagens using E. coli as the model system and the RpoB gene. When chemical mutagens such as base analogs are incorporated into DNA, mispairing of nucleotides occurs during replication. With an accumulation of mutations, the cell’s repair system becomes compromised, leading to mutagenesis. Four base analogs, zebularine (ZEB), 2-aminopurine (2AP), 5-azacytidine (5AZ) and 5-bromo-2’-deoxyuridine (5BRDU) were examined for their pairwise interactions. We have already examined four chemical mutagens that are used in cancer therapy and found that a combination of two lead to a significant increase in the mutation rate whereas the other two mutagens showed a decrease in the mutation rate. With relative changes in the levels of the four deoxyribonucleotide triphosphates due to the addition of base analogs, the DNA mismatch repair system gets saturated, leading to an increase in mutation rates. By understanding the molecular basis of mutagen synergies, new DNA repair pathways as well as novel pathways of mutagenesis can be discovered. Some epigenetic cancer therapies use combinations of base analogs for their anti-metabolic activities against cancerous cells. With such dramatic increases in mutagenesis frequency observed in the base analog pair, it is pertinent that mutagen interactions be studied extensively prior to clinical use.
| Julia Hiserdot
Julia Hiserodt is a fourth year student majoring in Microbiology, Immunology, and Molecular Genetics, and minoring in Biomedical Research. She has been conducting research in Dr. April Pyle’s laboratory under the guidance of Dr. Pyle and postdoctoral fellow Dr. Michael Hicks since Spring 2015. The Pyle lab is interested in deriving skeletal muscle progenitor cells (SMPCs) from human pluripotent stem cells (hPSCs) to be used to treat degenerative muscle diseases such as Duchenne Muscular Dystrophy (DMD).
Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive muscle degeneration and premature death. Mutations in dystrophin, a protein essential for skeletal muscle stability, cause DMD muscles to become weakened and susceptible to damage. Regeneration is carried out by satellite cells, adult stem cells that differentiate into skeletal muscle in response to injury. In DMD however, the satellite cells exhaust in an attempt to repair the frequent damage, and thereafter, the muscle quickly degenerates. Julia’s current project Julia’s current research focuses on understanding and improving cell survival during engraftment into mdx-NSG mice, the mouse model of DMD, since SMPCs must survive in the initial hours after transplantation in order to regenerate tissue. Cell death is caused by many factors, including the failure to associate with the host niche. To measure cell survival, Julia will create a bioluminescent reporter, which will allow for high-throughput, longitutidinal analysis of cell survival in vivo. Then the host microenvironment will be manipulated using decellularized extracellular matrices from healthy C57BL/6 mice and cell survival factors such as p38i and forskolin to measure their effect on cell survival.
After graduating, Julia plans to attend medical school to become a physician. Julia would like to express her appreciation for Dr. Ira Clark’s guidance during her time in the Biomedical Research minor. She would also like to deeply thank Drs. Pyle and Hicks for their continued encouragement, guidance, and support in her research endeavors and pursuit of her career goals.
| Reem Halabi
Reem Halabi is a senior microbiology, immunology, and molecular genetics student. She has been working at Dr. Black’s lab since winter of 2016. Her research focuses on studying the mechanisms of Rbfox1 function in alternative splicing. Rbfox1 has nuclear and cytoplasmic isoforms. While the nuclear isoform controls the alternative splicing of various target transcripts contributing to synaptic function, the cytoplasmic isoform is thought to increase the stability and translation of its target RNA by binding to the 3’UTR.Rbfox1-knockout mice display neuronal hyperexcitability, which may be in part due to misregulation of Vamp1. Using knockout mice, she investigates how cytoplasmic Rbfox1-regulates Vamp1 through binding to the 3’UTR.. Furthermore, she studies the molecular interactions of nuclear Rbfox1 with hnRNP-M and Matrin3 within the LASR (large assembly of splicing regulators) complex in a tissue culture system using biochemical techniques.
| Katherine Gee
I am a fourth year student majoring in Psychobiology. I joined the Cornea Genetics Laboratory, directed by Dr. Anthony Aldave at the Jules Stein Eye Institute, in Fall 2014. The Cornea Genetics Laboratory focuses on characterizing the genetic basis of corneal dystrophies, which are a group of rare, inherited diseases that result in opacification of the cornea.
My research project focuses on identifying the genetic basis of posterior polymorphous corneal dystrophy (PPCD). Clinical symptoms of PPCD include opacities, bands, and vesicles in the corneal endothelium. Severe visual disability can result from secondary glaucoma or corneal edema. Up to 33% of affected patients require corneal transplantation. PPCD is genetically heterogeneous. Approximately 30% of PPCD cases have been attributed to haploinsufficiency due to truncating mutations or deletions in the zinc finger E-box binding homeobox 1 (ZEB1) gene on chromosome 10. These mutations cause PPCD3. However, the majority of genetically unsolved cases are most likely associated with another locus. The PPCD1 locus is a common support interval shared between three PPCD families that previously demonstrated linkage to chromosome 20. Screening of the coding regions and exon-intron boundaries of positional candidate genes found within the PPCD1 locus has failed to identify a pathogenic mutation. Using targeted region capture of the PPCD1 locus and next-generation sequencing, our group investigated the non-coding regions of the positional candidate genes and identified a novel single-nucleotide variant in the promoter region of the ovo-like zinc finger 2 (OVOL2) gene. Currently, I am using PCR and Sanger sequencing to screen the promoter region of PPCD probands who do not have a ZEB1 mutation for variants. Once the screening has been completed, I plan to follow up with an investigation of the functional impact of the identified potentially pathogenic variant on OVOL2 promoter activity.
After graduation, I plan on applying to medical school. I would like to thank Dr. Anthony Aldave, Dr. Doug Chung, Ricardo Frausto, and the members of the Cornea Genetics Laboratory for their guidance and support.
| Janine Fu
Janine Fu is a fourth year undergraduate student majoring in Biochemistry. She has been conducting research since her sophomore year in Dr. Robert Clubb's lab in the department of Chemistry and Biochemistry. The Clubb lab is a structural biology lab that utilizes multi-dimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, as well as other cellular, biochemical, and bioinformatic methods to investigate the molecular basis of bacterial pathogenesis. Pathogens display and assemble surface proteins that are used for nutrient acquisition from their host. The Clubb lab is interested in these virulence mechanisms as they are possible targets for inhibitor design for antibiotics of Gram-positive bacteria.
Janine is currently studying the structural and biochemical mechanism of Gram-positive bacteria Corynebacterium diphtheriae (C.diphtheriae) pillin assembly. In C. diphtheriae, the pilus is used to attach and infect host cells, causing the disease Diptheria in humans. Sortase enzymes are responsible for covalently attaching these proteins to the bacterial membrane and are involved in pilin assembly. Possible mechanisms for the process have been proposed and her research will further examine the structural and biochemical properties of sortase-mediated protein ligation. By performing high performance liquid chromatography for kinetics analyses and structural characterization of linked pilin intermediates species, she will characterize the steps involved in pilin assembly. This project will identify crucial sortase-intermediate interactions and provide key information for developing inhibitors against these pathogens.
Upon graduating from UCLA, Janine plans to pursue a Ph.D.. Janine would like to thank her mentors Dr. Clubb and Brendan Amer, as well as the Clubb lab for their continued support and guidance. She would also like to express her gratitude to the Wasserman family for their generosity and the URC- Sciences office for their support.
| Zachary Fouladian
My name is Zachary Fouladian. I'm a fourth year MCDB major working in Dr. Lusis' lab in the MIMG department. My project is on understanding the genetics behind congestive heart failure. Currently, I am trying to elucidate the effect of the Adamts2 gene on heart failure phenotypes and other genes that may contribute to heart failure.
| Sierra Foshe
Sierra Foshe is a third year Neuroscience major with a minor in Bioinformatics. She has worked as a research assistant in Dr. Marcus Roper’s Myco-fluidics lab since the summer of 2015.
The ability to cooperate is vital to the survival of many organisms, and cooperation between distinct unicellular organisms is thought to be a precursor to the evolution of multicellular animals, plants and fungi. However, cooperation has its benefits and drawbacks. Factors like division of labor, distribution of resources, and vulnerability to cheating can affect the fitness of cooperating organisms. This project will investigate the mechanisms of cooperation among spores of the model filamentous fungus Neurospora crassa. Comparing the relative germination rates of spores growing in isolation to those growing together in clusters will determine whether proximity to other spores provides a cooperative benefit.
After graduation, Sierra plans to earn her Ph.D. and pursue a career in academic research. She would like to thank Ryan Wilkinson, Wenjun Cai, and Soroush Kahkeshani for their contributions to the project, Dr. Roper for his mentorship, and the Boyer family for their generous support.
| Elisa Dumett
Exposure therapy is known to be an effective treatment for anxiety disorders. However, many patients do not seek treatment or terminate treatment early on due to the aversiveness of the procedure. This problem could be alleviated if exposure could be achieved without participants’ direct attention to their fear. To test this hypothesis, participants will be shown pictures of neutral images followed by mild shocks. This induces fear leaning, which is then reversed during exposure when participants are shown the feared images without any shocks. To control where participants direct their attention, they are asked to preform a memory task with images shown in the center of the screen. Meanwhile, one of the feared images (e.g. dog) appears in the center where they are paying attention, and another feared image (e.g. guitar) appears on the side of the screen where they are not paying attention. The third feared image (e.g. face) is not shown. If unattended exposure works, we expect that in the end, participants will show less fear toward the images of dogs and guitars than of faces. We will use galvanic skin response and heart rate as measures of fear, whereas an electroencephalogram (EEG) will be used to check for hyper-vigilance–increased fear to all images after viewing a feared-image–and visual processing of the visual stimuli.
| Kenneth Chow
Kenneth Chow is a fourth year Psychobiology major and has been working in Dr. Ronald Harper’s laboratory since the winter of 2015. The Harper Lab uses MRI analyses and other neuroimaging techniques to study the neural mechanisms behind various autonomic disorders. Kenneth’s project investigates potential biomarkers and mechanisms behind Sudden Unexpected Death in Epilepsy (SUDEP).
SUDEP accounts for 7.5-17% of deaths in individuals with epilepsy, and up to half of deaths in individuals with intractable epilepsy. The precise physiological mechanisms behind SUDEP remain unclear, but likely involve respiratory and/or cardiovascular dysfunction. Many temporal lobe structures, especially the insular cortices, mediate such autonomic control. Findings also suggest that the occurrence of generalized tonic-clonic seizures (GTCs) may be a significant risk factor for SUDEP. Mammillary bodies are highly implicated in memory processing, and reduced mammillary body volume may be associated with memory deficits in GTC patients. Kenneth’s project involves a MRI analysis of certain autonomic brain structures, such as the insula and mammillary bodies, of patients with GTCs. Neuroimaging software will be used to detect volumetric changes in these brain structures. Kenneth hopes to further elucidate the potential roles that these brain structures may play in the pathogenesis of SUDEP.
Kenneth plans to graduate from UCLA in the spring of 2017 and will attend medical school the following fall. He hopes to continue pursuing scientific research throughout his career, and would like to thank Dr. Ronald Harper, Dr. Jennifer Ogren, and the rest of the Harper Lab for their mentorship, guidance, and support thus far.
| Daguan Chen
I am Daguan Chen, a fourth-year electrical engineer from the Bay Area. I work with Professor Benjamin S. Williams to design high-performance lasers in the terahertz frequency range. Photons of the terahertz region have energy between that of microwave and infrared photons, and have very interesting properties such as excellent detection of water and explosives. My research focuses on designing a metasurface terahertz laser that exhibits electrically-controlled polarization switching.
| Sarah Chang
Sarah Chang is a fourth year Psychobiology major. She began clinical depression and PTSD research in UCLA at the Leuchter Lab during January 2015 under the guidance of Dr. Andrew Leuchter and Michelle Abrams, R.N. The Leuchter Lab focuses on translating developments in neuroscience into treating mental illnesses and disorders of complex human behavior. Her project focuses on the interaction between TMS (transcranial magnetic stimulation) and lamotrigine in patients with Major Depressive Disorder (MDD).
MDD is a widespread, debilitating illness. An emerging neuromodulation technique called transcranial magnetic stimulation (TMS) is a noninvasive and well-tolerated alternative to pharmacologic treatments. TMS produces similar effects of emotion regulation and long-term stability (Janicak et al. 2010). However in the field of neuromodulation, very few studies have investigated interactions between drug therapy and TMS since the treatment is FDA-approved as a monotherapy. Even so, TMS is almost always utilized as augmentation to drug therapy in clinical practice. In this study, we investigate how lamotrigine, an anti-epileptic commonly prescribed in treatment-resistant patients, interacts with TMS in patients with clinical depression over their first course of treatment.
Sarah hopes to pursue a PhD in clinical psychology after graduating from UCLA in Spring 2017. She would like to thank Mr. Lewis and the Ehirsman Endowment for their generous donation and Dr. Andrew Leuchter for creating a friendly, engaging research atmosphere and continuing to support and guide her in all her research endeavors.
| Alex Chan
Alex Chan is a senior majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Drawn by his interest in neural development, Alex joined Dr. Alvaro Sagasti’s laboratory at the beginning of his sophomore year. The Sagasti lab studies the morphogenesis of sensory neurons and skin cells, which together mediate touch sensation. Under the mentorship of graduate student Donald Julien, he is currently using genome-editing technology to identify molecular markers of sensory neuron subtypes in zebrafish.
Somatosensory neurons innervate the skin of vertebrates to detect mechanical, thermal, and chemical stimuli. Proper organization of somatosensory innervation is important for dividing the skin into discrete sensory territories, but the mechanism by which these sensory endings are organized remains unclear. Because zebrafish are transparent, develop externally, and rapidly give rise to a sensory system capable of detecting multiple touch stimuli, they are an ideal model to study somatosensory development.
Rohon-Beard (RB) neurons—a subclass of somatosensory neurons—terminate their axons in the skin of the larval zebrafish. During development, neighboring axons of RBs repel one another, forming a pattern resembling tiles across a bathroom floor, but these repulsive interactions appear to be subtype-specific, since some neighbors tile—or repel—one another, whereas others cross over.
He hypothesizes that subtype specific-repulsion between axonal neighbors suggests that there are multiple tiling subtypes and that these subtypes may be functionally distinct. To identify subtypes, Alex is using a CRISPR/Cas9 nuclease system, a genome editing technology that can be targeted to alter specific genomic loci. Alex is using this system to generate reporters for candidate genes that may label subtypes of somatosensory neurons. Additionally, he is using Cre recombinase-mediated genetic lineage tracing to understand how somatosensory neuron subtypes are specified and arranged during development. By applying these genetic tools, he hopes to identify markers defining somatosensory neuron subtypes, which could provide further mechanistic insight into the regulation of axon tiling.
Alex would like to thank his faculty mentor Dr. Sagasti, his graduate student mentor Donald Julien, and the rest of the Sagasti lab for their support and guidance throughout all of his endeavors. Alex would also like to express his gratitude to URC Sciences, I2URP faculty, Dr. Ira Clark, and the rest of the Biomedical Research Minor Faculty for providing the opportunities and encouragement to pursue his research interests.
| Yash Bhagat
Yash Bhagat is a senior at UCLA majoring in Microbiology, Immunology, and Molecular Genetics and minoring in Biomedical Research. He has been working in the Pajukanta Laboratory under the guidance of Dr. Päivi Pajukanta since winter 2014.
The Pajukanta Laboratory studies genetic, epigenetic, and gene-environment interactions in complex cardiovascular diseases using computational and molecular techniques to find disease-associated genes that could provide potential targets for therapeutics. Currently, Yash is analyzing the molecular mechanism underlying a genome-wide association signal for body mass index in Mexicans on locus 20q13.33. The variants are known to be associated with lower body mass index and lower triglyceride levels in Mexicans, implying potential for identification of genes and discovery of obeso-protective drug targets. We are employing expression quantitative trait loci analysis in addition to capture Hi-C in order to uncover the genetic mechanism at work. We are performing analysis on both upstream regulators and downstream targets for the novel obesity regulating genes implicated by the signal.
Yash plans to graduate with Bachelors of Science and Honors Collegium from UCLA by spring 2017 and aims to pursue an MD/PhD thereafter. He is also involved in other projects in the laboratory, such as the characterization of context-specific expression quantitative trait loci, and Exome Sequencing. Finally, he is also thankful for the generous support that he has received from the Ehrisman Endowment and the Undergraduate Research Scholars Program.
| Hannah Bell
My name is Hannah Bell and I am a fourth year Molecular, Cell and Developmental Biology Major at UCLA with a Biomedical Research minor. I work in the lab of Dr. Peter Bradley in the Microbiology department, where I study the parasite Toxoplasma gondii. My project involves the localization and functional characterization of novel proteins in the Inner Membrane Complex, a parasite specific organelle. I am currently applying to MSTP programs around the country, where I hope to study the cell biology of neurodegenerative diseases. Eventually, I hope to run a lab, work in a neurology clinic, and teach medical or graduate school classes. In my free time, I like to read, hike, and cook.
| Ziyan Zoe Zhu
My name is Ziyan (Zoe) Zhu. I am a fourth year Physics and Applied Mathematics double major and minor in Art History. I am pursuing both College and Departmental Honors. After graduation from college, I plan to pursue a Ph.D. degree in plasma physics. Eventually, I want to become a physics professor who applies knowledge not only to imparting knowledge but also to harnessing the fusion energy and thus solving the world’s energy crisis.
| Yihao Yang
Yihao Yang is a 4th year Biochemistry student at UCLA. Currently, he works in Dr. Kathrin Plath’s group in the Biological Chemistry department studying X chromosome inactivation (XCI) in human pluripotency with human embryonic stem cells (hESCs). In particular, he is interested in understanding the role of a lncRNA XACT (X active coating transcript) in hESCs.
The inactive X chromosomes in primed hESCs are epigenetically unstable, as over time in culture, they lose XIST expression, H3K27me3 histone marks and become partially active. Collectively, these epigenetic changes are termed as erosion. The eroded X chromosomes remain active even after differentiation, which renders female hESCs potentially unsafe for further application. Recent research suggests that X active coating transcript (XACT), a human-specific 250kb lncRNA, is the potential master regulator of this process since it is expressed from X chromosome with very little erosion: neither XIST expression nor X-lined gene expression.
To understand the role of XACT in hESCs, Yihao deleted either the promoter or the entire gene of XACT in primed hESCs with CRISPR/Cas9 technology. Validated by RNA-FISH, female XACT-/- and XACT+/- clonal cell lines were successfully generated. So far, he did not observe rescue of XIST expression from these deletion lines in primed culture or the fibroblast differentiated from them, which implied that the time window of XACT function is limited to the naïve pluripotency where XIST and XACT directly interact. Therefore, he is currently adapting these edited cells to the naive 5iLAF culture and expecting to observe changes in XIST expression patter in the naive hESCs. Additionally, he is working on understanding the spreading pattern of XACT on X-chromosome with RNA Antisense Purification followed by DNA-Sequencing.
| Junjie Xia
My name is Junjie Xia. I am a senior undergraduate student major in Astrophysics at UCLA. Since the spring quarter of my junior year, I’ve been doing research with Prof. Matthew Malkan on the Active Galactic Nucleus’s (AGN) both in vicinity of the Milky Way and at higher red shifts. AGN is a group of galaxies, including Quasars and Seyferts, with large accreting central black holes. With the Nickel 40-inch telescope at the Lick Observatory, we are observing a list of distant quasars with every other week. By measuring the trends of brightness changing, we therefore can calculate the possible structure of the hot gas accretion disks around the central black holes. The other half of our project is to analyze the spatial distributions of emission lines from Seyfert nuclei. Almost all existing spectroscopy of AGN has observed a single location centered on the middle of each galaxy. The largest set of data come from the Sloan Digital Sky Survey (SDSS). Since SDSS uses a 3” fiber diameter, this mixes together an unknown combination of gas ionized by the AGN and also by young stars. This confusion particularly makes the study of Seyferts at redshift larger than 0.3 more difficult. Therefore, it is desirable to study the relation of the emission lines from Seyfert nuclei and their host galaxies so that a common model can be built from the local Seyferts and applied to those at higher redshifts.
| Chloe Wu
Chloe Wu is a fourth year bioengineering student and has been conducting research in Dr. Daniel Kamei’s laboratory since the summer after freshman year. Her research has focused on improving point-of-care diagnostic devices using aqueous two-phase systems to concentrate target biomolecules.
Previous work from the Kamei Lab has demonstrated that aqueous two-phase systems can be used to concentrate targets in a patient sample prior to detection on a lateral-flow immunoassay, increasing the sensitivity of the test by 10-100 fold. While this technology has much potential in achieving early and accurate disease detection in resource-poor settings, initial forms of the device have involved trained personnel mixing patient samples with aqueous two-phase systems, and then applying the solution to the assay. The objective of Chloe’s current project is to eliminate this extra user step, along with sample dilution, by dehydrating the aqueous two-phase components onto paper membranes. This would allow the user to simply place the paper device into a sample. As the sample rehydrates the aqueous two-phase components, phase separation would occur and the target biomolecules would be concentrated into the leading phase which would reach the detection region first.
After graduating, Chloe plans to pursue a PhD in bioengineering. Chloe would like to thank Dr. Kamei and the members of the Kamei Lab for their continued support and guidance, as well as the Undergraduate Research Scholars Program for their generous funding for her research endeavors.
| Bradley Uyemura
My name is Bradley Uyemura. I am a Molecular Cellular Developmental Biology major and am aiming for an M.D./PhD once I finish my bachelor's degree. I grew up in La Cañada Flintridge, California, a small suburban town just northwest of Pasadena. I attended La Cañada High School and involved myself with the school's speech and debate club, pole vaulting, and stem cell research at the Keck School of Medicine at USC. As an undergrad at UCLA, I am the president of Senior Young Buddhist League, an inter-collegiate club of Buddhists that gathers to learn more about Buddhism and connect with other Buddhists. I have also received an Emergency Medical Technician certification in Los Angeles county, become a die-hard soccer fan, and, of course, perform scientific research on campus in Dr. Leanne Jones's lab.
For my research project, I am investigating the role of autophagy, a mechanism of celluar component degradation and recycling by lysozomes, on adult stem cell behavior and maintenance using the Drosophila testis stem cell niche as a model system. Adult stem cells are unique in their ability to renew themselves while having the capacity to give rise to differentiated cell to maintain a tissue or organ such as the skin, heart, gut, and testis. Because of its role in regulating starvation response and protein turnover, autophagy is particularly interesting in the contexts of survival and aging, and may be essential for maintaining a pristine pool of stem cells throughout the lifetime of an organism. My preliminary results indicate that autophagy, regulated by the Autophagy Related Gene 1 (Atg1) kinase, is required for the maintenance and proper differentiation of germline stem cells under both homeostatic conditions and following the stress of a nutrient poor diet.
| Brandon Tsai
Brandon Tsai is a fourth-year undergraduate at UCLA pursuing a major in Microbiology, Immunology, and Molecular Genetics. He joined Dr. Xia Yang’s lab during the winter of his freshman year at the beginning of 2014. The Yang lab investigates the interaction between genetic and environmental risk factors, perturbation of gene networks and molecular networks, and their effect on common metabolic diseases such as, obesity, diabetes, and coronary artery disease. The lab employs an integrative genomics and systems biology approach to analyze large molecular datasets and identify specific causal candidates within networks as targets for therapy.
Brandon’s current research primarily focuses on endocrine disrupters termed “obesogens” and their causal role in metabolic diseases such as cardiovascular diseases, type 2 diabetes, and obesity. However, the molecular mechanisms underlying the disease-inducing effects of obesogens, remain poorly understood. One such obesogen that has captured recent attention is bisphenol A (BPA) due to its widespread prevalence in everyday products. Using the C57BL/6 mouse model treated with BPA, Brandon can observe both phenotypic and genotypic effects from BPA treatment. Phenotypes, including body fat composition, blood glucose, lipids, insulin, and glucose tolerance, will be measured before DNA methylome and transcriptome analyses through Reduced Representation Bisulfite Sequencing and RNA sequencing. Construction of tissue-specific gene networks can then point to key regulators that mediate the molecular toxicity of BPA as well as its effect on metabolic diseases.
| Anna Tao
Anna Tao is a third-year undergraduate student at the University of California, Los Angeles, majoring in Human Biology and Society B.S., under the Institute of Society and Genetics. She intends on graduating in spring of 2018, and plans on furthering her education in medical school.
Anna is involved in the Association of Chinese Americans, the American Red Cross, and is the founding president of the Society for Leadership and Achievement’s UCLA chapter. She volunteers as a Certified Application Counselor on behalf of Covered CA, enrolling individuals into health insurance plans and increasing the health literacy of community members. In the Center for Advanced Surgical and Interventional Techniques at UCLA, Anna is a student researcher under the guidance of Dr. Erik P. Dutson, where she studies and hopes to improve techniques in minimally invasive robotic surgery.
When she is not at lab or in the library, Anna applies her creative eye to photography, decorating her bedroom walls with pictures of past adventures and typography posters of quotes from her steadily growing book collection.
| Daniel Suto
Dj has been involved with the Krantz lab since December of 2014 and is interested in neurotransmission and transport using Drosophila melanogaster as a model system. The Krantz lab integrates molecular biology, fluorescent imaging, and genetics to investigate monoamine transporters. While monoamine release and regulation are often targeted for various pharmaceuticals, some of the aspects of neurotransmission from vesicles remain unclear. Amines can be packaged for release into two types of vesicles: synaptic vesicles and large dense core vesicles (LDCVs). Previous work in our lab has shown the vesicular monoamine transporter (VMAT) localizing to both types of vesicles. The importance of differentiation between these two release sites is a main focus of the Krantz lab because although we are beginning to understand the mechanisms behind vesicle trafficking, the significance of release from LDCVs is unclear. This project specifically targets a microcircuit of Drosophila melanogaster as a genetically tractable model for the downstream effects of release from LDCVs.
| Christine Sun
Christine Sun is a third year at UCLA pursuing a Microbiology, Immunology, and Molecular Genetics major and Bioinformatics minor. She has been working in Dr. Yang’s lab since January 2015. The Yang lab uses integrative genomics and a systems biology approach to study molecular mechanisms behind common metabolic disorders such as diabetes, obesity, and coronary artery disease, analyzing genome-wide, tissue-specific transcriptomic changes to put genomic signals into gene network perspectives.
Christine’s current research is on the sex-specific gene networks of coronary artery disease (CAD). Although there have been previous studies on major CAD genetic risk factors, the mechanisms underlying the gender difference remain poorly studied. Christine’s project is based on the hypothesis that genes coordinate their actions in tissue-specific gene networks instead of functioning in isolation; males and females differ in specific network architecture, which underlies the differential susceptibility to CAD between sexes. She hopes that the sex-specific networks as well as the biological pathways and key regulators involved in these networks will not only provide mechanistic insights into the sex difference in CAD susceptibility, but also offer novel sex-specific targets to facilitate personalized medicine.
After graduating, Christine hopes to pursue a Master’s or PhD in a related field. She would like to thank Dr. Xia Yang, Zeyneb Kurt, and the other members of Yang lab for being so supportive, helpful, and encouraging. She would also like to thank the Boyer family and URSP for their generous support of her research.
| Alexandra Stream
Alexandra Stream is a fourth year undergraduate student, majoring in Microbiology, Immunology, and Molecular Genetics. She is an undergraduate researcher in the laboratory of Dr. Kent Hill. The Hill lab studies the protozoan parasite, Trypanosoma brucei, which is the causative agent of African sleeping sickness and is transmitted through the bite of the tsetse fly vector. Alexandra studies the regulation of social motility in T. brucei. During infection of both the mammalian host and the tsetse fly vector, these parasites are in constant contact with host tissue surfaces. When the tsetse fly midgut-associated life cycle stage of T. brucei is cultivated on surfaces in vitro, parasites engage in social motility. This surface-induced behavior consists of parasites actively assembling in groups and moving collectively outwards from the point of inoculation. To identify possible regulators of social motility in T. brucei, an RNA-sequencing experiment was done to identify genes differentially expressed during social motility vs individual cells in suspension. Candidates identified as upregulated during social motility are investigated by inducible RNA-interference (RNAi) knockdown. Knockdowns are examined for viability and social motility. Some genes whose knockdown results in a social motility phenotype include cyclophilin A (CypA) and an RNA-binding zinc finger protein (ZC3H34). RNAi-mediated knockdown of CypA or ZC3H34 results in delayed social motility compared to non-RNAi controls. To understand these social motility defects, we are looking at propulsive motility of individual cells in the knockdown in suspension culture. This is an important measure because cells with a defect in propulsive motility have been shown to have defective social motility on plates. Further study of these genes may help elucidate the regulatory pathways behind social motility in T. brucei and, more broadly, reveal previously unknown parasite signaling systems. Alexandra greatly appreciates the support of the Undergraduate Research Scholars Program and would also like to thank Dr. Kent Hill, Stephanie DeMarco and other members of the Hill lab for their support.
| Weilin Song
Weilin Song is a fourth year student double majoring in Human Biology and Society and Neuroscience. Since joining the Silva Lab in Spring 2015, Weilin has been studying how different memories are temporally linked in the brain. The Silva lab is particularly interested in the mechanisms behind memory allocation, which is the process by which neurons are recruited to participate in a neural ensemble. Previous studies found that artificially increasing excitability in a subset of neurons increased the chance of these neurons to be recruited into an ensemble. This indicates that memory allocation is not random and is influenced by the intrinsic excitability of neurons. In our study, we wanted to ask if naturalistic fluctuations in excitability might link multiple memories encoded close in time, and how this process might change with age.
Following graduation, Weilin plans to pursue a career in academic medicine. She would like to sincerely thank her mentors, Dr. Denise Cai, and PI, Dr. Alcino J. Silva, for their guidance, encouragement, and support. She would also like to express her gratitude towards the Boyer and Smith Endowment for its generosity in supporting her research in memory and learning.
| Lisa Situ
Lisa Situ is a fourth-year student majoring in Molecular, Cell, and Developmental Biology with a Minor in Biomedical Research. She has been working in the laboratory of Dr. Heather Christofk since October 2015. The Christofk lab is interested in the study of cellular metabolism, including the different biological contexts in which metabolism is reprogrammed. In the last decades, metabolic reprogramming has become increasingly appreciated as a significant hallmark of cancer. Many human tumors display decreased oxygen consumption, even in aerobic conditions, indicating a change in oxidative metabolism. The Christofk lab has found that adenovirus infection decreases oxygen consumption of human breast epithelial cells. Because both viruses and cancers face similar biosynthetic requirements and have been shown to reprogram cellular metabolism in similar ways, virus infection may serve as a simpler model system to more carefully study the metabolic changes that might also be relevant in the cancer context. Lisa’s project focuses on determining the process through which adenovirus decreases oxygen consumption, thus far identifying the interaction between adenovirus gene product E4ORF6/7 and cellular transcription factor E2F-1 as a potential mechanism. Through small hairpin-mediated RNA knockdown or overexpression paired with infection in cultured human epithelial cells, she has studied the effects of E4ORF6/7 and E2F-1 in altering oxygen consumption and modulating expression levels of the genes involved in oxidative phosphorylation. Lisa plans to graduate in Spring of 2017, hoping to pursue a career in biomedical research by applying to Ph.D. programs in the biological sciences. She would like to thank her graduate mentor Shivani Thaker, Dr. Christofk, and all of the members of the Christofk lab for their support, encouragement, and guidance. Lisa would also like to express her gratitude towards the Wasserman Family for graciously supporting her and her project.
| Satvir Saggi
Satvir Saggi is currently a third year undergraduate Microbiology, Immunology, and Molecular Genetics major and has been conducting research in the lab of Dr. Carlos Portera-Cailliau since September 2015 studying stroke recovery
Stroke is the 4th leading cause of death and the most common cause of adult disability in the United States. Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas but the exact mechanisms of such plasticity are poorly understood. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral homotopic cortex, but the data are controversial. Satvir’s group uses optical imaging of intrinsic signals through glass-covered cranial windows in mice to investigate whether the whisker sensory representations are remapped to the spared hemisphere after photothrombotic stroke. Stimulation of the contralateral D2 whisker or all the whiskers can reliably produce strong intrinsic signals in the spared hemisphere in control mice. Our group will investigate whether imaging at multiple acquisition timepoints after stimulation (1.5 – 13s) can reveal the presence of signals related to ipsilateral (contralesional) whisker stimulation after photothrombotic stroke. The presence of whisker sensory maps would suggest then that the contralesional cortex may contribute to functional recovery after stroke. If our hypothesis is correct we can demonstrate that both the spared hemisphere and the peri-infarct cortex play a critical and functional role in postischemic plasticity and recovery.
After graduation, Satvir intends to pursue a medical degree and subsequent research training in preparation for a career in academic medicine and biomedical/clinical research. He would like to thank the entire Portera-Cailliau lab for supporting his research endeavors, both past and present along with Dr. Maie St. John for supporting his clinical research efforts. Additionally, he would like to thank Dr. Romero/Dr. Clark from the Biomedical Research Minor.
| Paul Robinson
Paul Robinson is a third year Physics major from Oakland, CA. He began research in the Alexandrova lab during Fall of his freshman year. There he has since developed new theoretical approaches for understanding chemical bonding in small clusters and in ultra-hard materials. In this role, he has also spearheaded joint theory-experiment collaborations with research groups at several universities. His works have resulted in several publications, and he recently gave an invited talk at the 4th International Conference on Chemical Bonding. Over the past summer, he took a step back from applied theory and worked on methodology development with Professor Eric Neuscamman at UC Berkeley. This academic year, Paul is back with Professor Alexandrova, and is working on unraveling experimentally indeterminable properties of ultra-hard materials. When not researching, Paul can be found singing in the UCLA Chamber Singers.
| Agnes Premkumar
Agnes is a third year undergraduate student in Microbiology, Immunology, and Molecular Genetics with a minor in Biomedical Research. She has worked in the Xing Lab since Summer 2015 and has worked on understanding various levels of transcription regulation that cells utilize. More specifically, she is trying to understand the types of regulation that occur in response to hypoxic conditions.
Under hypoxic conditions, tissues lack sufficient oxygen to perform vital functions. Hypoxic conditions have also been linked to cancer (tumor hypoxia), ischemia (ischemic hypoxia), and preeclampsia (placental hypoxia). It can also aid in cell invasion and cancer metastasis, which inevitably leads to therapeutic resistance and difficulties in cancer. Understanding the cellular response to hypoxia and the mechanism through which homeostasis is restored can allow us to develop effective cancer therapies.
Hypoxia is known to regulate gene expression and induce a cascade of responses in a cell including signal transduction, glycolysis, proliferation, etc. Dr. Xing’s lab proposes that cellular response to hypoxia includes transcriptional and posttranscriptional changes. Agnes will assess various levels of proteins, and mRNA to determine which genes are involved in the cellular response, and will be involved in validating the bioinformatics data gathered.
In the future, Agnes plans to pursue a MD/PhD degree and continue research in medical school. Agnes would sincerely like to thank Dr. Xing and Dr. Lin for providing invaluable support and mentorship. She would also like to give a special thanks to the donors and URC-Sciences for their generosity in funding her research.
| Divya Prajapati
Divya is a second year Molecular, Cell, and Developmental Biology major and Global Health minor. She has worked in Dr. Luisa Iruela-Arispe’s lab since the spring of her first year and currently studies endothelial barrier function and its relevance to tumor cell extravasation.
Endothelial cells line the interior surface of blood vessels to form a physical barrier which selectively regulates substance exchange between blood vessels and tissues. Previously, the Arispe Lab identified VAV3 as a barrier-regulating molecule and characterized barrier heterogeneity in diverse vascular beds. In particular, Divya used immunofluorescence staining and qPCR techniques to assess the consequences of VAV3 knockout and knockdown, respectively, on barrier-related protein localization and gene expression. The Arispe Lab has also identified several pharmacological compounds which enhance endothelial barrier. Through electric cell impedance and extravasation assays, Divya now researches how these compounds may prevent circulating tumor cells from metastasizing by compromising the endothelium. The results of her research can help elucidate tumor-endothelial cell interactions and mechanistic pathways and eventually develop novel therapeutics for cancer metastasis.
Divya would like to sincerely thank Dr. Luisa Iruela-Arispe, her postdoctoral fellow mentor Dr. Georg Hilfenhaus, and the members of the Arispe Lab for their mentorship, support, and kindness. She would also like to thank the UCLA Undergraduate Research Center for encouraging undergraduate research.
| Tara Aitken
Tara is a fourth-year undergraduate student majoring in Neuroscience. She has been a member of Dr. Kate Wassum’s laboratory since February of 2014. The Wassum lab seeks to understand the neural circuitry and neurochemical signaling underlying motivation and addiction. Tara’s current project investigates the role of cholinergic interneurons within the nucleus accumbens core in cue-motivated behavior.
Environmental stimuli influence our daily reward-seeking behavior. Previous research has implicated that dopamine release in the nucleus accumbens core (NAc) is crucial for the excitatory influence of reward-predictive cues on reward-seeking actions, but little is known about the role of other neuromodulatory systems within the NAc. The striatal cholinergic system has been previously implicated in cue-motivated behavior, possibly by terminally modulating dopamine release. Cholinergic interneurons (CINs) are the primary source of acetylcholine acting at those dopamine terminal receptors, and have been previously correlated with motivated behavior, but their role in cue-motivated behavior is poorly understood. Therefore, Tara is investigating the role of NAc CINs in cue-motivated behavior through chemogenetic-mediated inactivation. This technique allows her to selectively inhibit these CINs while rats perform a behavioral task to gain a more complete understanding of the role of these neurons in cue-motivated behavior. She is also investigating the possible role of these neurons in other related behaviors. Understanding the overall role of these CINs in cue-motivated behavior will help reveal a possible neuronal circuit that could become disrupted in food and drug addiction.
Tara would like to thank her faculty mentor, Dr. Wassum, her graduate student mentor, Anne Collins, and the rest of the Wassum lab for their superb support and mentorship throughout her undergraduate career. She would also like to thank the i2 Undergraduate Research Program staff, the Undergraduate Research Scholars Program, and the Gottlieb Scholarship for their support of her research endeavors and academic goals.
| Denise Allen
Denise Allen is a fourth year Molecular, Cell, and Developmental Biology major with a minor in Biomedical Research. She has been working in Dr. William Lowry’s lab since March of 2016, and she previously worked in Dr. Ellen Carpenter’s lab from September 2014 to March 2016.
Rett Syndrome is a neurodevelopmental disease characterized by normal development until 6-18 months of age, followed by rapid developmental regression leading to mental retardation and motor abnormalities. Most Rett Syndrome cases are caused by de novo loss-of-function mutations in the gene for Methyl CpG Binding Protein 2 (MECP2). MECP2 is known to bind methylated CpG motifs in the DNA to facilitate chromatin remodeling, and is therefore believed to play a role in regulating gene expression. However, the specific function of MECP2 and why the loss of MECP2 causes Rett Syndrome is still unknown. We are using an induced pluripotent stem cell model with neurons derived from Rett patient fibroblasts to probe the molecular changes that occur upon loss of MECP2. We have found that MECP2 loss correlates with reduced 5-hydroxymethylation at the ends of chromosomes, upregulation of subtelomeric genes, telomere shortening, activation of cell stress pathways, and cellular senescence. This suggests a novel role for MECP2 in regulating telomere structure and function, and that the loss of this regulation compromises cell health in a way that may contribute to Rett Syndrome. It is also well established that Rett neurons have reduced dendritic branching, suggesting reduced connectivity and function. We have preliminary data showing that this reduction in branching is specifically driven by the upregulation of p53—one of the major regulators of cell-stress pathways that was upregulated in our MECP2 mutant neurons. We will continue to probe the order in which these molecular and cellular changes occur after loss of MECP2 in order to better understand the connection between MECP2 mutations and Rett Syndrome.