Student Profiles Archive - URSP 2009-2010
Here you will find information about past and present students funded through scholarships administered by the Undergraduate Research Center - Sciences. We are proud of the achievements of our research scholars.
Please click on the program year to get information about the supported students, their mentors and their research projects.
| Mr. Ryan Quiroz
Mr. Ryan Quiroz
Mentor: Dr. Yung-Ya Lin
Title: Targeted Magnetic Resonance Imaging of Pancreatic Cancer through Antibody-Conjugated Nanoparticles
Ryan Quiroz is a third year student majoring in Biochemistry. He is a first year MARC student currently working in a physical chemistry lab researching the early detection of pancreatic cancer with magnetic resonance imaging via antibody-conjugated magnetic nanoparticles. He has been a CARE SEM SPUR participant, as well as a CARE Scholar, and plans to apply to a PhD program in pharmacology. He has been with this lab since 2008 under the mentorship of his P.I. Dr. Yung-Ya Lin.
Cancer is now the leading cause of death worldwide, with pancreatic cancer being the hardest to diagnose and treat. Nonetheless, promise for the mitigation of pancreatic cancer comes from early detection through magnetic resonance imaging (MRI). Currently, real hope for abating and fighting this cancer comes from this detection of small, localized tumors, where the cancer can then be surgically removed. Also, due to the fact that pancreatic cancer can exhibit resistance to chemo- and radiotherapy, detecting this malignancy at the earliest possible stage will increase not only the treatment options available but also the survival rate of the patient. This detection can be accomplished using antibody-conjugated Superparamagnetic Iron Oxide (SPIO) nanoparticles capable of binding to these pancreatic cancer cells. These SPIO nanoparticles have an intrinsic magnetic field, shortening the T2 relaxation time of the net transverse magnetization of surrounding water protons, providing negative contrast in the MR image. The enhanced contrast is then used to visually assess the distribution and magnitude of the tumor cells. In order to test the viability and efficiency of antibody-conjugated nanoparticles, anti-CA 19-9 antibodies were incubated with 25 nm NH2-PEG-coated SPIO nanoparticles, utilizing reductive amination chemistry for the coupling. SPIO conjugation was analyzed through particle size determination and protein assay, and cell binding was verified through Prussian Blue iron staining. Optical and in vitro MR images of the cells were also taken for sensitivity and specificity measurements. Ultimately, the conjugation of antibodies to SPIO provides a platform for future research in cancer molecular imaging.
| Mr. Matt Pimentel
Mr. Matt Pimentel
Mentor: Dr. Lily Wu
Title: Macrophages Promote Stress-Enhanced Breast Cancer Metastasis
Matt Pimentel is a 4th year MIMG major, hailing from Hemet, CA. He is a second year MARC student, working in the Department of Molecular & Medical Pharmacology under the direction of Lily Wu. He is currently investigating the role of macrophage colony stimulating factor in immunosuprression. Matt's research career began during the fall quarter of his second year when he found a research project in Steve Cole's lab through the SRP website. Since then, with the support of the URC/CARE cohort, he has received the CARE Fellowship, spent the summer of 2009 at the University of Texas, Marine Science Institute, attended the SACNAS and CAMP conferences, and participated in immunology research at the University of Pennsylvania. Matt will be applying to PhD programs in Fall 2010, and hopes to land in a lab studying immunology or an awesome infectious disease.
Pathological inflammatory conditions such as cancer result in the systemic accumulation of myeloid-derived suppressor cell (MDSC). MDSCs are a heterogeneous population of macrophage-like and neutrophil-like cells with an immunosuppressive phenotype, resulting in T-cell suppression and immune tolerance to solid tumors. Recent clinical and experimental studies suggest that tumor-derived factors such as stem-cell factor (SCF), IL-6, and macrophage colony stimulating factor (CSF-1) promote MDSC accumulation. CSF-1 has recently been shown to induce an anti-inflammatory phenotype in macrophages, however the mechanisms by which this factor modulates MDSC function in tumors remains to be elucidated. The present study will examine the role of CSF-1 in promoting immunosuppressive macrophages in vitro. We hypothesize that treatment of bone marrow-derived macrophages with CSF-1 alone will induce T-cell suppressive macrophages, and will further enhance the immunosuppressive activity of the anti-inflammatory cytokine IL-4. Results from these studies will establish whether the immunosuppressive activities of MDSCs are CSF-1-dependent and provide a basis for new interventions that target CSF-1 as a mediator of immune evasion by solid tumors.
| Mr. Guillermo Milian
Mr. Guillermo Milian
Mentor: Dr. Stephanie White
Project: Modeling Human Autism and Language Impairment Through Developmental Expression of Protein Cntnap2 in Zebra Finches
Guillermo Milian is an entering junior majoring in Integrative Biology & Physiological Science. As an entering MARC trainee he joined Dr. Stephanie White's lab where he is investigating the role's of an autism susceptibility gene in zebra finches. From cellular to behavioral analyses in finches, it is expected to establish a better understanding of human language disorders. Prior to joining MARC and Dr. White's lab, Guillermo was a part of the CARE Fellows/Scholars Program. He spent a year in Dr. Minor's lab determining whether glucose administration following administered stress enhanced rats' ability to develop resilience. He looks forward to applying to PhD programs in Immunology to learn more about the body's defense against disease.
Autism Spectrum Disorder (ASD) is characterized by impairments in communication, social interactions, and behavior. Mutations in contactin associated protein-like 2 (Cntnap2) are associated with ASD and specific language impairment (SLI). Since songbirds share their vocal learning phenotype and analogous neural circuitry with humans they are a preferred model for studying language disorders. Elevated mRNA expression of Cntnap2 in the frontal cortex of developing human brains suggests that Cntnap2 is involved in stenciling circuits that are involved in cognition and language. In this study, we track the expression of protein Cntnap2 in several song nuclei in zebra finches at key developmental stages through immunohistochemical analysis. Preliminary results have shown sexually dimorphic expression of Cntnap2 within song nuclei. In males, Cntnap2 is enriched in the robust nucleus of the arcopallium (RA) and lacking in basal ganglia nucleus area X throughout development. In females, Cntnap2 is enriched in RA early in development but wanes with age.
Additionally, through double labeling with synaptic vesicle protein 2 (SV2), we will investigate whether Cntnap2 is localized to synapses in RA. This will ascertain whether Cntnap2 signal in RA is a product of RA or LMAN cell bodies. The source of Cntnap2 will then be the target for in vivo viral injections of Cntnap2 knockdown constructs, which will then allow us to study changes in neural electrophysiology and in behavior. Establishing the roles of Cntnap2 would allow for better understanding and more effective approaches towards ASD and SLI.
| Mr. Rey Martin
Mr. Rey Martin
Mentor: Dr. Sabeeha Merchant
Research Title: Proteomic and Genetic Analysis of the Zinc Nutrition Response of Chlamydomonas
Rey Martin is a third year biochemistry major and biomedical research minor. He is a first year MARC student, and the biochemistry lab he works in is interested in the mechanisms eukaryotic cells use to maintain trace metal homeostasis. He joined Dr. Merchants’s laboratory fall quarter of his sophomore year and works under the supervision of the postdoctoral researcher, Dr. Davin Malasarn. He has also participated in PEERS and CARE Scholars and plans to go on to a Ph.D. program after college.
In many organisms, zinc is the most abundant transition metal because it functions as a cofactor in a number of enzymes. However, a high concentration of zinc in cells is detrimental to the organism, making it necessary to maintain zinc homeostasis. The mechanisms contributing to homeostasis in eukaryotic cells are not completely understood and so is a subject of research interest. Responses to zinc-deficiency are being studied using the unicellular green alga, Chlamydomonas reinhardtii. For growth in zinc-deficient medium, Chlamydomonas requires the CRR1 gene, previously identified as a copper response regulator. From a previous screen, suppressors of the crr1 phenotype were identified. These strains (called mutants or revertants) grow like the wild-type strain under zinc-deficient conditions. However, unlike the wild-type strain, the mutants constitutively express plastocyanin, a copper dependent protein normally degraded in zinc-deficiency. These mutants can also grow like the wild-type strain under copper-deficiency and are being analyzed for the copper-dependent expression of plastocyanin. The mutants are being placed into complementation groups to assess the number of affected loci and to test the linkage between the original mutation in CRR1 and the new suppressor mutation. Another physical response of wild type cells in zinc-deficiency is the formation of spherical bodies that contain biounavailable copper. Spectroscopy was used to determine that the crr1 mutants also accumulate copper. Copper hyperaccumulation is also observed in all of the revertants. Strains containing the crr1 mutation were stained with CS3, a copper dye, and imaged microscopically. The data obtained suggests the formation of copper granules is CRR1 independent. The proteome of C. reinhardtii is also being studied by comparing the proteins expressed in zinc-replete and zinc-deficient conditions in wild type cells using mass spectroscopy. The soluble protein samples have been prepared and the proteins that accumulate differently in the two conditions will be identified with reference to the proteome derived from the sequenced genome. The results from these studies will provide more information on the pathways necessary for eukaryotes to maintain zinc homeostasis.
| Ms. Jacqueline Kimmey
Ms. Jacqueline Kimmey
Mentor: Dr. Marcus Horwitz
Title: Iron Acquisition via Hemin in Mycobacterium tuberculosis
Jacqueline Kimmey is a fourth year Microbiology, Immunology, and Molecular Genetics major. She is a senior MARC trainee and will be graduating in spring 2011. She starting working in the Horwitz lab in June 2009, in the department of Medicine, Division of Infectious Diseases.
She is currently working to identify the genes responsible for a secondary iron acquisition system in the human pathogen Mycobacterium tuberculosis. She is continuing her work this summer (2010) in the lab, and is very excited about the progress that she has made. She hopes to present at the Keystone meeting on Tuberculosis in January 2011.
| Ms. Raisa Avezova
Ms. Raisa Avezova
Mentor: Mr. Francesco Chiappelli
Funding: Van Trees Scholar
Title: An Immunohistochemical Approach to Test the Psychobiological Mechanism by which Immigration Stress Raises Nasopharyngeal Carcinoma (NpC) Prevalence
Raisa Avezova is a 3 rd year undergraduate student majoring in Microbiology, Immunology, and Molecular Genetics (MIMG). She has a strong passion for learning the ways in which evidence based research can be merged with clinical data to establish a more effective treatment plan for patients. This interest has led Raisa to work under the guidance of Dr. Francesco Chiappelli in his evidence-based, translational research laboratory in the Department of Oral Biology at the UCLA School of Dentistry since her freshman year.
Currently, her project involves a systemic characterization of the psychobiological biomarkers of the stress of immigration for Latino populations. Raisa predicts that the stress of immigration can significantly increase the risk for head and neck cancer in general and nasopharyngeal carcinoma (NpC), cancer of the soft palate, in particular. She will test the hypothesis that Latino immigrants are at high risk for NpC by means of screening archival pathological biopsy material. Raisa's experiments aim to show if the occurrence and progression of NpC can be predicted by means of a panel of molecular tumor and immune biomarkers. Since early biomarker detection is vital to risk evaluation and assessment of progression of disease, it is essential to learn more about the role biomarkers play in the prevention of cancer development.
Raisa hopes to use the knowledge and expertise she gains from her research experience well after her undergraduate career in order to obtain a dual D.D.S/PhD degree in the near future. She would like to thank Dr. Francesco Chiappelli, her encouraging mentor, for all the support and guidance he has given throughout the years. She would also like to express her utmost gratitude to the Rex and Ruth Van Trees Estate for their generous endowment. Lastly, Raisa greatly appreciates the efforts of the URC/CARE office in establishing such beneficial programs and allowing students like herself to be one step closer to achieving their dreams.
| Mr. Paul Chander
Mr. Paul Chander
Mentor: Dr. Gary Mathern
Funding: Alcott Scholar
Title: Synaptic Dysmaturity as a Mechanism of Cortical Dysplasia
Paul is currently working in the lab of Dr. Gary Mathern, where the goal of their research is to elucidate the mechanism behind cortical dysplasia (CD), a condition that alters brain development in utero and results in severe and intractable pediatric epilepsy. In the mature brain, the neurotransmitter, gamma-aminobutyric acid (GABA) has an inhibitory function. However, in the normal developing brain, activation of the GABA-A receptor is excitatory function due to increased intracellular chloride from reduced concentration of chloride exporter KCC2. They hypothesize that CD tissue retains characteristics of prenatal cortical development due to evidence that GABA-1 receptor activation is excitatory. In addition, electrophysiological studies on resected surgical CD human brain slices have demonstrated more GABA relative to glutamate neurotransmission. Since glutamate is a classically excitatory neurotransmitter, this combination of depolarizing inducers is indicative of a hyperexcitable state prone to seizure induction. To test this hypothesis, Paul will be performing Western blots and immunohistochemistry on surgically resected CD and non-CD pediatric epileptic tissue to identify proteins associated with GABA and glutamate synaptic maturity. It is hoped that the findings of this study will support that a potential mechanism of epileptogenesis in CD is cortical immaturity, which will in turn provide a direction for the development of new treatments. Paul would like to thank Dr. Gary Mathern, Dr. Julia Chang, and My Huynh for their steadfast guidance and support. He would also like to express his sincere gratitude to the Silva Family for their generosity and encouragement of undergraduate research at UCLA.
| Mr. Andrew Chao
Mr. Andrew Chao
Mentor: Dr. Barney Schlinger
Funding: Alcott Scholar
Title: Investigating the Masculinizing Effects of Estradiol
Andrew Chao is a fourth year Ecology, Behavior, and Evolution major (EBE) who has been a member of Dr. Schlinger's physiological science laboratory since Winter 2008.
Andrew has been studying the regulatory and developmental role of brain-derived steroids in zebra finches, a species of songbirds. Sex steroids produced autonomously in the brain may have the capacity to direct sex-specific neural differentiation independent of the gonads. Specifically, the maturation of a series of interconnected song nuclei responsible for the production of learned song in male zebra finches seems to be facilitated by the action of endogenous estrogen. Andrew will assess the relationship between steroids levels, neural masculinization, and song learning in developing juveniles, by monitoring the critical period of song circuit development (post-hatchling day 20 to 45) through microdialysis. Forebrain estradiol may facilitate the formation of a major, male-specific projection from HVC (high vocal center) to RA (robust nucleus of the archistriatum). Andrew seeks to understand the role of brain-derived estrogen in sex differentiation in the brain and social behavior.
After graduation, Andrew is planning to attend either graduate school or veterinarian school.
| Ms. Jessie Chen
Ms. Jessie Chen
Mentor: Dr. Elizabeth Sowell
Funding: Sparks Scholar
Title: Longitudinal progression of puberty predicts changes in brain structure, independent of age, in adolescent boys and girls
Jessie Chen is a third year undergraduate at UCLA who is majoring in Neuroscience and minoring in Global Studies. She has been working in Dr. Elizabeth Sowell's lab since fall quarter of 2008 under the guidance of Dr. Jennifer Braman. The Sowell's lab focuses on using different types of magnetic resonance imaging (MRI), such as functional MRI and diffusion tensor imaging, to study normal and pathologic neural development in children and adolescents.
Recently Jessie has been working on several fMRI studies examining differences in brain activation during various language and reading tasks between normal children and those with fetal alcohol syndrome.
Soon she will be focusing her efforts on a longitudinal project studying gender differences in adolescent cortical thinning and correlations between cortical thickness and blood plasma testosterone levels. The project is a collaboration with Dr. Ronald E. Dahl at the University of Pittsburgh, who has provided the Sowell lab with structural MRI and demographics data collected from healthy adolescents at two time points approximately two years apart. This longitudinal study aims to clarify the relationship between pubertal changes and changes in cortical thickness in various parts of the brain including the primary visual cortex, cingulate gyrus, and frontal cortex. The eventual goal is to be able to use any new findings to better comprehend disorders associated with puberty and gender such as depression. Jessie will be processing and analyzing the structural data with Freesurfer and FSL software to extract any significant correlations between pubertal status indicators and cortical thickness.
Jessie is planning to continue working with the Sowell lab through her senior year and plans on doing an honors thesis next year. She would like to thank the Sparks Fund as well as everyone in the Sowell lab for their help and support of her academic endeavors.
| Mr. Fuad Elkhoury
Mr. Fuad Elkhoury
Mentor: Dr. Karen Lyons
Funding: Wasserman Scholar
Title: The Role of Inhibitory Smad7 Protein on Endochondral Bone Formation and its Impact on TGF- b and BMP Antagonism
Fuad Elkhoury is a fourth-year student completing his studies in Molecular, Cell, and Developmental Biology. With an interest in orthopedics and developmental biology, Fuad joined Dr. Karen Lyons's lab in September 2008 and is currently working on his Departmental Honors Thesis investigating the molecular mechanisms behind endochondral bone formation. Specifically, he is studying the role of Smad7 inhibitory protein in the bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-β) pathways in mammalian bone development. BMP and TGF-β play critical roles at various stages of endochondral bone formation, with both regulating chondrocyte commitment, proliferation, maturation, and apoptosis. While there has been much emphasis on delineating the roles of the BMP and TGF-β signaling pathways, little is known about the factors limiting these signaling pathways intracellularly, such as Smad6 and Smad7, so essential for regulating proper bone development. The role of Smad7 in endochondral bone formation has been studied via in vitro models, but its in vivo characteristics have not yet been analyzed. Fuad's project is to explore the Smad7 inhibitory pathway in vivo using a mouse model in which exon 1 of Smad7 is deleted and to investigate the manner through which Smad7 functions with regards to chondrocyte proliferation and differentiation in mice with a mutated Smad7 gene. He will also investigate signaling pathways impacted by the loss of Smad7.
The primary objective of Fuad's project is to better define the limiting mechanism regulating signaling pathways in endochondral bone formation. This knowledge, in turn, will hopefully enable scientists to evaluate whether Smad7 gene expression can be modified in a clinical setting to regulate TGF-β and BMP signaling, which can then potentially create avenues to address various orthopedic diseases and conditions.
Fuad will be graduating in 2010 and is currently applying to medical school, where he plans to continue pursuing his research interests. He would like to thank the Wasserman Family and the URSP program for their utmost generosity and support of his academic and professional endeavors. Fuad also thanks Dr. Karen Lyons, Mrs. Kristine Estrada, and the Lyons Lab for providing him with the opportunity to conduct undergraduate science research and with the guidance to make his research experience intellectually fulfilling and enjoyable.
| Mr. David Foulad
Mr. David Foulad
Mentor: Dr. Maria Graciela Castro
Funding: Alcott Scholar
Title: Immunostimulatory Effect of HSV1-Thymidine Kinase plus Flt3-Ligand on Glioblastoma Multiforme
David is a fourth year Neuroscience major with a minor in Spanish. He has been working at the Gene Therapeutics Research Institute under Dr. Maria Castro since August 2007. Under the guidance of Dr. Castro and Dr. Marianela Candolfi, he studies the effects of therapeutics against the deadly brain cancer Glioblastoma Multiforme.
Glioblastoma Multiforme (GBM), the most common primary brain tumor, has an extremely low survival rate. Current treatments using surgical removal, chemotherapy, and radiotherapy have lacked significant success. As more effective strategies are needed, novel therapies that train the immune system to target the tumor could have a large impact on the treatment of this devastating cancer.
Dr. Castro's lab has recently developed a gene therapy approach that uses adenoviruses (Ads) to deliver certain therapeutic genes directly into the tumor site. The first gene encodes HSV1-thymidine kinase (Ad-TK), an enzyme derived from Herpes Simplex Virus Type 1, which selectively kills dividing GBM cells by converting the systematically administered prodrug glanciclovir (GCV) into a toxic form that halts DNA replication. The second gene encodes Flt3L (human soluble fms-like tyrosine kinase 3 ligand), a cytokine that stimulates an immune response. The combined treatment is effective because the immune cells recruited by Ad-Flt3L can take up the antigens released by the dying tumor cells. In pre-clinical GBM models of large intracranial tumors, the combination of Ad-TK therapy with the immune-stimulant Flt-3L (Ad-Flt3L) elicits long-term survival in over 70% of treated animals. This dual gene therapy treatment not only induces tumor regression and long-term survival, but has also been shown to produce long-term immunological memory. David has been involved in validating the safety of this therapy as support for clinical trials. David's current projects work to elucidate the mechanism of immune response in the brain, and to explain the efficacy of immunotherapy against brain cancer.
David will be graduating from UCLA in Spring of 2010 and plans for a career in medicine. He would like to thank the Silva Estate for their generous scholarship, URC/CARE for providing him with this opportunity, and Dr. Maria Castro and all of the members of the GTRI lab for their guidance and support.
| Ms. Wendy Fujioka
Ms. Wendy Fujioka
Mentor: Dr. Michael Fanselow
Funding: MacDowell Scholar
Title: Propranolol's effect on enhanced memory consolidation in SEFL rat models
Wendy Fujioka is a fourth year Neuroscience major; Asian Languages minor and currently works in the Fanselow lab under the guidance of graduate student Virginia Long of the Psychology Department. She is investigating propranolol as a potential pharmaceutical treatment that may prevent the formation of traumatic memories by targeting the sympathetic nervous system.
Post-traumatic stress disorder (PTSD) is characterized by emotional disturbances, hypersensitivity to stressful situations, recurrent flashbacks. One drug purported to prevent consolidated of traumatic memories is propranolol-hydrochloride. At present, propranolol is widely used as a cardiac medication in the treatment of hypertension and tachycardia. Propranolol is a nonselective beta-adrenoceptor antagonist, as well as a 5HT-1/5HT-2 serotonin receptor-selective antagonist. Previous animal studies have demonstrated that norepinephrine enhances memory consolidation when acting on the basolateral amygdala (BLA); therefore Wendy's studies are focused around how propranolol impairs the emotional enhancement of memory formation using the stress-enhanced fear learning (SEFL) model. In addition, she will be comparing the effects of BLA inactivation using muscimol (GABA-A receptor agonist), PKMzeta, and anisomyosin in the SEFL rat models.
Wendy has many plans for her future, including medical school, teaching, and being a generally fun-loving person dedicated to her God, family, and friends. Working in the Fanselow lab has been a great opportunity to research into a topic of personal interest and would like to thank her mentors Virginia and Dr. Fanselow for all their support and guidance, and Mrs. Carter for her generous support.
| Mr. Christopher Greer
Mr. Christopher Greer
Mentor: Dr. Xinshu Xiao
Funding: Northrop Grumman/Litton Scholar
Chris Greer is a fourth year Biochemistry student. Under the mentor ship of Professor Grace Xiao, Chris has learned to apply computational techniques to study biology. He has been in the lab since winter quarter of junior year.
The research Chris does involves understanding the mechanistic origins of Type II Diabetes (T2D) and Cardiovascular Heart Disease (CHD). There are strong genetic factors at play with these two diseases and the Xiao lab believes microRNAs (small RNAs that regulate gene expression) may play a key role in the genetic association. Chris is also working to identify microRNAs in long non coding genes by computationally characterizing the theoretical structure and conservation of various sequences to produce novel candidate microRNAs.
Chris would like to thank Professor Xiao and the Xiao lab for the opportunity to conduct research and excellent guidance that has been provided. He would also like to thank the Northrop Grumman/Litton Board for the scholarship recognition and funding provided.
| Mr. Richard Hadi
Mr. Richard Hadi
Mentor: Dr. David Krantz
Funding: Alcott Scholar
Title: Regulation of Vesticular Monoamine Transporter (VMAT) in Dopamine Regulation Related Disorders.
Richard Hadi is a third-year undergraduate student majoring in Psychobiology at UCLA. Under the mentorship of Dr. David Krantz and Dr. Hakeem Lawal, he has been conducting research since the beginning of his second year. Currently his research relates to the neurotransmitter Vesicular Monoamine Transporter (VMAT) that may have implications in treatment of illnesses such as Parkinson's Disease.
Parkinson's disease (PD) is the second most common neurological disorder affecting 1% of adults over 65 in the United States. It is characterized pathologically by the loss of dopaminergic neurons in a region of the brain known as the substantia nigra. At the cellular level, PD is characterized by a misregulation of dopamine, a neurotransmitter that relays messages among neurons. VMAT, a protein that regulates the packaging and transport of dopamine for release at the synapse controls cytosolic dopamine content. Cytosolic dopamine has the potential to damage the cell via oxidation and function as a neuroprotectant. Recent epidemiological studies show that individuals with an increase in VMAT function are protected against Parkinson's disease. Richard hopes that by identifying agents/drugs that increase VMAT function, they can similarly serve as effective drugs against PD.
After graduating with a bachelor's degree, Richard plans on attending medical school while continuing with research. He would like to thank his friends and family for supporting him through school, Dr. Hakeem Lawal and Dr. David Krantz for their guidance and patience and lastly, the Silva family for their interest in his success.
| Mr. Charlie Ho
Mr. Charlie Ho
Mentor: Dr. Ken Bradley
Funding: Boyer Scholar
Title: A Chemical Genetic Approach to Studying Anthrax Lethal Toxin
Charlie Ho is a third year Microbiology, Immunology, and Molecular Genetics undergraduate who aspires to become a doctor and a medical researcher. He has been working in the Bradley Lab since the Fall quarter of 2008. One of the Bradley Lab's primary goals is to determine the molecular mechanisms by which anthrax toxin contributes to disease. Charlie's research approaches this objective by identifying and characterizing small molecule inhibitors that protect cells from the effects of anthrax toxin.
Bacillus anthracis is the bacterium responsible for the disease anthrax. It produces two AB toxins, known as lethal toxin and edema toxin, which are responsible for many aspects of disease. Lethal toxin (LT) proteolytically cleaves several members of the MAPKK family, which are crucial components of cell survival signaling cascades, and causes cell death in some sensitive macrophage cell lines.
A chemical library was screened for compounds able to protect mouse macrophages from LT induced death, and Charlie selected one of those many protective compounds for further characterization. Charlie has already uncovered many properties of the compound, including its ability to protect macrophages equally well from increasing doses of LT and its ability to protect cells when removed before LT addition. In addition, he has found that the compound's protective effect on cells is not likely mediated by its manufacturer-reported activity. Recently, he has discovered the drug's ability to alter MAPKK signaling and is currently trying to determine if protection from LT-induced cell death is dependent on this effect.
Charlie would like to thank everyone in the Bradley Lab and especially thank Dr Kenneth Bradley and Eugene Gillespie for their guidance, assistance, and the opportunity to conduct research. He also thanks the Boyer Family for their generous support.
| Ms. Stacy Hu
Ms. Stacy Hu
Mentor: Dr. Ren Sun
Funding: Hilton Scholar
Title:Elucidating the Role of Post-Translational SUMOylation of Hepatitis C Virus NS5B Protein During Viral Replication
Stacy Hu is a third-year student majoring in molecular, cell, and developmental biology. She joined Dr. Ren Sun's lab in the field of Molecular and Medical Pharmacology in spring 2008. Under the guidance of of Dr. Vaithilingaraja Arumugaswami, Stacy is identifying and characterizing the role of SUMOylation of hepatitis C NS5B viral protein.
The hepatitis C virus (HCV) affects an estimated 170 million people worldwide. It is responsible for chronic liver infections that can eventually lead to cirrhosis and hepatocellular carcinoma, and does not currently have a vaccine to prevent its infection. Like other viruses, HCV uses cellular components to complete its life cycle.Viral proteins are functionally regulated by post-translational modifications such as SUMOylation, ubiquitination and phosphorylation. Modification of proteins by small ubiquitin-like modifiers (SUMO) results in altered protein stability, localization and transcriptional regulation. NS5B, a vitral RNA-dependent RNA polymerase, contains a canonical amino acid sequence corresponding to SUMOylation binding motifs. Stacy's project is to analyze the modification of HCV NS5B protein by SUMOylation and understand its effects during HCV replication. Characterizing and understanding the role of the post-translational modification will provide information regarding regulation of HCV genome replication. This in turn will help tailor new therapeutic approaches to combat the deadly viral infection.
Stacy would like to thank Dr. Ren Sun, Dr. Vaithi Arumugaswami and all of the members of the laboratory for their mentorship in her research endeavors. She would also like to emphasize her gratitude for Diane A. and Henry H. Hilton for their generous support.
| Mr. Brian Ichwan
Mr. Brian Ichwan
Mentor: Dr. Arnold Berk
Funding: Lau Scholar
Title: Next Generation Helper Dependent Hybrid Epstein-Barr Adenovirus Gene Therapy Vector
Brian Ichwan is a fourth year Microbiology, Immunology, Molecular Genetics (MIMG) major and has been conducting research under the guidance of Jordan Moberg Parker and Dr. Arnold J. Berk in the department of MIMG for almost a year. He was initially working on determining the optimization and infectivity of gene therapy vector Ad5/35.FRT, but has now been working on improving the Epstein-Barr virus/Adenovirus (EBV/Ad) hybrid gene therapy vector. The Epstein-Barr/Adenovirus hybrid vector allows for long-term transfer of transgenes, without the issues that arises with viral integration methods, through the attachment and segregation of the vector episome with the host cell chromosomes. Previously it has been shown that our EBV/Ad vector has been able to maintain long term Luciferase expression in immune deficient mice for over 52 weeks, but dramatically lost expression in immune competent mice. It has been shown that the Cytomegalovirus (CMV) promoter and the yellow fluorescence protein (YFP) that are found in our current EBV/Ad vector may be the cause for the loss of vector in immune competent systems.
Brian's independent research project has been to clone a new generation EBV/Ad hybrid vector without YFP and with a ubiquitous CAG promoter in place of CMV. He will then compare long-term expression of the new generation EBV/Ad vector with the old hybrid vector.
Brian would like to thank Jordan Moberg Parker, Dr. Sean Gallaher, and Dr. Arnold J. Berk for their guidance. Also he would like to thank Dora W. and Standley K. Lau for their generous funding.
| Mr. Samuel Irving
Mr. Samuel Irving
Mentor: Dr. Carla Koehler
Funding: Wasserman Scholar
Title: Developing New Probes to Study Protein Import into the Mitochondrial Intermembrane Space in Mammalian Cells
The mitochondria are membrane bound organelles that catalyze a number of essential reactions necessary for eukaryotic cell viability. The majority of the genes necessary for proper mitochondrial biogenesis and function are located for in the nuclear genome. These proteins are translated in the cytosol but are destined for the mitochondrial outer membrane, intermembrane space (IMS), inner membrane, or the matrix. Specifically, the IMS has an oxidative folding pathway and proteins are imported in the reduced form. Once inside the IMS, a sulfhydryl relay system (Erv1 and Mia40) forms transient disulfide bonds with the reduced proteins, accepting electrons and shuffling them to the electron transport chain or molecular oxygen. Recently, mutations in Erv1 have been linked to a human disease, mitochondrial myopathy. The goal of my project is to study molecular mechanisms of this pathway, with the goal of obtaining insight into how defects in this pathway lead to disease. The objective of my project is to determine whether small molecule inhibitors also inhibit the function of human Erv1. For example, the inhibitors are expected to block protein import and impair mitochondrial respiration. Long-term, these inhibitors will be tested in zebrafish to determine if we can recapitulate the mitochondrial myopathy.
| Ms. Xiao Wen (Lisa) Jiang
Ms. Xiao Wen (Lisa) Jiang
Mentor: Dr. Robert Clubb
Funding: MacDowell Scholar
Title: The Development of a Cellulosome Display System
Lisa Jiang is a fourth year Biochemistry Major at UCLA and has been working since April 2008 as a member of the Clubb lab in the Department of Chemistry and Biochemistry. Under the guidance of Dr. Clubb, Scott Robson, and Tim Anderson, she has been developing a system to selectively display proteins on the surface of Bacillus subtilis.
This system will use sortase enzymes commonly found in gram-positive bacteria. We are constructing an experimental system that expresses Sortase A from Bacillus anthracis (BaSrtA) in the safer model organism, B. subtilis. B. anthracis and Staphylococcus aureus are two human pathogens that use sortase enzymes to attach proteins to their surface. Sortase enzymes are involved in pathogenesis and aid in cell adhesion to the host. Sortase performs a transpeptidation reaction where the substrate protein (the protein to be attached to the cell wall) is first cleaved at a sequence specific site and then covalently attached to the cell wall. I have constructed B. subtilis strains, modified to express this sortase, BaSrtA, with FLAG tag to improve the expression and detection of BaSrtA. We are currently in the process of optimizing the expression of the sortase through the display of glucanase A cellulase enzyme on the surface of B. subtilis. We hope to determine the impact of cell wall attachment on cellulase activity. In the future, we want to display artificial cellulosomes that could efficiently degrade cellulose enabling efficient production of biofuels.
Lisa is extremely thankful for the encouragement and support she has received from Dr. Clubb, Scott and Tim. Lisa would like to thank the Clubb lab for their guidance and contributions. She would also like to express her sincere gratitude to J.W. & Nellie N. MacDowell for their generosity and URC for their support and kindness.
| Ms. Danielle Kay
Ms. Danielle Kay
Mentor: Dr. Rachelle Crosbie
Funding: Hilton Scholar
Title: The Role of Akt Signaling in the Amelioration of Dystrophy and Promotion of Muscle Regeneration
Danielle Kay is a 3 rd year Physiological science major from New Orleans, Louisiana. She has been conducting research on Duchenne muscular dystrophy in Dr. Rachelle Crosbie's lab since Fall quarter 2008.
The dystrophin-glycoprotein complex (DGC) is a series of integral and peripheral membrane proteins localized at the sarcolemma and provides mechanical stability during muscle contractions. Dystrophin deficiency results in the loss of the entire DGC, leading to Duchenne muscular dystrophy (DMD), characterized by myofiber necrosis and cycles of degeneration and regeneration. Previously, Akt pathway activation in dystrophin deficient mdx mice before pathology onset was shown to stimulate skeletal muscle hypertrophy, stabilize the sarcolemma by upregulating proteins of the utrophin-glycoprotein complex, and induce growth of new myofibers. Danielle's current research aims to show that Akt transgenic overexpression in mdx mice after the onset of pathology is not only protective, but rescues fibers from degeneration through UGC upregulation and myofiber regeneration. Akt overactivation may have therapeutic benefits for muscular dystrophy patients.
After graduating from UCLA, Danielle plans to attend medical school and continue her support of the muscular dystrophy community. She would like to sincerely thank Dr. Crosbie, Michelle Kim, and the members of the Crosbie lab for their guidance and support. She would also like to thank URC/CARE and the Hilton fund for supporting her research.
| Ms. Jane Kim
Ms. Jane Kim
Mentor: Dr. Hong Wu
Funding: MacDowell Scholar
Title: Cooperation between Pten loss and b -catenin activation in promoting murine prostate cancer
Jane Kim is a fourth-year Molecular, Cell, and Developmental Biology (MCDB) major with minors in Spanish and Biomedical Research. She has been working in Dr. Hong Wu's laboratory since Fall 2008 and plans to pursue a career in medicine and translational research.
Prostate cancer (CaP) is a leading cause of death among men in the United States. In its early stages, CaP can be treated successfully with radical prostatectomy and/or radiation therapy. For advanced disease, however, hormone ablation therapy typically fails, leading to castrate resistance, metastatic disease, and reduced survival. Studies have implicated both Wnt/ β-catenin signaling activation and PTEN tumor suppressor loss in late-stage CaP. Moreover, both are associated with stem-cell regulation. Since cancer stem cells (CSCs) are postulated to serve an important role in the onset of castrate resistance, it has been evaluated whether Pten loss and β-catenin activation can cooperate to enhance CSC function and, therefore, CaP progression. To achieve this, a CaP mouse model with prostate-specific Pten deletion and β-catenin activation has been developed in the lab. To examine stem/progenitor cell content, intracellular lineage markers (e.g. p63) and surface markers (e.g. CD49f) were used to identify the "LSC" stem/progenitor cell subpopulation, recently defined as Lin -Sca-1 +CD49f high. CD44 has also been used as a key marker, as it has been recently reported to enrich for normal prostate stem cells in mouse and human systems. Through immunohistochemistry and FACS analysis, it has been found that there is considerable cooperation between Pten loss and β-catenin activation in promoting expansion of p63 +, LSC +, and CD44 + cells. Compared to mutants with either Pten deletion or β-catenin activation, enhanced content of this subpopulation correlates with marked enhancement of CaP progression. In vitro stem cell assays (e.g. free-floating prostate spheres, non-adherent prostate spheres), RT-PCR, and Western blot analyses are currently being done to evaluate how Pten loss and β-catenin activation may cooperate to regulate CSC self-renewal.
Jane would like to thank Dr. Hong Wu, Dr. David Mulholland, and the members of the Liu/Wu lab for their support and mentorship as well as the Macdowell Estate and UCLA URC/CARE for their contribution to undergraduate research.
| Mr. Jun Kim
Mr. Jun Kim
Mentor: Dr. Benjamin Wu
Funding: MacDowell Scholar
Title: Investigation of mechanisms behind higher drug resistance in a novel three-dimensional cancer tissue culture
Previously, we developed a novel three-dimensional in vitro model in which U251 (glioma cell line) spheroids were incorporated into 3D poly(lactic-co-glycolic) acid (PLGA) scaffolds. Our result showed that 3D polymeric scaffold system led to much higher drug resistance than monolayer system, especially with cells pre-cultured as spherical aggregates having the highest IC 50 value, the drug concentration at which fifty percent of the cells are viable. In this study, we will explore the model further to elucidate more clearly the mechanisms behind the higher drug resistance shown by 3D polymeric scaffolds seeded with spheroids. Other studies have shown that tumor cells grown in three-dimensional models, such as scaffolds and spheroids, tend to show reduced inducibility to apoptosis and this may allow cells to exhibit increased resistance to drugs and radiation. Furthermore, it is widely accepted that one of the major differences between two-dimensional and three-dimensional in vitro systems is the hypoxic environment created by lack of oxygen diffusivity in three-dimensional systems, which may lead to apoptosis in cells. We hypothesized that in three-dimensional culture systems, tumor cells will develop resistance to hypoxia, and this will eventually lead to higher drug resistance.
| Mr. David Kirakossian
Mr. David Kirakossian
Mentor: Dr. Aleksey Matveyenko
Funding: Alcott Scholar
Title: Effects of Insulin Pulsatility on Glucose and Lipid Metabolism in Hepatocytes
David Kirakossian is a fourth year undergraduate student majoring in Physiological Science. He is currently applying to medical school and hopes to become an endocrinologist. David began researching in Dr. Peter Butler's lab, whose focus is diabetes research, under the mentorship of Dr. Aleksey Matveyenko, during the fall of 2007.
The underlying cause of diabetes appears to be a decrease in β-cell mass in the pancreas. A primary consequence of decreased beta-cell mass in both type 1 and type 2 diabetes is a decrease in insulin secretion. The mechanism subserving impaired insulin secretion is reduced amplitude of insulin secretory bursts.
Primary metabolic abnormalities of diabetes include hyperglycemia and hyperlipidemia in both fasting and post-prandial states. These, in turn, lead to increased hepatic glucose production, as well as increased secretion of very low density lipoprotein triglycerides. The mechanism by which a decrease in pulsatile insulin secretion leads to these increases remains largely unexplored. David is examining the gene expression of proteins that are important for glucose and lipid metabolism in the liver. He is using Q-PCR techniques to compare gene expression levels in wild-type rats to those in HIP rats, a model for type 2 diabetes. David is studying enzymes such as glucokinase, glucose-6-phosphatase, phosphoenolpyruvate carboxykinase (PEPCK), and acetyl-CoA carboxylase, as well as others in order to determine if any significant changes in gene expression occur due to hepatic insulin signaling. His aim is to characterize physiological and molecular effects of insulin pulsatility that are critical to the pathophysiology of diabetes.
David is grateful to Dr. Matveyenko and Dr. Butler, as well as his colleagues at the Hillblom Center for their support. He would also like to thank the Silva family for sponsoring him and the URC/CARE office for making this possible.
| Mr. Rameen Moridzadeh
Mr. Rameen Moridzadeh
Mentor: Dr. Volker Hartenstein
Funding: Boyer Scholar
Title: Investigating the role of JAK-STAT and Notch signaling in Drosophila melanogaster Intestinal Stem Cells of the posterior midgut
Rameen is a fourth year undergraduate majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Under the tutelage of Dr. Shigeo Takashima and Dr. Volker Hartenstein, Rameen has been researching the intestinal stem cells (ISCs) of the Drosophila melanogaster midgut since his freshman year. Although the mammalian intestinal stem cell (ISC) niche has been relatively well characterized, serving as an exemplar of niche function and regulation, the preliminary studies of adult Drosophila midgut ISCs leave several questions of fundamental importance unresolved. While the presence of ISCs in the adult midgut is well-established, neither the origin of the adult ISCs nor the existence of midgut stem cells in earlier developmental stages is determined. To this end, Rameen has conducted a differential gene expression report across the development of the midgut to establish unique markers for cluster cells. In late larval stages, numerous clusters of approximately six cells appear in the posterior midgut. Rameen has determined cluster cells are divided into two putative populations: stem cells, which express a STAT92E-GFP reporter for JAK-STAT activity in all the larval cell clusters, and transit amplifying (TA) cells. Interconnected with the ISC and TA populations are the enteroendocrine cells, which require nuclear localization of Prospero transcription factor. Rameen is also investigating the role of Notch signaling in the fate specification of the ISC and enteroendocrine cells. In the future, he hopes to apply his findings as a researcher to clinical work as a physician. Rameen offers his sincerest thanks to the Hartenstein lab for their continual support in his academic and research endeavors. He would also like to thank both URSP and the Boyer Fund for supporting his research.
| Mr. Jonathan Nattiv
Mr. Jonathan Nattiv
Mentor: Dr. Joseph Watson
Funding: Sparks Scholar
Title: Variations in Glutathione-Related Gene Expression in a Mouse Model for Parkinson's Disease
Jonathan is a fourth year undergraduate Neuroscience student and plans on pursuing a career in medicine. In his first year at UCLA he completed Dr. Watson and Dr. Levine's course, Neuroscience: The Brain Made Simple: Neuroscience in the 21st Century. It was this course that sparked his interest in the Neuroscience degree. He has worked under the guidance of Dr. Joseph Watson since his second year at UCLA, investigating the correlation between oxidative stress in the brain and Parkinson's Disease.
In the Watson Laboratory, Parkinson's Disease is investigated with over-expression of α-synuclein as the marker for disease. Over-expression of α-synuclein protein has been correlated with neuronal hypersensitivity to oxidative stress, leading to exhaustion of intracellular reductant systems' ability to manage reactive oxygen species (ROS). The reductant system of interest here is the Glutathione (GSH) pathway. Reductant systems such as Glutathioine serve to maintain a favorable reduced environment across brain tissue in order to minimize oxidative stress induced by ROS.
In this investigation, Jonathan will be analyzing the variations in gene expression of proteins in the GSH pathway after the perfusion of mice frontal lobe cortical slices in artificial cerebral spinal fluid (ACSF) for varying times. Specifically, he will be using a perfusion chamber to treat the samples with the ACSF and running RNA agarose gel and micro-chip array analyses in order to quantify the variations in mRNA gene expression product. Through this study, he hopes to elucidate the variations in GSH product as a function of the time course of Parkinson's Disease progression.
| Ms. Amy Ngan
Ms. Amy Ngan
Mentor: Dr. Ivan Lopez
Funding: Sparks Scholar
Title: Detrimental effects to the mice hearing organ after mild chronic exposure to carbon monoxide (a major component of tobacco smoke)
Amy Ngan is a fourth year undergraduate majoring in Political Science. She has been conducting research under Dr. Ivan A. Lopez in the Surgery Department (Division of Head and Neck) at the David Geffen School of Medicine at UCLA since October 2008.
Dr. Lopez's laboratory studies the effects of miniscule Carbon Monoxide poisoning (concentrations similar to the levels of second hand smoking) on the inner ear and cerebella of rats, mice, and humans. It has been recently found in their laboratory that specific proteins are up-regulated in the brain after mild chronic CO exposure (neuroglobin and superoxide dismutase type 2). These proteins may prevent or attenuate the detrimental effects of CO and tobacco components and oxidative stress in stroke or cardiovascular disease.
Amy is currently doing real-time quantitative PCR array profiling to investigate the expression of specific genes affected by the generation of oxidative stress after CO exposure. Using this technique, she will be able to analyze the gene expression of the inner ear and isolate the genes which are either up or down regulated due to oxidative stress. This research will help Dr. Lopez's laboratory to determine which genes-proteins are affected by tobacco smoke, thus helping understand the process by which the ear deteriorates during CO poisoning.
Amy will be graduating from UCLA in the Spring of 2010 and applying to Medical School. She would like to thank her mentors Dr. Ivan Lopez and Dr. John Edmond for their continued guidance and support. She is also very grateful for becoming a recipient of the Sparks Fund which has given her renewed confidence in her undergraduate research career.
| Mr. Raymond Ngo
Mr. Raymond Ngo
Mentor: Dr. Yung-Ya Lin
Funding: Wasserman Scholar
Title: Virus-Induced Aggregation of Magnetic Nanoparticles for Use in Detection Imaging
Raymond Ngo is a third year undergraduate majoring in biochemistry. He has been working in Dr. Yung-Ya Lin's laboratory in the Department of Chemistry and Biochemistry since Fall 2008, studying the aggregation of magnetic nanoparticles to develop a detection method that can be used for a multitude of small particles, including viruses.
Superparamagnetic iron oxide (SPIO) magnetic nanoparticles may serve as a molecular switch when conjugated with specific antibodies, assembling an aggregate when exposed to the presence of the desired antigen. The cluster produces a change in the spin-spin relaxation times in the MRI signal when imaged, allowing for the specific detection of various small targets, such as viruses or proteins. This project will be using the avian influenza virus, H5N2, as a target to test the viabilities of this application. A phantom model can be created using biotinylated-SPIO, making it possible to conjugate the nanoparticles to streptavidin. To confirm these clusters, dynamic light scattering is used to observe the sizes of the particles before and after the two are introduced in solution. An increase in size thus confirms the induced formation of biotin-avidin aggregates. The large aggregates can then be used to develop novel pulse sequences that can be used in molecular resonance imaging. By creating these new scanning methods, the newfound knowledge can provide for the future detection as well as the production of highly sensitive assays of a large variety of small particles through the use of protein sensors and targeting antibodies.
| Ms. Kristin Owyang
Ms. Kristin Owyang
Mentor: Dr. Julian Martinez
Funding: Hilton Scholar
Title: The role of pico, Drosophila MRL protein, in regulating growth
Kristin Owyang is a fourth year undergraduate earning her major in Molecular Cell and Developmental Biology and minor in Biomedical Research. She began conducting research under the guidance of Dr. Julian Martinez-Agosto in the fall of 2008. She is studying the role of pico, the Drosophila MIG-10/RIAM/lamellipodin (MRL) protein, in regulating growth.
Attaining proper tissue and organ size requires tight control of signal transduction pathways that regulate growth. Studies of these pathways have uncovered numerous mechanisms of growth regulation. However, several components of these pathways remain uncharacterized, and we do not fully understand how signal transduction pathways communicate to coordinate growth regulatory mechanisms. The Martinez-Agosto laboratory studies various growth signaling pathways using Drosophila melanogaster as a model organism. This work provides insight into the causes of genetic syndromes associated with aberrant growth, including overgrowth syndromes and cancer.
Kristin plans to attend graduate school to further her studies of cell and developmental biology. She would like to thank everyone in the Martinez lab for providing continuous support and guidance. She would also like to thank URC/CARE for encouraging undergraduate research and the Hilton Fund for their financial support.
| Mr. Vijay Patel
Mr. Vijay Patel
Mentor: Dr. Frank Laski
Funding: Alcott Scholar
| Mr. Ryan Ponec
Mr. Ryan Ponec
Mentor: Dr. Luisa Iruela-Arispe
Funding: Alcott Scholar
Title: New Insights on the Lesser Known Hemogenic Endothelial Site: Mesenteric Blood Islands
Ryan Ponec is a 4 th year Molecular, Cell, and Developmental Biology major and Biomedical Research minor at UCLA. He works in the lab of Dr. Luisa Iruela-Arispe, studying the emergence of hematopoietic stem cells in a mouse model system. He is a recipient of the UCLA Regents Scholarship and has participated in the American Heart Association Undergraduate Student Research Program, the UCLA Undergraduate Research Fellows Program, and the UCLA Amgen Scholars Program.
During development, the emergence of hematopoietic stem cells (HSCs) occurs over a period of days in several locations. Intra-embryonic vascular sites, which include the aortic gonado-mesonephric region as well as the vitelline and umbilical arteries, have been characterized as independent sources of HSCs. These cells are derivatives of the endothelium. Using a mouse model system, members of the lab have observed a unique phenomenon in the vitelline artery where HSC aggregates appear to leave the vasculature and enter the surrounding tissues. Using a Cre-lox reporter system to specifically label endothelial cells and their HSC derivatives with a fluorescent marker, Ryan is working on establishing an imaging system where this budding process can be observed in real time. In addition, he will work on characterizing the role of Notch-1 in HSC emergence using an endothelial specific Notch-1 knockout mouse.
| Ms. Catherine Pourdavoud
Ms. Catherine Pourdavoud
Mentor: Dr. Peter Bradley
Funding: Lau Scholar
Title: Localization and Function of a Novel Rhoptry Effector Protein (ROP 10072) in Toxoplasma gondii
Catherine Pourdavoud is a third-year undergraduate student majoring in Neuroscience. She is a past participant of the PEERS and NGGSRI research programs. She began conducting research in Dr. Peter Bradley's laboratory (MIMG) in Fall of 2008.
Dr. Bradley's lab studies Toxoplasma gondii, an obligate intracellular parasite which causes central nervous system disorders in immunocompromised individuals and birth defects in congenitally infected neonates. After entering the cell, T.gondi is able to hijack the host cell through the release and action of specialized enclosed structures called secretory organelles. One of these organelles, the rhoptries, release proteins into the host cell that are vital for formation of the parasitophorous vacuole. It is hypothesized that ROP 10072, identified as a novel rhoptry protein, is an effector protein required for optimal invasion and survival of the parasite within the host cell while hiding from the patient's immune system.
The specific aim of Catherine's project is to determine the role of ROP 10072 in invasion and survival by localizing it within the human host cell and identifying the host cell protein(s) that it modifies. She has amplified and expressed the 10072 coding region ectopically in Human Embryonic Kidney Cells (HEK293s) via PTP-tag fusion. Catherine has obtained a stable clonal cell line of the PTP-tagged fusion protein and has used the two-step PTP tandem affinity approach in attempts to isolate 10072 and any interacting partner. Since initial small-scale PTP purifications of ROP 10072 have been problematic, Catherine is currently troubleshooting this strategy and will utilize an alternate strategy employing the Strep/Flag tandem affinity approach if PTP purification proves unsuccessful. Once co-precipitating proteins/protein complexes have been identified, Catherine will be able to further study any protein-protein interactions as well as the phenotypic changes in parasite growth when the host interacting partner(s) of 10072-mature is absent from infected cells. Assessment of the localization of ROP 10072 as well as identification and understanding of its human host targets and function will aid in determining how this protein enables Toxoplasma to take over its host cell, revealing key insights towards the ultimate control of Toxoplasmosis.
Catherine plans on attending medical school after she graduates and looks forward to the day when she is both clinician and researcher, dedicating her life to serving her patients. She would like to deeply thank the Bradley Lab, especially Dr. Bradley, for giving her this exciting opportunity and for their genuine and continuous support, patience, and guidance. She would also like to thank her parents, family, and close friends for their unconditional love and encouragement of her passions, and the Lau Foundation and URC/CARE for their generous scholarship and for making such an important contribution to the academic and scientific research successes of UCLA students.
| Ms. Ann Quan
Ms. Ann Quan
Mentor: Dr. Natik Piri
Funding: Oppenheimer Scholar
Title: Quantitative Analysis of Retinal Ganglion Cells in Experimental Glaucoma by Immunolabeling Rbpms
Ann Quan is currently a third year undergraduate student, majoring in Psychobiology. After interning at an Ophthalmologist's office two summers ago, Ann had the opportunity to volunteer, learn, and "scrub in" during eye surgeries in the operating room. Fascinated with the intricacies and details of a specific surgery, trabeculectomy, performed to treat Glaucoma, Ann decided to pursue extensive research in that field. Glaucoma is an eye disease caused by increased intraocular pressure (IOP) resulting from malfunctioning of the eye's drainage structure. Under the guidance of her faculty mentor, Natik Piri, and senior scientist, Jacky Kwong, since Fall 2008, Ann has participated in research that is aimed towards understanding the reasons leading up to retinal ganglion cell death in glaucoma. Ann analyzes gene expressions that help to better understand retinal ganglion cell apoptosis, bringing us closer to preventing cell death in glaucoma.
The title of her project is Quantitative Analysis of Retinal Ganglion Cells in Experimental Glaucoma by Immunolabeling Rbpms. The objective of this project is to evaluate the progressive loss of retinal ganglion cells in glaucoma through topographical and quantitative analysis of retinal ganglion cells, which have been immunolabeled with a novel marker called RNA Binding Protein Multiple Splicing (Rbpms) in the rat retina after intraocular pressure elevation.
Retinal ganglion cells (RGCs) carry the final neuronal output of the vertebrate retina by collecting visual signals from the two preceding layers of nerve cells, bipolar and amacrine cells, and transmitting this information to the brain. The death of retinal ganglion cells (RGCs) and degeneration of their axons in the optic nerve are the cause of vision loss in various optic neuropathies, including glaucoma. Left untreated, elevated IOP levels can cause permanent damage to the optic nerve, leading to irreversible vision loss. To evaluate the RGC loss in experimental rodent models of glaucoma, these cells are commonly labeled by injection of tracers such as FluoroGold (FG), dextran tetramethyl rhodamine (DTMR), or DiI into areas of the brain that are targeted by RGCs, primarily SC, or by exposure of the axons in the optic nerve to these dyes.
The laboratory recently characterized expression of Rbpms, or hermes, in the retina and demonstrated that Rbpms is specifically expressed in retinal ganglion cells. The lab's quantitative studies supported that the use of anti-Rbpms antibodies is applicable to analyze the numbers of RGC bodies, independent of their connectivity to central target areas. In glaucoma, it is believed that damages to RGCs occur at the axonal level and RGC bodies may survive even without connectivity. However, the mechanism leading to the progression of axonal and cell body degeneration in glaucoma is largely unknown. Understanding the progression rate of axonally damaged and intact retinal ganglion cells may help to further explore the novel treatment for glaucoma.
| Mr. Maha Rahim
Mr. Maha Rahim
Mentor: Dr. Tatiana Segura
Funding: Boyer Scholar
Title: Non-viral Gene Delivery in Fibrin Hydrogels
Fibrin hydrogels have been used extensively as scaffolds for tissue engineering because fibrin is a naturally occurring polymer that allows for cell attachment and growth. It is generally agreed that for regeneration of complex tissues additional biochemical signals are needed within the gel. DNA delivery is a powerful approach that introduces biochemical signals to tissue engineering scaffolds through the delivery of genes encoding for bioactive proteins. However, gene delivery from fibrin scaffolds is currently inefficient. The Segura laboratory developed an approach to introduce DNA nanoparticles into hydrogels without aggregation and high activity. In this study, gene transfer inside fibrin hydrogels containing DNA nanoparticles was characterized. The goal was to discover an optimal set of parameters for efficient three-dimensional gene transfer in fibrin hydrogels. DNA nanoparticles were formed mixing the cationic polymer polyethylene imine (PEI) with DNA. The PEI-to-DNA ratio, measured in terms of moles of amines divided by moles of phosphates (N/P ratio), as well as the cell density inside the hydrogel, affect the transfection efficiency to fibroblast cells. High gene transfection was achieved by incorporating nanoparticles with a N/P ratio ranging from 7 to 9, observed by high amounts of expressed protein and a large number of live and proliferating cells. Increasing cell density does not appear to largely increase transfection, since the number of live cells and amount of cell proliferation decreases as the number of cells encapsulated increased from 50,000 to 250,000. Hydrogels with effective gene delivery may have long-term benefits for regeneration of tissues in vivo.
| Mr. Joseph Rodrigues
Mr. Joseph Rodrigues
Mentor: Dr. Stephen Smale
Funding: Ehrisman Scholar
Title: Characterization of the evolutionary divergence of the NF- κB family of transcription factors by binding affinity analysis
Joseph Rodrigues is a third-year undergraduate student majoring in Microbiology, Immunology and Molecular Genetics (MIMG). Since Fall 2008, he has conducted research in the lab of Dr. Stephen T. Smale, where he is studying evolutionary difference between members of the NF- κB family of transcription factors. He has previously participated in the Biomedical Sciences Summer Enrichment Program and CARE Scholars Program.
The Smale Lab is interested in elucidating the global mechanisms regulating the transcriptional activation of pro-inflammatory genes. The NF- κB transcription factor family plays a key role in the gene regulation of the innate immune system. The correct regulation of NF- κB has been shown to be necessary for preventing cell apoptosis and inflammatory autoimmune disorders. Past research in the field has focused on the signal transduction pathways leading to activation of NF- κB by the phosphorylation and degradation of its inhibitor, I κB. However, the NF- κB family's role at the transcriptional level has not been extensively studied. The five family members form homo- and heterodimers to interact with distinct sets of genes. Two of the family members—c-Rel and RelA—have C-terminal transactivation domains and a highly conserved N-terminal Rel Homology Region (RHR). Although c-Rel and RelA have the same DNA binding domain residues contacting highly similar DNA consensus sites, the Smale Lab has determined that 46 unique residues within the DNA binding domain of the RHR determine gene activation specificity.
To further understand the NF- κB family, we are exploring the importance of its evolutionary divergence. We hypothesize that the evolution of the immune system necessitated its divergence to five family members. Analyzing the divergence in function between c-Rel and RelA will lead to insight into the importance of the divergence of specific regions within the proteins throughout evolution. Initially, functional changes will be studied by looking at evolutionary differences in binding affinity to consensus and non-consensus probes using EMSA off-rate analysis. For this analysis, c-Rel and RelA will be purified from various organisms ranging from invertebrates such as lamprey to mammals such as mice and humans. Results may give insight into the mechanism and significance of the variant structure and function of the members of the NF- κB family.
Joseph would like to thank Dr. Smale and all the members of the lab for their help, patience, and guidance. He would also like to thank the Ehrisman fund for their generous support. Joseph plans to pursue an MD/PhD degree in hopes of making a significant contribution to both advancing the knowledge of biological processes and developing novel ways to treat human diseases.
| Ms. Anna Sahakyan
Ms. Anna Sahakyan
Mentor: Dr. Benjamin Bonavida
Funding: Wasserman Scholar
Title: Characterization of Inhibitors of Yin Yang 1 (YY1) and Their Effect on Transcription and Expression as well as Sensitization of Cancer Cells to TRAIL-mediated Apoptosis.
Anna Sahakyan is a senior majoring in Microbiology, Immunology, and Molecular Genetics. She is a transfer student from Pasadena City College. She has been a student in Dr. Bonavida's lab since January of 2009. After graduating Anna plans to attend graduate school to become more thoroughly involved in research.
Cancer cells can become invulnerable to certain therapeutics by means of gaining resistance. This is a rather serious problem as it leads to recurrence of the disease. Dr. Bonavida's lab is concerned with the investigation of the molecular mechanisms of tumor resistance to therapy, as well as the reversal of resistance and induction of apoptosis (programmed cell death) in tumor cells. Anna's independent project is to characterize potential therapeutic molecules that can possibly inhibit the transcription factor Yin Yang 1. YY1 is a transcriptional repressor of the death receptor DR5. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) binds DR5 and signals the cell to commit apoptosis. YY1 over-activation in certain tumors leads to reduced DR5 expression making cancer cells unresponsive to the TRAIL-induced apoptosis. Therefore, if one ore more of these potential inhibitors could suppress the YY1 activity, resistant cells could become sensitized to TRAIL-mediated apoptosis. Anna tests the effects of these potential YY1 inhibitors in human prostate or melanoma cell lines.
Anna would like to thank Dr. Bonavida for his advice and guidance, as well as the lab members for their support. She would also like to give special thanks to Dr. Baritaki, the postdoctoral fellow in the lab, for her help and inspiration.
| Ms. Claire Sampankanpanich
Ms. Claire Sampankanpanich
Mentor: Dr. Ren Sun
Funding: Oppenheimer Scholar
Title: Characterizing the Interaction of Murine gammaherpesvirus 68 Open Reading Frame 34 and Poly(C) Binding Protein 1
Claire Sampankanpanich is a fourth-year student of Molecular, Cell, and Developmental Biology. Under the guidance of graduate student Shaoying Lee and faculty mentor Dr. Ren Sun, Claire is characterizing the interaction of Murine gammaherpesvirus 68 Open Reading Frame 34 and Poly(C) Binding Protein 1.
Epstein-Barr virus and human herpesvirus 8 belong to the Gammaherpesvirinae subfamily and are important human pathogens involved in tumor development in epithelial, hematopoeitic, and endothelial cell cancers. Gammaherpesviruses characteristically establish lifelong latent infection, persistently counteract host immune responses, and undergo sporadic lytic replication in compromised host immune systems. Herpesvirus genes mediating the lytic cycle are temporally classified into immediate-early, early, and late expression kinetics. While the lytic cycle has been thoroughly studied, regulation of late gene expression after DNA replication is not well understood. Previous studies identified Murine gammaherpesvirus 68 (MHV-68) ORF34, a viral trans factor required to stimulate late gene promoters after viral DNA replication during lytic infection. From cellular-viral PPI Y2H screens, ORF34 was found to interact with cellular poly(C) binding protein 1 (PCBP1), which belongs to the hnRNP family of RNA- and DNA-binding proteins. Preliminary findings indicate that PCBP1 overexpression significantly inhibits MHV-68 viral replication, while PCBP1 knockdown enhances viral replication. Studies of PCBP1 activity show an inhibition of late viral promoter but not early promoter, suggesting that PCBP1 regulates viral replication during the late stage of lytic replication. Claire seeks to characterize how the protein-protein interaction between cellular poly(C) binding protein 1 and viral ORF 34 regulates viral late gene expression and affects viral replication.
Claire would like to thank Dr. Ren Sun, Shaoying Lee, and all members of the Sun lab for their wonderful mentorship and the incredible opportunity to conduct research as an undergraduate. Research has greatly enriched her undergraduate education. She is also very thankful for the Helga K. and Walter Oppenheimer Scholarship and the Undergraduate Research Scholars Program. Claire will attend medical school after graduation. She hopes to obtain a dual MD/MPH degree and pursue academic medicine.
| Mr. Charles Seller
Mr. Charles Seller
Mentor: Dr. Andrew Diener
Funding: Ehrisman Scholar
Title: The Functional Significance of Supernumerary Chromosomes in the Plant Pathogen Fusarium Oxysporum
Charles is a fourth year majoring in MCD Biology. He has been working in Dr. Andrew Diener's Plant Pathology lab since his third year. The lab's focus is on studying the host-pathogen relationship between the plant pathogen, and emerging human pathogen, Fusarium oxysporum and its host plant.
The plant pathogen Fusarium oxysporum (Fox) is the cause of a devastating wilt disease afflicting a number of agriculturally important crops, such as banana, tomato, and cotton. Genomic comparisons of several Fusarium species have shown that pathogenic races of Fox contain several conditionally dispensable, or supernumerary, chromosomes. Supernumerary chromosomes contain genes that are not required for normal growth, but may contribute a selective advantage under certain conditions, like while infecting a plant.
Charles's current project will test the hypothesis that the supernumerary chromosomes in Fox play a role in virulence. He will design a protocol to select for Fox mutants that have lost a part of or their entire supernumerary chromosome. These mutants can then be used in an infection assay in Arabidopsis thaliana to determine if they have lost any virulence. This project will demonstrate the functional significance of supernumerary chromosomes in Fox, and help locate the actual genes that contribute to virulence.
After graduating Charles hopes to attend medical school. He would like to express his sincere thanks to Dr. Diener for his patience and guidance, and to the entire Diener lab for their aid in his project. Charles would also like to thank the donors to the Ehrisman fund for their generous support, and the URC/CARE office for giving him this opportunity.
| Ms. Marissa Sneddon
Ms. Marissa Sneddon
Mentor: Dr. Joseph Watson
Funding: Sparks Scholar
Title: The nature of human α-synuclein protein in a mouse model for Parkinson's Disease
Marissa Sneddon is a fourth year undergraduate student majoring in Neuroscience and minoring in Southeast Asian Studies. She has been conducting research in Dr. Watson's lab since the middle of her second year at UCLA. Now under Dr. Watson's guidance, she is studying the α-synuclein protein in brain mitochondria of a transgenic mouse model for Parkinson's Disease (PD). Parkinson's disease is associated with the accumulation and over-expression of α-synuclein protein in the brain, as well as mitochondrial dysfunction.
It has recently been shown that α-synuclein is found in low levels in normal mitochondria, but preferentially accumulates in the mitochondria of the substantia nigra and striatum of PD brain and can impair mitochondrial Complex I of the electron transport chai n . This may contribute to mitochondrial dysfunction such as oxidative stress and play a role in the pathogenesis of PD. In her research project, Marissa will determine the nature of human α-synuclein (soluble, non-soluble, aggregated, cleaved?) elevated in PD mitochondria.
Marissa would like to thank Dr. Watson for his help and guidance, as well as the other members in her lab for their enthusiasm and assistance . She is also deeply appreciative of the Jones family and URC/CARE for all their support. Marissa will graduate UCLA in the spring of 2010 and plans on applying to medical school.
| Ms. Hoang-Lan Tran
Ms. Hoang-Lan Tran
Mentor: Dr. Katherin Plath
Funding: Van Trees Scholar
Title: A proteomic approach to understanding the mechanism of X-inactivation
Hoang-Lan Tran is a fourth year Biochemistry Major and Biomedical Research Minor currently working in Dr. Kathrin Plath's lab in the Department of Biological Chemistry at the David Geffen School of Medicine.
Under the mentorship of Ryan Schmidt, Hoang-Lan studies a phenomena known as X-inactivation. In mammals, dosage compensation between the sexes is monitored by the silencing of one of a female's two X chromosomes. This X-inactivation process is mediated by Xist, a 17 kb noncoding RNA that spreads across the target chromosome to initiate and maintain gene silencing.
In 2002, Anton Wutz, (one of Kathrin's colleagues in the Jaenisch lab,)showed that a highly conserved repeat sequence located at the 5' end of Xist, dubbed "A", is crucial to the actual gene silencing function of the RNA. Deletion of the A repeats resulted in Xist that is capable of coating the target chromosome but unable to induce gene silencing, while mutations within the repeat region produced varying levels of loss of function. Interestingly enough, the repeat sequence is predicted to fold into two stem loops, forming a structure that may serve as a scaffold for binding protein factors. Using genetic and biochemical techniques, Hoang-Lan hopes to identify these possible factors to explore the silencing mechanism of Xist.
Hoang-Lan would like to thank Dr. Kathrin Plath and Ryan Schmidt for their patience and mentorship, all the members of the Plath lab for their support, as well as Mrs. Knapp for her generous contribution to the Van Trees Scholarship.
| Ms. Lillian Tran
Ms. Lillian Tran
Mentor: Dr. Jeffrey H. Miller
Funding: Sparks Scholar
Title: Methods to Examine the Novel Antibiotic Bicyclomycin, an Inhibitor of the Termination Factor, Rho
Lillian Tran is a fourth year Microbiology, Immunology, and Molecular Genetics major who has conducted research in the bacterial genetics lab of Dr. Jeffrey H. Miller since spring quarter of her sophomore year. Under his guidance, she has extensively studied and profiled a unique antibiotic bicyclomycin through multiple experimental methods, especially the use of single gene deletion Escherichia coli mutants.
Bicyclomycin (BCM) represents a unique class of antibiotics which primarily functions by inhibiting the transcription termination factor, Rho. Therefore, BCM causes cells to produce long transcripts and, in Escherichia coli, causes cells to express cryptic prophage genes, some of which induce lethality. However, by testing the Keio collection containing close to 4000 single-gene knockouts of Escherichia coli against several subinhibitory concentrations of BCM, we discovered around sixty genes that, when deleted, caused increased susceptibility to BCM. These results show that BCM affects many different targets in the cell which may or may not be a downstream effect of Rho inhibition. This study also looks at a biochemical approach to characterizing and potentiating BCM through the determination of synergistic effects between BCM and other antibiotics. This will be accomplished by combining subinhibitory concentrations of BCM and another antibiotic into liquid cultures of a wild-type E. coli strain. The discovery of syngeristic effects between BCM and another antibiotic helps to clarify how BCM interacts with other chemicals and will prove to be highly beneficial in combinatorial drug therapy. Combined, these results provided insight on the mechanisms of bicyclomycin and prove that it affects more structures and pathways than just transcription inhibition. The experimental model developed here, which includes synergistic experiments and the use of single gene deletion E. coli mutants, can be propagated and used to study the mechanisms of any novel and unique antibiotic.
Lillian would like to thank Dr. Jeffrey H. Miller for his continuing mentorship and support along with the other members in his lab. She would also like to thank URC/CARE and Mr. Sparks for their generosity in supporting her research. Lillian is currently applying to medical school and hopes to specialize in infectious diseases.
| Mr. Dinh Truong
Mr. Dinh Truong
Mentor: Dr. Mohamed Abdou
Funding: Van Trees Scholar
Title: Experimental Measurement of Lithium Ceramic Pebble Bed Deformation at Prototypical Fusion Blanket Conditions
Dinh Truong is a fifth-year Mechanical Engineering undergraduate. He has been an undergraduate researcher in the Fusion Science & Technology Center since June 2007. Dinh's research interest lies in the area of magnetic confinement fusion energy technology, ranging from plasma confinement to material science. His current research project deals with experimentally characterizing the steady state deformation of lithium ceramic pebble beds at high temperature and stress.
For fusion energy to be viable, fusion reactors must be able to produce and maintain a sufficient inventory of tritium. A proposed method of "breeding" tritium is through a reaction between the neutrons produced by fusion and lithium, in which the products are tritium and helium. A concept under consideration for breeding tritium is a helium-cooled pebble bed "blanket", where the reactor walls are lined with lithium ceramic pebbles. These breeding blankets must operate under extreme conditions of several Mega-Pascals and up to 900°C. In order to develop the necessary predictive tools and set design limits for breeding blankets, the thermo-mechanics state of lithium ceramic pebble beds must be quantified at relevant operating conditions. Dinh's project will study the deformation, stress and temperature gradient relations for lithium ceramic pebble beds to understand the mechanism for pebble bed failure so that it can be avoided.
Dinh is grateful for the support and encouragement of his family. He would also like to thank Prof. Abdou, Dr. Alice Ying, and the members of the Fusion Science & Technology Center for their guidance.
| Mr. Aria Vazirnia
Mr. Aria Vazirnia
Mentor: Dr. Robert Moldin
Funding: Ehrisman Scholar
Title: The Role of Micronutrients in the Innate Immune Response
Aria Vazirnia is currently a fourth year psychobiology major at UCLA working in the immunology laboratory of Dr. Robert Modlin, specifically under the guidance of post-doctoral fellow, Dr. Philip Liu. He joined the lab in June 2007 and for the past two years has been elucidating the way with which vitamin D enhances our immune system to combat Mycobacterium tuberculosis.
Monocytes express receptors called Toll-like 2/1 receptors (TLR2/1) which become activated once binding to a specific 19kD mycobacterial lipopeptide. Activation of these receptors causes the induction of the hydroxylase enzyme cyp27b1 as well as the upregulation of the Vitamin D Receptor (VDR). Cyp27b1 converts the inactive vitamin D3 (25D3) prohormone to its active form (1,25D3). The 1,25D3 binds to VDR and this complex works as a transcription factor to upregulate genes encoding antimicrobial peptides, such as cathelicidin.
As part of the 2009-2010 URSP program, Aria is investigating the differential efficacies of vitamin D2 (ergocalciferol) vitamin D3 (cholecalciferol) in combating Mycobacterium tuberculosis. Given that vitamin D deficiency is reaching global pandemic levels in people, Aria believes that the results of this study have much clinical relevance.
After graduation, Aria will be attending medical school and hopes to become a leading figure in translational medicine. As an undergraduate researcher at UCLA, Aria has been very grateful for the mentorship and support he has received from both Dr. Robert Modlin and Dr. Philip Liu. In addition, Aria extends his thanks and utmost appreciation to the Thomas A. and Virginia Ehrisman Scholarship Fund and URC/CARE for supporting his research interests.
| Mr. Daniel Vu
Mr. Daniel Vu
Mentor: Dr. Sophie Deng
Funding: Oppenheimer Scholar
Title: Determination of Homeodomain only Protein as a Marker for Corneal Epithelial Stem Cells
Daniel Vu is a third year Biochemistry undergraduate student at UCLA. At the UCLA Jules Stein Eye Institute, Daniel is in his second year at Dr. Sophie Deng, MD/PhD's cell biology lab, which studies corneal epithelial stem cells and their capacity to repair the damaged cornea through tissue engineering. The aim of his research is to determine whether HOP (homeodomain only protein) gene expression is a potential marker for corneal epithelial stem cells (CESCs).
Corneal Epithelial Stem Cells (CESCs) have been determined to lie in the basal layer of the limbus and are the precursor cells of the corneal epithelium. Since there are currently no well-established markers to locate and identify CESCs in the limbus, the defining properties of this stem cell niche are still undetermined. From the lab's microarray data, gene expression profiling showed that nine new genes including HOP exhibited higher expression levels in the limbus than in the cornea, and therefore are possible markers for CESCs. Daniel is currently analyzing the gene expression patterns of HOP and other potential markers for CESCs in the limbus and cornea to determine whether HOP expression can be used to characterize stem cell identity. Daniel will also determine whether cultured limbal cells express this potential marker for CESCs, which will further elucidate the defining properties of CESCs and their niche . This work will advance the long-term goal of tissue engineering and transplantation.
Daniel is thankful for his lab training and for the opportunity to learn from both Dr. Deng and postdoctoral fellow Thuy Truong, PhD. Currently, Daniel's career research interests center around the improvement of treatments and therapies in medicine.
| Ms. Allison Wong
Ms. Allison Wong
Mentor: Dr. Paula Diaconescu
Funding: Hilton Scholar
Title: Differential Ligand Effects on Lanthanide Reactivity towards N-heterocycles
Allison Wong is a 3rd year Biochemistry student at UCLA. Currently, she works in the Chemistry department in the group of Dr. Paula Diaconescu studying organometallic complexes. More specifically, she is interested in the reactivity of group III metal complexes towards aromatic nitrogenous heterocycles, which has implications for the purification of fuels.
Prior studies have found few organometallic catalysts which can cleave the C-N bonds of N-heterocycles. The Diaconescu group (UCLA) has described the ring opening of a substituted imidazole molecule by a scandium alkyl complex supported by a silylated ferrocene ligand, and is currently investigating the ring opening reactions of more chemically robust and industrially significant pyridines. Allison is investigating the reactivity of analogous lutetium alkyl complexes supported by alternatively substituted amidoferrocene ligands with substituted pyridines. By varying the supporting ligand, she influences the reactivity of the metal alkyl complex by steric and electron donating effects. These reactions have significance for the industrial breakdown and removal of pyridine rings from bitumen and oil shale, as present catalysts are both expensive and environmentally unsound. The discovery of homogeneous organometallic catalysts which cleave C-N bonds could enable cleaner, greener processes and help elucidate unexplored reactivity of group III metals.
Allison is especially grateful to Dr. Diaconescu for her guidance, as well as to the URC/CARE staff for their assistance and for the many opportunities made available through this office.
| Mr. Daniel Wu
Mr. Daniel Wu
Mentor: Dr. Genhong Cheng
Funding: Ehrisman Scholar
Title: Transcriptional regulation of Toll Like Receptor induced Interleukin 10
Daniel Wu is a fourth-year Physiological Science major. He began researching in Dr. Genhong Cheng's laboratory in January 2009. Daniel conducts research on immune response regulation with the guidance of Shankar Iyer, a graduate student. The focus of his research is to understand the regulation of interleukin-10 (IL-10), a cytokine produced by macrophages that has been widely described as playing a role in regulating inflammation within the body. The dysregulation of IL-10 has been implicated in the development of several autoimmune diseases: multiple sclerosis, rheumatoid arthritis, and psoriasis.
Macrophages represent an important source of IL-10, yet the mechanisms regulating IL-10 production are poorly understood. The Cheng laboratory and others have demonstrated that Toll-Like Receptor (TLR) signaling in macrophages leads to IL-10 production. The goal of Daniel's research is to elucidate the molecular mechanisms responsible for TLR mediated induction of IL-10. Preliminary data from his work and others in the Cheng lab have demonstrated that IL-10 production via TLR signaling involves the production Type I Interferons and the anti-inflammatory agent interleukin 27, both of which also play important roles in regulating autoimmune disease. Ultimately, Daniel's work will uncover important factors implicated in the regulation of IL-10 gene expression in macrophages.
Daniel plans on attending medical school after completing his undergraduate studies at UCLA. He would like to thank the URC program, Mr. Lewis, and the Thomas A. and Virginia Ehrisman Fund for their generosity and for their support of his undergraduate research. He would also like to thank Dr. Genhong Cheng and Shankar Iyer for their support and guidance.
| Ms. Paula Wu
Ms. Paula Wu
Mentor: Dr. Ronald Harper
Funding: Oppenheimer Scholar
Title: Differential responses of anterior insular cortex subregions to the Valsalva Maneuver
Paula is a Neuroscience major with a concentration in Biomedical Research. She is also a Howard Hughes Undergraduate Research fellow, the Managing Editor of Reviews of the HHMI-funded UCLA Undergraduate Science Journal, and a co-chair of the startup journal of the Neuroscience Undergraduate Society. She plans to pursue a joint MD/PhD degree upon graduation.
For the past two years, Paula has worked in the lab of Dr. Ronald Harper in the department of Neurobiology. Paula is currently examining the participation of discrete insular cortex subregions in cardiovascular control. The insular cortex shows a somatotopic organization for visceral processing, but localization of other integrative processes is unclear. Using fMRI, she is studying the neural recruitment of insula gyri during the Valsalva Maneuver, a standard autonomic task. A previous project examined the altered neural responses in the insular cortex in Sleep Apnea patients.
Paula is also involved in an ongoing collaboration with the Section on Functional Imaging Methods in the Laboratory of Brain and Cognition at the National Institutes of Health under the direction of Dr. Peter Bandettini. As a summer intern at the NIH, she studied the global fMRI Blood Oxygenation Level Dependent signal response to the Valsalva Maneuver. B reath holding has emerged as a useful technique for understanding BOLD contrast and for calibrating the fMRI signal, and the Valsalva is a common breathing challenge similar to the breath hold. Understanding the BOLD response to the Valsalva could aid in potentially developing a novel fMRI calibration method, and help to further elucidate how the contribution of cerebral hemodynamic and intracranial pressure changes during the Valsalva affect the BOLD signal.
Paula is indebted to the URC-CARE, Oppenheimer fund, Howard Hughes Undergraduate Research Program, Harper lab, Bandettini lab, and the support of her family and faith.
| Ms. Lei Xu
Ms. Lei Xu
Mentor: Dr. Joan Valentine
Funding: Sparks Scholar
Title: Investigations into the cause of the increased mitochondrial content of sod1Δ yeast
Lei Xu is a fourth year student majoring in Molecular, Cell, and Developmental Biology. She is currently applying to medical school. She joined the Valentine lab in fall of 2007 and has been a member ever since. During her first year in the lab, she was mentored by Dr. Clement, and since fall of 2008 she has been researching independently. Currently she is investigating the cause of the increased mitochondrial content, a mutant phenotype, of CuZnSOD deficient yeast.
The ability to utilize dioxygen in generating ATP has made it an essential molecule to nearly all multicellular organisms. Dioxygen however, is also toxic to the cell as the natural byproducts of its metabolism, reactive oxygen species (ROS), can cause oxidative damage to DNA, lipids, and proteins. In particular, superoxide anion is a precursor for many of the ROS. Dr. Valentine's lab studies superoxide stress and superoxide dismutase (SOD), an antioxidant enzyme which catalyzes the dismutation reaction of superoxide anion. Almost all higher organisms contain some form of SOD; the model organism S. cerevisiae (Baker's yeast) contains CuZnSOD (SOD1) and MnSOD (SOD2). Sod1Δ yeast exhibit many mutant phenotypes, most of which are not well understood. Recently, Dr. Valentine's lab has discovered that sod1Δ yeast have increased mitochondrial mass and oxygen consumption compared to wild-type when grown under aerobic conditions on glucose. Lei is currently investigating the possible contributing factors to the increased mitochondrial content of sod1Δ yeast. Through the use of beta-galactosidase reporter assays she has shown that sod1Δ yeast grown on glucose have a higher induction of CYC1 (cytochrome c) than wild-type and that this is the result of upregulated Hap2p/3p/4p/5p activity. The Hap2p/3p/4p/5p complex is a transcription factor known to regulate many genes involved in mitochondrial biogenesis and it plays an important role in glucose derepression. Her current working hypothesis is that sod1Δ yeast are not able to undergo full glucose repression and as a result they respire more than wild-type.
Lei would like to thank Prof. Valentine, Dr. Edith Gralla, Jake Martins, and the rest of the Valentine Lab for their continued support and encouragement. They have provided a nurturing and intellectually stimulating environment for the past 2 years and inspired her to continue to do research as a part of her future career. She would also like to thank Mr. Jones for his kindness and generosity in supporting her research
| Ms. Gabriela Kuftinec
Ms. Gabriela Kuftinec
Mentor: Dr. Donald Kohn
Funding: Hilton Scholar
Title: Use of lentiviral vector to correct Sickle Cell Anemia
Gabriela is currently a fourth year student majoring in Microbiology, Immunology and Molecular Genetics with a minor in Italian. She began working is Dr. Donald Kohn's lab in the Spring of 2009. Under the guidance of Dr. Kohn as well as post-doctoral student, Satiro De Oliveira , Gabriela has been studying the possibility of using stem cells and gene therapy to correct the Sickle cell anemia mutation in patients with the disease.
Sickle cell disease results from a single amino acid change in a person's hemoglobin b chain molecule. One current treatment against the disease is to inject into an infected patient the bone marrow of a healthy individual, which often results in immune rejection by the recipient patient. Gabriela's projects is to take the bone marrow from a sickle cell patient, and to insert into the stem cells a vector with a normal b chain hemoglobin chain gene, and put the bone marrow back into the patient it came from. The patient's bone marrow could then, hopefully, make normal red blood cells itself, and there would be no problems of immune rejection because the bone marrow came from the patient own body.
Gabriela is extremely grateful to Dr. Kohn, Satiro and the entire Kohn lab for the valuable mentorship and support she has received throughout her time in the lab. She would also like to thank Diane and Henry Hilton and URC/CARE for their generous financial support.
| Ms. Wai Yin (Rona) Law
Ms. Wai Yin (Rona) Law
Mentor: Dr. Steve Jacobsen
Funding: Van Trees Scholar
Rona Law is a fourth-year undergraduate student majoring in Molecular, Cell, and Developmental Biology at UCLA. She has been conducting research under the supervision of Dr. Steve Jacobsen and Dr. Angelique Deleris since her third year in the department of Molecular, Cell and Developmental Biology.
Studying and comparing the functions of histone demethylases, which mediate epigenetic modifications at the histone level give us more insight in DNA methylation mechanisms. Her project involves identifying proteins in the Arabidopsis thaliana, particularly Jumonji (JMJ) histone demethylase genes, which are paralogs of crucial mammalian developmental genes. She is studying the roles of putative histone demethylase J5, where the j5 mutant displays an earlier flowering time compared to a wild-type Columbia (col) plant. Current studies involve characterizing the roles of the jmj-C domain containing histone demethylases. Her long term goal is to confirm whether or not the inactivation of one Jumonji histone demethylase gene via phenotype and genotype, leads to the genetic redundancy of another j5 gene, both of which are from the same family of histone demethylases.
Rona plans on pursuing a career in medicine after she graduates from UCLA. She would like to thank Dr. Angelique Deleris and Dr. Steve Jacobsen for their continuous support and guidance, Mrs. Knapp and the Van Trees Estate for their generosity and financial support, and the Undergraduate Research Center for the incredible opportunity.
| Mr. Tyler Lee
Mr. Tyler Lee
Mentor: Dr. Dean Buonomano
Funding: Wasserman Scholar
Title: Exploring Cortical Responses to Speech Stimuli using Neural Network Simulations
Tyler Lee is a fourth year Neuroscience major and Mathematics minor. He plans to attend graduate school in Neuroscience next year and ultimately to pursue a faculty position in the same field. He has worked under Dr. Dean Buonomano since Spring 2007. Tyler is utilizing neural network simulations to investigate cortical speech processing.
By simulating neural responses to speech stimuli, Tyler hopes to elucidate how the cerebral cortex discriminates distinct speech stimuli. Language is a superbly complex phenomenon that is, in its syntactically complex forms, a uniquely human capability. The goal is to investigate how higher level cortical areas are able discriminate different spoken words in a time-dependent manner. Personal experience tells us that hearing a word spoken in reverse, even though it stimulates identical frequency bands, is unlikely to be mistaken for the word itself. Computationally, however, the discrimination of forward and reverse stimuli is very difficult. A properly tuned recurrent neural network should be capable of creating enough temporal asymmetry in the neural responses to allow for this discrimination. Tyler is investigating how the tuning parameters of the recurrent network affect the ability to discriminate the stimulus that evoked a given response.
Tyler would like to thank the Wasserman family for funding his research, the URC for their support of him throughout his undergraduate career, and Dr. Dean Buonomano for his support and guidance.
| Mr. Alan Lewis
Mr. Alan Lewis
Mentor: Dr. Terri Hogue
Funding: Miller Scholar
Title: Hydrological Modeling of the Arroyo/Simi Basin in the Calleguas Creek Watershed Using the Hydrologic Simulation Program FORTRAN (HSPF)
Alan Lewis is a fifth-year Civil and Environmental Engineering major at UCLA who is specializing in water. This year he began conducting research in the Department of Water Resources Engineering and Hydrology under the guidance of Dr. Terri Hogue and Dr. Janet Barco.
Dr. Hogues lab focuses on improving the understanding of hydrologic fluxes at a range of space and time scales. With a special focus on semi-arid regions, she and her dedicated group graduate students have been working to develop and improve tools to better understand the mechanisms and improve the prediction of hydrologic processes.
Alan is currently working to model the upper Arroyo Simi portion of the Calleguas Creek watershed in Southern California using the Hydrologic Simulation Program FORTRAN (HSPF), developed by the United States Environmental Protection Agency (USEPA). Computer models are capable of providing holistic interpretations of the complex natural hydrologic processes that drive watershed behavior and how they impacted by anthropogenic disturbances. HSPF processes input estimates of potential evapotranspiration and precipitation data using hundreds of process algorithms derived from theory, laboratory experiments, and empirical relations from instrumented watershed. Alans project mainly utilizes such algorithms as interception soil moisture, surface runoff, interflow, base flow, evapotranspiration, temperature, and land cover to compute streamflow hydrographs. The goals of his research are to successfully calibrate and validate the model and to perform a sensitivity analysis.
Alan will be graduating from UCLA in the Spring and hopes to attend graduate school in environmental fluid mechanics and hydrology beginning in Fall 2010. He would like to extend his sincere gratitude to Dr. Hogue, Dr. Barco, and their research team for their guidance and inspiration during his academic pursuits. He also would like to thank the Miller Foundation and URC/CARE for their generosity as he prepares for the next step in his education.
| Ms. Anqi Li
Ms. Anqi Li
Mentor: Dr. Ina Wanner
Funding: Boyer Scholar
Title: Mechanosensor Stimulation of STAT3 Pathway via GSK3β Activation in Reactive Astrogliosis
Anqi is currently a fourth year Neuroscience student. She has been working in Dr. Ina Wanner's lab since Fall 2007. Under the guidance of Dr. Wanner, she has learned a lot in the field of glia, in particular reactive astrogliosis, which is not often covered in undergraduate courses.
Astrocytes are the "body guards" of the brain and crucial in providing nutrients and maintaining the integrity of the neuronal networks in the CNS. When a traumatic impact injures the nervous tissue, astrocyte are activated and accumulate around the lesion site in a process called astrogliosis. Its benefit lies in its prevention of further spread of inflammation. However, astrogliosis is also detrimental because it may inhibit axonal regeneration. Dr. Wanner's lab is interested in studying the mechanisms of astrocyte activation after mechanical trauma. Currently, Anqi is studying the role of a signaling enzyme called glycogen-synthase kinase 3β in STAT-mediated astrocyte activation.
Thanks to the mentorship and support of Dr. Ina Wanner, Anqi has been able to pursue her passion for research in the neuroscience. She has also acquired experience in conducting and analyzing experiments on cell death and proliferation of traumatized astrocytes. She would also like to thank the Boyer Family for their generous support in helping her pursue her passion for science.
| Ms. Jinxin (Stephy) Li
Ms. Jinxin (Stephy) Li
Mentor: Dr. Richard Kaner
Funding: Boyer Scholar
Title: Fabrication of Freestanding Films of Polyaniline Nanofibers
Stephy Li is with the departmental scholars program in the chemistry/biochemistry department, hoping to obtain her B.S. and M.S. at the same time when she graduates next year. She has been conducting research in the Kaner lab since January 2008 and has participated in various projects since. Stephy is currently working on making freestanding thin films of conducting polymers, especially polyaniline (PANI).
Conventional conducting polymers are already being used and/or examined for many applications, for instance, batteries, sensors, actuators, catalysts, and electromagnetic shielding and so on. Stephy has been carrying out synthesis of PANI nanofibers and making thin films of this material on hydrophilic substrates. The focus of her upcoming project is to develop an easy method for the fabrication of freestanding films of polyaniline nanofibers. Organic conductors will be synthesized via non-assisted polymerization as well as initiator-assisted polymerization. The doping levels and the morphology of the nanofibers are then controlled to afford thin homogeneous films of nanofibers on substrates such as quartz, borosilicate and soda lime glass. The films are characterized using scanning electron microscopy, UV-vis spectroscopy and electrochemical tools such as cyclic voltammetry.
She hopes that one day the Kaner group can be able to gather enough information for creating a handbook, in which the morphologies and characteristics of PANI nanofibers synthesized under different conditions will be listed, so people can choose the one suited for them to use for research and industrial purposes.
Stephy is planning on pursuing a career in medicine after graduating from UCLA. She would like to thank Dr. Kaner, Julio D'Arcy, as well as the rest of the Kaner group for their gracious guidance, encouragement, and support. She would also like to extend her sincere gratitude to URC/CARE for the opportunity and the Boyer Family for their generous endowment.
| Mr. Benjamin Liu
Mr. Benjamin Liu
Mentor: Dr. Steve Jacobsen
Funding: Oppenheimer Scholar
Title: Elucidating the H3K27me1 gene silencing pathway
Benjamin Liu is a fourth year Bioengineering major. This is his second year working in Dr. Steve Jacobsen's lab under graduate student Hume Stroud. His main focus is on the monomethyltransferase proteins ATXR5 and ATXR6.
In Arabidopsis Thaliana, epigenetic marks such as DNA-methylation and histone modification play a vital role in gene regulation. One well-established gene-silencing pathway involves both DNA-methylation in CHG-context and histone modification: the removal of either CHG DNA-methylation or H3K9me2 (Histone 3 Lysine 9 di-methylation) leads to transcriptional activation of transposable and repeat elements. Unlike the well-understood gene silencing pathway through the epigenetic mark H3K9me2, many questions remain with H3K27me1 (H3K27 mono-methylation). What we do know is that the proteins ATXR5 and ATXR6 (ATXR5/6) have H3K27 monomethyltransferase activity. We need to identify whether the ATXR5/6 enzymes are in the same pathway as various other enzymes. To do this we are creating triple mutants of ATXR5/6 with each of these enzymes of interest and then comparing levels of gene reactivation with methods such as RT-qPCR. Then we will test to see how ATXR5/6 interacts with the CHG-methylation pathway.
Benjamin would like to express his sincere gratitude to Hume Stroud, Dr. Steve Jacobsen, and all the rest of the marvelous people at Jacobsen Lab for their constant guidance and also the Helga K. and Walter Oppenheimer Scholarship fund for their generous support.
| Ms. Shirley Liu
Ms. Shirley Liu
Mentor: Dr. Irvin Chen
Funding: Oppenheimer Scholar
Title: Optimization of hematopoietic stem/progenitor cell differentiation from human embryonic stem cells and human induced pluripotent stem cells
Shirley is a third year Biology major. She has been working in Dr. Irvin Chen's laboratory in the department of Microbiology, Immunology, and Molecular Genetics since her freshman year. Under the guidance of Dr. Masakazu Kamata, Shirley is working on increasing the efficiency of hematopoietic differentiation from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC).
Hematopoietic stem/progenitor cells (HSPC) are of major interest for diverse clinical applications, ranging from leukemia treatment to AIDS therapy. HSPC can be isolated from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC), providing a potentially unlimited source of cells as well as eliminating immunologic rejection and preventing disease transmission from donors. A standing problem, however, is the extremely low efficiency of HSPC differentiation from hESC and hiPSC. Efficient differentiation is essential for clinical translation, but spontaneous generation of HSPC from hESC and hiPSC results in few and heterogeneous cell populations. Shirley has been optimizing HSPC differentiation from hESC and hiPSC, testing different media conditions (OP9 stromal cell coculture and embryoid body formation in the presence or absence of various hematopoietic cytokines). She is also working on developing a fluorescent protein assay system for HSPCs based on lineage-specific expression of microRNAs, as well as determining if expression levels are correlated with pluripotency and differentiation potentials.
Shirley would like to thank Dr. Irvin Chen for the opportunity to conduct research in the lab, and Dr. Masakazu Kamata and Dr. Koki Morizono for their guidance and support. She is also very grateful for the generosity of the Oppenheimer fund and URC/CARE.