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The Undergraduate Research
Scholars Program2007-2008
Mr. Eric Sarkissian
Mr. Navneet Sharma
Mr. Geoffrey Smith
Mr. Andrew Su
Ms. Jingwen Tan
Mr. Joseph Thouin
Mr. Kasey Topp
Ms. Quynh-Minh Tran
Ms. Jiu Yi Tsai
Mr. Gary Tse
Ms. Wendy Tseng
Mr. Jonathan Wang
Ms. Yimeng Xia
Ms. Yin Zhen
Ms. Maggie Zhu
Mr. Eric Sarkissian
Mentor: Dr. Karen Lyons
Funding: Boyer Scholar
Title: Investigating the Roles of CCN1 and CCN2 in Cartilage
Eric Sarkissian is a fourth year undergraduate majoring in Physiological Science. He plans to pursue a career in medicine after graduation. Eric has been performing research in Dr. Karen Lyons' laboratory for two years under the guidance of postdoctoral fellow Andrea DeYoung. The focus of the lab is to study the role of the CCN family of matricellular molecules in vertebrate development. These proteins are known to play crucial roles in skeletal development, but their specific roles in cartilage maintenance and development are unknown.
This project is designed to examine the roles of two of these molecules, CCN1 and CCN2, in cartilage maintenance. In the lab, specific strains of mice have been generated that lack Ccn1 and/or Ccn2 specifically in the cartilage. Initially, skeletal formation will be examined using whole-mount skeletal preparations to assess the severity of the defects in the different strains in comparison to a control group of wild-type littermates. Then, serial tissue sections of skeletal elements from these different genotypes will be made to view the effects of the loss of CCN1 and/or CCN2 on cellular organization and morphology by using a set of histological techniques and immunohistochemistry with antibodies for the cartilage-specific extracellular matrix proteins. Immunohistochemistry will also be used to examine the levels and activation states of proteins in the TGF b and integrin signaling pathways, as these are both known to be important for CCN function. Based upon these data, the roles of CCN1 and CCN2 in specific aspects of cartilage formation, differentiation, and maintenance in the growth plate will be characterized.
Eric would like to thank Dr. Lyons, Andrea, as well as all members of the lab for their constant help and support. He also expresses his gratitude to the Boyer Estate for their generous donation.
Mr. Navneet Sharma
Mentor:
Funding: Van Trees Scholar
Title:Profile/Picture coming soon!
Mr. Geoffrey Smith
Mentor: Dr. Michael Teitell
Funding: Sparks Scholar
Title: The Characterization of PNPase, TCL1, and Their Interactions in Mitochondria
Geoffrey Smith is a fourth year physiological science major. He is beginning his second year of research in the Michael Teitell laboratory. The laboratory focuses on mechanisms of cancer formation and progression. There is a special emphasis on studies of leukemia and lymphoma that arise during normal B cell development. More specifically the Teitell lab is involved in determining the primary roles of T cell leukemia-1 (TCL1), a gene that is involved with causing lymphoma and leukemia. Recent data has indicated that the TCL1 oncoprotein, or cancer causing protein, interacts with a mitochondrial protein polynucleotide phosphorylase (PNPase).
PNPase supports respiration and maintains mitochondria homeostasis with an unknown role in affecting fusion versus fission, regulates energy metabolism, and controls cell proliferation. PNPase is a potential candidate to promote cancer via the interaction with TCL1. Geoffrey’s current project involves isolating mitochondria to better characterize the role of TCL1, PNPase, and their interactions. These isolated mitochondria will also be used to test for interactions that PNPase has with other proteins to better understand its function. The ultimate goal is to determine PNPase’s effect on TCL1 and its role in oncogenesis.
After graduating from UCLA, Geoffrey plans to take a year off before applying to medical school. He will continue researching in Dr. Teitell’s laboratory during the time. Geoffrey would like to thank Dr. Michael Teitell and everyone else in the Teitell laboratory. He would also like to graciously thank his donors for their support.
Mr. Andrew Su
Mentor: Dr. Osvaldo Rey
Funding: Wasserman Scholar
Title: Characterization of Structure-Function of G-protein Calcium-Sensing Receptor Agonist Binding Domains
Andrew Su is a fourth-year Biochemistry major at UCLA. He spends his days conducting research under the guidance of Dr. Osvaldo Rey in the Department of Medicine—Division of Digestive Diseases in Warren Hall where he will study the human G-protein Calcium-Sensing Receptor (CaR).
Concentrations of intracellular free calcium ([Ca 2+] i) play a key role in a variety of biological processes including cell proliferation and differentiation, hormone and neurotransmitter secretion, cell motility and apoptosis. CaR is an allosteric protein receptor which can affect [Ca 2+] i levels through its ability to bind to two different agonists, extracellular Ca 2+ ([Ca 2+] e) and aromatic amino acids. While the two agonists both bind to CaR, the [Ca 2+] i oscillations stimulated by each differ considerably in amplitude, frequency, and duration.
Andrew will be working to help determine the location and mechanism of interaction between CaR and its two agonists. Through site-directed mutagenesis in select domains of the CaR, he hopes to help define which regions of the CaR respond to which agonist. Successfully created mutants will then be stably transfected into human embryonic kidney cells (HEK 293) to observe their affects on [Ca 2+] i in vitro.
Upon graduating, Andrew plans to take a one year hiatus before pursuing his career aspirations in medical school. However he understands that good medicine only comes from good research. Thus he would like to take this time to show his appreciation to everyone who has made his undergraduate research experience such a rewarding one. Mainly he would like to thank Dr. Osvaldo Rey and Romeo Papazyan for sharing their knowledge and time with him. He would also like to thank the Wasserman Family for their generous donation and support of his undergraduate research at UCLA.
Ms. Jingwen Tan
Mentor:
Title:
Mr. Joey L. Thouin
Mentor: Dr. Jeffrey Kraut
Funding: Bonner Scholar
Title: Effect of acute metabolic acidosis on gene expression in the rat heart
Joey Thouin is a fourth year undergraduate student majoring in Physiological Science. Since fall 2006, he has conducted research under the guidance and supervision of Dr. Jeffrey Kraut, in the UCLA - VHAGLA Membrane Biology Laboratories of Dr. George Sachs. Joey is completing his honors thesis on the effects of induced metabolic acidosis on cardiac gene expression and protein abundance in ventricular tissue of an established rat model.
Clinically, metabolic acidosis contributes to a loss of organ function, particularly the heart in which decreased pH levels lead to cardiac output and contractility problems, arrhythmias, and hypoxia. However, the exact causal relationship between organ malfunction and pH remains unclear. Additionally, the traditional treatments for acidosis have not had a positive effect on cardiac function. To identify the factors involved in that causal relationship, Joey will continue studying the effects of acidosis, trying to deduce cellular pathways regulated or altered by low pH environments. He is completing experiments across various time exposures to 1.5M NH 4Cl acid treatment. The study will then utilize both microarray analysis to expose gene expression changes, using quantitative PCR for verification of affected gene classes, as well as proteomic studies to elucidate protein trends from 2D differential gel electrophoresis. For further analysis, Joey will compare his results with other derivations of acidosis (LPS-induced sepsis, hypovolemic shock, etc.), in efforts to isolate a causal factor of acidotic symptoms and therefore a target for effective therapy.
After graduating from UCLA this spring, Joey plans to attend medical school. He would like to thank Dr. Kraut, Elisabeth Berger, and everyone in the Sachs lab for their continued guidance and support. Joey also extends his sincere gratitude to Bonner for their generosity and advocacy of student research at UCLA.
Mr. Kasey Topp
Mentor: Dr. Christina Jamieson
Funding: Bonner Scholar
Title: Role of Dysferlin in Apoptosis
Kasey is a fourth year Microbiology, Immunology and Molecular Genetics student. She has plans to attend Grad school and hopes to one day apply her research to help solve environmental issues. She has been working under the guidance of Dr. Jamieson since January of 2006. Currently she is studying the gene dysferlin which is associated with the genetic disorder dysferlinopathy. Dysferlinopathy is a crippling disorder marked by the loss of skeletal muscle tissue.
Kasey is using in vitro models to study the role of dysferlin in muscle cell apoptosis and muscle development. Her lab collaborates with another lab to collect multipotent mesenchymal stromal cells from wild-type and dys -/- mice. Using myogenic media the cells are driven to differentiate into muscle cells. By inducing apoptosis with tert-butylhydroperoxide (oxidative stress) she is able to study the morphological features of apoptosis. The TUNEL assay is used to measure apoptosis. Also, she uses dexamethasone to study dys-/- muscle cells’ ability to induce apoptosis in mygogenesis. Kasey hopes that once the role of dysferlin in apoptosis is better understood it will be easier to find effective treatments for dysferlinopathy.
Her second project is to design an experimental model to screen selective androgern receptor modulators (SARMs) for positive effects on muscle differentiation of dys -/- stromal cells incubated in myogenic media. Then once she has obtained possible therapeutic SARMs for dysferlinopathy patients, she plans to design experiments to determine any harmful side effects the SARMs may have on other tissues.
Ms. Quynh-Minh Tran
Mentor: Dr. Utpal Banerjee
Funding: Bonner Scholar
Title: Second hit genes that interact with AML1-ETO in Drosophila melanogster to induce acute myeloid leukemia
Quynh-Minh Tran is currently a fourth year Molecular, Cell, Developmental Biology major. Since Fall 2006, she has been working under the direction of Dr. Utpal Banerjee, Dr. Sergey Sinenko, Dr. Ira Clark, and Dr. John Olson, on a genetic screen in Drosophila melanogaster in order to elucidate the other genes that, when mutated in the presence of AML1-ETO, are responsible for the onset of acute myeloid leukemia.
The AML1-ETO fusion protein has been implicated in 5%-21% of all acute myeloid leukemias. AML1-ETO acts as a constitutive repressor at the normal AML1 binding site and represses the transcription of the AML1 gene. AML1-ETO is a fusion protein composed of the AML1 homologous binding sites and a major portion of the ETO protein. Previous research indicates that AML1-ETO alone will not induce leukemia; however, leukemia was prevalent in mutagenized cells that contained this fusion protein. This led to the theory that a second hit was required for the disease to manifest. From this data, this project is in the process of conducting a genetic screen for genes that potentially interact with the fusion protein to cause the onset of acute myeloid leukemia. Further research on the interaction of these genes with AML1-ETO will give insight into the cause and perhaps the prevention of this cancer.
Minh would like to thank Mr. Christopher Montgomery for this opportunity, as well as the Undergraduate Research Consortium in Function Genomics (URCFG) research program , her mentors, lab mates, and family for their ongoing support.
Ms. Jiu Yi Tsai
Mentor: Dr. Jochen Stutz
Funding: Miller Scholar
Title: Retrieval of vertical concentration profiles of urban air pollutants
Tsai Jui Yi (Catalina) is a fifth year undergraduate student majoring in Chemistry. Her concern about air quality led her to conduct atmospheric chemistry research under the guidance of Dr. Jochen Stutz in the department of Atmospheric and Oceanic Sciences. Her research is focused on the observational study of urban pollutants. Little information on trace gas levels in the altitude range of 100 to 1000 meters is currently available, thus limiting our ability to validate air quality models, which are essential to the development of air pollution mitigation strategies. The derivation of vertical concentration profiles of pollutants in the lowest 1000 meters of the atmosphere is thus highly desirable and is the specific focus of Catalina’s research.
Catalina has been part of Dr. Stutz’s group since winter of 2007. She is currently working on the retrieval of NO 2, O 4, HCHO and HONO concentrations and profiles from observations in Mexico City. The data was collected using the Multi-Axis Differential Optical Absorption Spectroscopy technique, which measures scattered sunlight at multiple viewing elevations. The spectral analysis of the specific absorptions yields path-averaged concentrations of these gases. Vertical profiles are then retrieved by combining the observations with radiative transfer model calculations. The techniques developed in this project will offer a fully automated method to retrieve vertical distributions of pollutants. The derived profiles will help to evaluate and improve air quality models for Mexico City.
Catalina would like to thank Dr. Stutz and his group for giving her support and guidance. She would also like to extend her gratitude towards the Undergraduate Research Scholar Program and her donors for helping her achieve her academic goals.
Mr. Gary Tse
Mentor: Dr. James Waschek
Funding: Sparks Scholar
Title: Patterning Analysis of Transcription Factors in Developing Neural Tube of PACAP Deficient Mice
Gary Tse is a fourth year Neuroscience major at UCLA and has been conducting research under the supervision of Principle Investigator James Waschek. He has been working for the past year and a half with PACAP (pituitary adenylyl cyclase activating peptide), a neuropeptide that has been shown to be involved in enumerative neurophysiological events such as controlling expression of different genes and as a signaling molecule. PACAP and its high-affinity receptor PAC1 are widely expressed in the developing mouse neural tube. Their lab previously showed that PACAP increases cAMP levels while decreasing cellular proliferation and gene expression of gli-1, a target gene of Shh in cultures of embryonic hindbrain neural progenitors. Therefore it has been suggested that PACAP is early inducer of cAMP levels in the embryo and may act in the neural tube during pattering to control cell proliferation and gene expression in vivo. Gary hypothesizes here that PACAP acts in the neural tube during early embryonic stages to affect neural patterning and neurogenesis, impart by antagonizing the patterning action of Shh. He proposes to use the knockout mice model in conjunction with immunohistochemical and in situ hybridization analysis to research the relationship between PACAP, Shh, and cellular proliferation. The study of spinal cord development and its early neural patterning is pertinent to the knowledge about the spinal cord as well as understanding the development of diseases that occur in the spinal cord. Their studies of PACAP’s early role in affecting cellular proliferation and neural patterning can contribute to the wealth of knowledge and research that is pertinent for creating relevant therapies. Gary would like to thank Dr. Waschek for his continual guidance, and expresses gratitude to the Hales Sparks Estate for their support for student research at UCLA.
Ms. Wendy Tseng
Mentor: Dr. Yin Tintut
Funding: Bonner Scholar
Title: Transcriptional Regulation of Interleukin-6 by Oxidized Phospholipids
Wendy Tseng is a third-year student majoring in Physiological Sciences. She has been conducting research under the guidance of Dr. Yin Tintut in the Division of Cardiology, David Geffen School of Medicine since 2005.
Her ongoing research focuses on the oxidized phospholipids regulation of interleukin-6 (IL-6) expression by osteoblasts, bone-forming cells. IL-6 is one of the cytokines involved in stimulating differentiation of osteoclasts, bone-resorbing cells. Previously Dr. Tintut and colleagues have shown that oxidized phospholipids, which trigger pathogenesis of atherosclerosis, also regulate bone cells differentiation and maturation. Investigating mechanisms of IL-6 expression will provide a better understanding of the regulatory role of atherogenic phospholipids in bone cells. In addition,
the findings may shed light on the prevalence of osteoporosis in patients with cardiovascular disease.
By quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), Wendy has found that oxidized phospholipids induce IL-6 expression in preosteoblast calvarial cell line, MC3T3-E1, and that the induction is mediated by extracellular signal-regulated kinase. She is
currently extending her findings by investigating transcriptional regulation of murine IL-6 promoter-reporter constructs by oxidized phospholipids.Wendy is grateful for the opportunities and guidance provided by Dr. Tintut and the support from her fellow colleagues. She especially thanks Bonner for its generous financial support and the Undergraduate Research Center for an excellent research opportunity as she plans to pursue a joint MD/PhD program in the near future.
Mr. Jonathan Wang
Mentor: Dr. Jennifer Jay
Funding: Miller Scholar
Title: Bioremediation of Sediment
(Dr. Jennifer Jay and Jonathan Wang)
Jonathan Wang is a fourth year Civil & Environmental Engineering major under the mentorship of Professor Jennifer Jay. It was only three years ago when he first entered UCLA with hopes of becoming a civil & environmental engineer. Now, three years later, he is well on his way to achieving his academic dream.
He is currently researching the effect of pH on the autotrophic process during denitrification based sediment remediation. He will be observing how pH affects organisms in sediments while less nitrogen is provided; this will allow him to determine how to treat certain types of pollution most effectively and costly.
The nitrate-enhanced bioremediation of sediment, as a cost-effective in situ treatment process, has increasingly received much concern and interest. However most studies carried out so far in bioremediation have underestimated the role of autotrophic process. Some chemolithotrophic microorganisms can utilize reduced sulfur compounds, measured as acid volatile sulfide (AVS), in sediments as electron donors for anoxic respiration. This process potentially may affect nitrate-enhanced bioremediation in two aspects: (1) The reduced sulfur compounds in sediments may compete with target organic contaminants for nitrate as electron accepter; and (2) the consumption of sulfide alters the speciation of heavy metals in sediment resulting in increasing toxicity or leaching of heavy metals.
Environmental factors may affect the competition between autotrophic and heterotrophic process during nitrate-enhanced bioremediation. The study of these effects will be helpful for both understanding mechanism, and engineering optimization.
In this study the effect of pH on denitrification in sediment will be examined in batch experiment. Both GC and IC will be used to monitor the process of denitrification. Since sulfate is generated only in autotrophic process. By comparing the sulfate generation and nitrate consumption at different pH, the effect of pH on the competition between autotrophic and heterotrophic process will be unveiled.
Providing a cleaner and safer environment has always been a lifetime goal and will not only benefit UCLA, but the world. After graduation, Jonathan plans to pursue a PhD in Environmental Engineering and eventually develop his own Civil and Environmental Engineering company.
Ms. Catherine Xia
Mentor: Dr. Yibin Wang
Funding: Bonner Scholar
Title: The role of PP2Cm in the development of obesity, diabetes, and cardiovascular disease
Catherine Xia is currently a fourth year undergraduate student majoring in physiological sciences. She feels very fortunate to be able to return for a second year as a student researcher within Dr. Yibin Wang’s lab in the Department of Anesthesiology. Dr. Wang’s lab has discovered a novel protein phosphatase (PP2Cm) that plays a critical role to mitochondria function, ROS production and cellular survival. In order to investigate the physiological function of PP2Cm in intact animal, a mouse model with genetic inactivation of PP2Cm is created. Catherine will participate in the genotypic and phenotypic characterization of this novel PP2Cm null mutant mouse model using an array of molecular and physiological tools. Catherine will prepare genomic DNA from the tissue and use PCR to determine the genotype of the animals whether they carry the PP2Cm null alleles. Subsequently, she will maintain a cohort of age, gender matched mutant and wildtype animals to measure their cardiovascular function by serial echocardiography analysis, their total, lean, fat and water body weights by using an NMR detection system, and finally monitor their plasma insulin/glucose levels at basal and following acute glucose infusion. She will perform these studies following the natural development of these animals from 2 months to 12 months of age, under normal or high-fat diet. These studies will provide important insights to the functional role of PP2Cm in normal development, energy metabolism and potential contribution to disease conditions such as heart failure, obesity and diabetes.
Ms. Sally (Yin) Zhen
Mentor: Dr. Barney Schlinger
Funding: Bonner Scholar
Title: The Effect of Steroid Hormones in Regulating Neurogenesis in the Ventricular Zone of the Adult Avian Brain
Sally (Yin) Zhen is a fourth year student double majoring in Psychobiology and Neuroscience. She is currently conducting her research study in the laboratory of Dr. Barney Schlinger in the Department of Physiological Science. Sally is investigating the effects of steroid hormones on cellular proliferation in the zebra finch brain. The role of steroid hormones as regulators of reproductive processes has been extensively studied. However, their function in the central nervous system has not been fully understood. These sex steroids stimulate brain differentiation in males and females (sexual dimorphism) as well as influence sex-specific behaviors. Certain steroid hormones are synthesized directly in the brain, suggesting a function in the central nervous system. Sally will investigate the effect of different sex hormones in cultured brain cells. She will label newly-born cells and compare the degree of neurogenesis in the ventricular zone between control groups and hormone-treated groups.
Sally will be graduating in Spring 2008 and plans on continuing research in the future with the eventual goal of attending medical school. She would like to thank Bonner for its generous support as well as Dr. Schlinger, Dr. Amnon Katz, and the rest of the Schlinger lab for their guidance. She would also like to express her gratitude to the Undergraduate Research Center for extending this exciting opportunity.
Ms. Xiaoming (Maggie) Zhu
Mentor: Dr. Eric Vilain
Title: Wnt4 signal mediated by β-catenin in developing mammalian ovaries
Xiaoming (Maggie) Zhu is a senior majoring in Molecular, Cell and Developmental Biology. She is working in Dr. Eric Vilain’s laboratory in the department of Human Genetics. The research of the Vilain laboratory focuses on the molecular basis of sex determination in mammals. Maggie is currently studying Wnt4, a signaling molecule involved in female sex determination.
In early fetal development, gonad is morphologically indistinguishable in male and female. In male, the expression of Sry directs gonad to follow the testicular pathway. In female, Wnt4 is involved in the ovarian pathway; however, the molecular mechanism of Wnt4 action is unknown in this context. Previous experiments showed that cell migration from the mesonephros into the developing gonad, a critical feature of testicular development, is repressed by Wnt4. In cell culture, Wnt4 re-localizes β-catenin, a cell adhesion molecule, to the cell membrane and cell-cell expression adhesion is increased. As adhesion prevents cell migration, Maggie hypothesized that Wnt4 re-localizes β-catenin to the cell membrane in the developing ovary to inhibit male-like cell migration. To test this hypothesis, Maggie will perform immunohistochemistry to localize β-catenin in both wild type (WT) and Wnt4 knock-out (KO) mouse embryonic gonads. She expects to see β-catenin localizing with cell-cell adhesion markers on the cell membrane in WT ovaries, but not in WT testes or Wnt4 KO ovaries. Maggie’s project will contribute to the establishment of molecular mechanism of mammalian female sex determination, and it will ultimately help the rapid diagnosis and management of atypical genital formation
