The Undergraduate
Research & Teaching
Scholars Program
2007-2008
Ms. Preethika Ekanayake
Ms. Kyeong Kim
Mr. Edward Pham
Mr. Andy Tran
Mr. Michael Zhang
Ms. Anne Zhujiang
Ms. Preethika Ekanayake
Mentor: Dr. Barney Schlinger
Funding: Wasserman Scholar
Title: Sex differences in the activity levels of 17-beta hydroxysteroid dehydrogenase enzyme type 4 in the Zebra Finch Brain
Dr. Barney Schlinger and Preethika Ekanayake
Preethika tutoring
Preethika Ekanayake is a fourth year Neuroscience student at UCLA. When she moved to California eight years ago from Sri Lanka, she never dreamt about attending UCLA or working side by side with some of the greatest scientific minds in the nation. Since she had very little knowledge of the language, the transition was difficult at first. Nonetheless, she adapted, and succeeded in becoming the first person from her family to attain a college education. She is now on her third year of research at the Neuroendocrinology laboratory of Dr. Barney Schlinger.
Steroid hormones are fundamental modulators of sexual behavior and sexual differentiation of neural structures. The zebra finch song system is an excellent example of a sexual dimorphism that is determined by the actions of steroid hormones. Zebra finch males sing a previously learned song during courtship, whereas females do not sing. This dimorphism is expressed in the structures of the song system, including the nuclei responsible for learning and motor performance of song such as HVC and RA, with the nuclei in the male larger than the same nuclei in the female brain. It is known that the brain is capable of de novo steroidogenesis. Therefore, differences in mRNA expression levels and specific activity levels of enzymes that are responsible for the interconversion between different types of steroid hormones might explain the observed sexual dimorphism in the zebra finch brain and behavior. Preethika’s project will look at one such ubiquitous class of enzymes.
The steroidogenic enzyme class of 17 b Hydroxysteroid Dehydrogenases (17 b-HSD) catalyzes the last key step in the steroidogenic pathway. The type four isozyme primarily carries out the oxidative reaction that converts 17 b-Estradiol (E2) to Estrone (E1). Preethika’s project will examine the specific activity levels of this 17 b-HSD type 4 enzyme in the zebra finch brain to determine whether there exists a sex difference in the activity levels of this enzyme between male and female brains. Previous studies done in the Schlinger lab have shown that the expression level of type 4 enzyme is higher in males (ZZ) than in females (ZW). In situ hybridizations and Northern Blot analysis have shown that males have twice the amount mRNA of this enzyme as females. Moreover, from studies conducted in the Arnold lab, we know that the gene that encodes for this enzyme resides on the Z chromosome. Therefore Preethika’s experiments will complement the previous studies by analyzing the specific activity levels of this particular enzyme in the zebra finch brain, which will determine if differences in mRNA expression are translated into differences in protein levels.
Preethika would like to thank her mentor, Dr. Barney Schlinger and all the other members of the laboratory for their continuous support and guidance. Moreover, she would like to extend her gratitude to the Wasserman family for their generosity and encouragement of her research, and to UCLA URC/CARE center for their support and kindness.
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Ms. Kyeong Kim
Mentor: Dr. Ren Sun
Funding: Hilton Scholar
Title: Creating a herpesviral vector for cancer therapy using Murine Gamma Herpesvirus-68
Dr. Ren Sun, Kyeong Seon Kim, and Dr. Seungmin Hwang
Kyeong Seon Kim with her tutees for Life Science 15. From the left: Linda, Millie, Kyeong Seon, Jessica, and Lindsey
Kyeong Seon Kim is a fourth year student majoring in Physiological Science. After receiving B.S. in Spring 2008, she plans to take off a year and work as a lab technician. Then she plans on continuing her studies. She has been working in Sun Lab, under the guidance of Dr. Ren Sun and Dr. Seungmin Hwang, since Summer 2006. Her current research concentrates on creating a viral vector for the clearance of prostate cancer.
Prostate cancer is the second leading cause of cancer death for men in the United States. Recently, the studies have shown that the expression of immune costimulatory LIGHT gene in tumor cells induced an increase in recruitment and activation of tumor-specific T cells, which led to the clearance of the tumor. However, LIGHT gene must be expressed constitutively within the host for clearance of the tumor. Viral vectors are used for gene expression, but the vectors being employed at the moment have many faults. Some integrate into the host’s DNA which imposes a threat of oncogenic cancer development. Others are incapable of being expressed and proliferated constitutively in the host. In Sun Lab, Murine Gamma Herpesvirus-68 is being characterized. We believe that Murine Gamma Herpesvirus-68 would be an ideal vector because it can stay as a stable episome without integrating into the host’s genome and because it can replicate stably as the host cells go through mitosis. It has a large coding capacity, ideal for carrying LIGHT gene. Novel viral vectors using Murine Gamma Herpesvirus-68 will be created through big deletions of the viral genome: one for gene delivery and another for packaging. The goal of this project is to modify Murine Gamma Herpesvirus-68 so that it can deliver and express LIGHT gene stably and tissue-specifically. Then the viral vector expressing LIGHT gene will be tested for its ability to lead to the clearance of prostate cancer.
Currently, Kyeong Seon is a tutor for Life Science 15 at the Advanced Academic Placement Program. She enjoys working with some of the brightest students at UCLA, and she would like to thank her tutees for giving her a chance to teach as well as to learn from them.
Kyeong Seon would like to thank Dr. Sun and
Dr. Hwang for the guidance and encouragement.
She would also like to thank Ms. Ann Porteus
of Hilton Estate and Dr. Cramer for the support.
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Mr. Edward Pham
Mentor: Dr. Daniel T. Kamei
Funding: Wasserman Scholar
Title: Inhibition of transferrin iron release increases in vitro drug carrier efficacy
Edward Pham and Dr. Daniel T. Kamei
Edward tutoring in Chemistry 20A and 20B, AAP
Edward Pham is a fourth year Bioengineering student. He has conducted research in the laboratory of Dr. Daniel T. Kamei in the department of Bioengineering since spring quarter of his freshman year. Besides research, Ed also serves as a Vietnamese interpreter at the UCLA Medical Center. He is also involves in other campus organizations such as the Vietnamese Language and Culture, the Biomedical Engineering Society, and Tau Beta Pi. He has also been a chemistry and physics tutor for Covel Commons. Currently, he is the Chemistry 20A and 20B tutor at the Academic Advancement Program.
Ed’s research project aims to develop transferrin as a carrier molecule for antineoplastic agents. One of the major problems in the current treatment of cancer is the presence of highly toxic side effects associated with chemotherapeutics. It is therefore desirable to selectively target cytotoxins to cancerous cells while minimizing their effects on normal cells. Transferrin (Tf), a serum iron-transport protein, is a promising drug delivery vehicle, since its receptor (TfR1) is overexpressed on cancer cells. This overexpression exists because the physiological function of Tf is to deliver iron from the bloodstream into cells, and cancerous cells require more iron to sustain their abnormal growth. Accordingly, cytotoxins may be preferentially delivered to cancerous cells by conjugating them to Tf. Although researchers have been investigating this approach for several years, the rapid recycling behavior of Tf limits its efficacy. Specifically, Tf is present in the cell for only about 10 minutes, and the cytotoxin must be released inside the cell in this short time period
To improve the efficacy of Tf as a drug carrier, Ed’s research group has sought to increase its cellular association, and therefore, increase the probability for delivering cytotoxins to the cells. To achieve this goal, a whole cell kinetic model was derived using the principles of mass-action kinetics to identify molecular parameters that could be altered to increase Tf cellular association. This is a forward engineering approach where a systems analysis of cellular processes is used to identify novel design criteria. Our model predicted that slowing down the iron release rate of Tf inside the cell could increase its cellular association, which could, in turn, increase its efficacy as a drug carrier. Although ligand/receptor interactions have been altered for several years in the field of drug delivery, to the best of our knowledge, this was the first attempt at altering a ligand/metal interaction for the purpose of drug delivery.
A Tf variant with an inhibited iron release rate was generated by varying the synergistic anion, and as predicted these Tf variants showed a higher degree of cellular association. Importantly, diphtheria toxin (DT) conjugates of this Tf variant are about 4-fold more cytotoxic against HeLa cells than conjugates of native Tf. Tf variant can also be generated using site-directed mutagenesis with an even slower iron release rate. With these new variants, Ed will conjugate them to DT and subsequently purify and characterize them. He will also perform cell culture and the MTT assay to determine IC 50 values for new conjugates being generated
Ed would like to express his utmost gratitude to Dr. Kamei for giving him the opportunity to conduct research. Since day one, Dr. Kamei has always been a patient, supportive, and inspiring mentor. Ed would also like to thank all the lab members for always fostering a family-like environment. He also wants to thank the Wasserman family for their generosity and their commitment to make a difference in lives of those they have not even met. Ed plans to attend medical school upon his graduation. As a Vietnamese immigrant, Ed hopes that his success will serve to inspire other immigrants as well.
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Mr. Andy Tran
Mentor: Dr. Sherie Morrison
Funding: Wasserman Scholar
Title: Characterization of Fc gamma 1 receptor binding specificity to human and mouse IgG subclasses
Andy Tran is a third year Microbiology, Immunology, and Molecular Genetics. His research interests lie primarily in biological science, most particularly in the field of cellular immunology. Andy will be tutoring Statistics 13 at the Advanced Academic Placement Program. Aside from his ongoing research, Andy is also devoted and involved in the Student Committee on Ethic and Honors; Premed-Asian Pacific American Medical Student Association; and Health C.A.R.E. (a collaborative mobile clinic).
Under the supervision and guidance of Dr. Sherie Morrison, Andy will be characterizing the binding specificity of FcγR1 (CD64). In particular, he is most interested in studying the pathogenesis of Cryptococcus neoformans and Cryptococcus gattii which are basidiomycetous fungi (polysaccharide encapsulated yeast-like fungi) that cause life-threatening infections in immunocompetent as well as immunocompromised hosts (e.g. people infected with HIV). However, the uses of antibody-mediated immunity to the capsule polysaccharide glucuronoxylomannan (GXM) of C. neoformans may lead to a favorable host defense. Moreover, antibody-mediated Fc receptors play an integral role in the protective functions of the immune response against the infection, whereas FcγR1 is a high affinity receptor that binds to the Fc region of IgG Isotypes and is important for inducing phagocytosis and opsonization through the activation of the complement pathways. Ultimately by comparing and contrasting the FcγR1 binding specificity to human and mouse IgG Isotypes specific for C. neoformans and C. gattii, Andy hopes to shed further light into the pathogenesis of the infectious pathogens.
In order to purify FcγR1 and, subsequently, examine its specificity, Andy will be making recombinant FcγR1 genes through bacterial transformation; purifying bacterial plasmids through Maxiprep; and transiently transfecting 293T cells to produce soluble, cell-free FcγR1. FcγR1 will be removed from serum through affinity chromatography by using Sepharose columns coupled with IgG; then, the concentrated eluate will be assayed using ELISA on Microtiter Plate couples with fluorescent fusion proteins against the monoclonal antibody isotypes. These assays will characterize the binding specificity of high affinity FcγR1 and further analysis will be made to reach the research’s objectives.
Andy would like to express his gratitude to Dr. Morrison for giving him the opportunity to broaden and expand his research experiences as well as the members of her lab for their continual support and wholehearted encouragement. Andy would also like to thank Dr. Audrey Cramer and the Undergraduate Research Center for inspiring his passion for science as well as the Mr. and Mrs. Wasserman for their generosity and looking out for student researchers. Through these fulfilling experiences, Andy plans on joining an MD/Ph.D program with the ambition of becoming a medical scientist devoted to biomedical research. Andy’s Dream is to one day be able to pay back the perpetual sacrifices his parents have made to ensure his success and happiness as a family of immigrants in the United States.
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Mr. Michael Zhang
Mentor: Dr. Thomas Vondriska
Funding: Alcott Scholar
Title: Investigation of Tec tyrosine kinase signaling in ischemic myocardium
Dr. Thomas Vondriska and Michael Zhang
Michael tutoring in Biochemistry, at AAP
Michael is a fourth year Microbiology, Immunology and Molecular Genetics student. He has been performing research in Dr. Vondriska’s laboratory since 2006. His research interests are in the signal transduction activities of Tec protein tyrosine kinases in the ischemic heart. Tec kinases are known to be activated by growth stimuli in cell proliferation and survival. Michael’s recent data shows Tec expression change following ischemic injury to the heart. Therefore it is hypothesized that the role of Tec in the heart is to transducer extracellular signals to intracellular targets via phosphorylation to regular cell survival. Michael is employing classical biochemical methods coupled with mass spectrometry to investigate this hypothesis.
Prior to working with Dr. Vondriska, Michael was privileged to have gathered invaluable experience in the laboratory of Dr. Peipei Ping studying membrane proteins, and in Drs. Kym Faull and Julian Whitelegge’s laboratory learning liquid chromatography and mass spectrometry techniques. Building upon past experience and under influence of Dr. Vondriska’s enthusiastic guidance, Michael plans to finish a complete research project upon graduation in June 2008.
In addition, Michael is also tutoring Biochemistry 153L for AAP. The subject material in the class is directly related to Michael’s research and as such allows him to impart valuable experience to his students. This is Michael’s first official tutoring job, but as he is naturally inclined towards didactic rambling, he finds his job very enjoyable.
Michael is extremely grateful of Dr. Vondriska’s patient and persistent mentorship without which he would not be able to integrate past lab experiences and focus on a defined research project. He would also like to thank everyone in the Vondriska Lab for their help and support, Dr. Peipei Ping for providing his first research position, members of the Ping Lab for fostering his research capabilities, and Drs. Kym Faull and Julian Whitelegge for introducing him to the most important tool in spectroscopy, the mass spectrometer. Finally, Michael would like to thank Dr. Audrey Cramer and the URSTP committee for their confidence in his research and the Rosalind Alcott Estate for their generous funding.
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Ms. Anne Zhujiang
Mentor: Dr. James Waschek
Funding: Hilton Scholar
Title: Pituitary adenylate cyclase activating polypeptide and sonic hedgehog interaction in the developing cerebellum
(from left to right): Dr. Niewiadomski, Annie Zhujiang, and Dr. Waschek
Annie tutoring in the AAP Math/Science lab
Annie is a fourth year studying neuroscience and economics. Under the guidance of Dr. Niewiadomski in Dr. Waschek's laboratory, she is currently investigating the interaction between pituitary adenylate cyclase activating polypeptide (PACAP) and sonic hedgehog (SHH) in the developing cerebellum. On cultured cerebellar granule precursor cells, SHH increases proliferation of the cells. Its action is returned to nearly basal levels when SHH treated cells are also exposed to PACAP. PACAP seems to cause the inhibition of SHH action through the PKA pathway, as PKA inhibitor H89 blocks the effects of PACAP on HH-pathway induced gene expression. However, PKA inhibitor H89 alone increases HH-pathway activation by PACAP and by other pathway related factors. Additional evidence present suggests that multiple pools of PKA are in the cell, with different pools being activated in each case. Further studies will attempt localize the potential groups of PKA, with the primary cilium being a highly possible location. PACAP, SHH, and the interaction between them are likely to play a role in CNS development, thus elucidating the precise mechanism of the PACAP-mediated inhibition of SHH-promoted cell proliferation and understanding their roles are important in gaining insight into normal cerebellar development and medulloblastoma formation.
In addition to spending time in Dr. Waschek's laboratory, Annie enjoys tutoring in the AAP Math/Science lab. Annie feels privileged to be a part of the program and loves the chance to work with such gifted and fascinating students. She would like to thank Emmanuel Owaka and the rest of the AAP staff for allowing her to be a part of the AAP family, as well as her previous and present Chemistry 153A and 14D students for many fun memories. She would also like to express her gratitude to Dr. Niewiadomski and Dr. Waschek for their patience, guidance, and giving her the opportunity to participate in such an interesting project. Finally, she would like to thank Dr. Audrey Cramer, the Undergraduate Research Center, and the Hilton Scholarship Foundation for supporting her passions.
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