18. GOALSFORFELLOWSHIPTRAININGANDCAREER The goal of this fellowship and of my graduate school career is to obtain a Ph.D. from the University of California, Irvine. Under this fellowship, I intend to develop critical thinking skills that will allow me to analyze my own data as well as the findings of others. Also, in addition to learning molecular genetics and biochemical techniques that will provide me with the tools to design my own experiments, I hope to acquire good writing and verbal skills so that I can present my research to the scientific community in a clear and concise manner via publications and oral presentations. All of these tools are important and will be useful for performing independent research after graduate school, such as in a post-doctoral setting. My ultimate career goal is to become a professor at a research university or conduct research at a biotechnology company. My main interests lie in cancer, regulation of gene expression, and in signal transduction pathways, and after graduate school, I intend to continue conducting research in this field. / -']if,.] _I,.'_.i] lg. NAME AND DEGREE(S) Marian L. Waterman, Ph.D. 20. POSITION/RANK Associate Professor in Department of Microbiology and Molecular Genetics, UCI College of Medicine 21. RESEARCH INTERESTS/AREAS The molecular basis of Cancer il:l'__'-_:['1;llIK']:_'_'/-', 22. DESCRIPTION(Donotexceedspaceprovided) Mutations that cause aberrant activation of the Wnt Signaling Pathway are found in early stages of tumor development in colon carcinoma. The downstream components of the pathway are transcription factors that belong to the LEFFFCF family, and the focus of our lab is to study the regulation of the LEF1 gene. Northern blot analysis demonstrates that there are 3 LEF1 messages (3.6kb, 3.0kb, and 2.2kb) expressed from the locus. Two different promoters generate the 3.6 and 2.2 kb mRNA messages and have been characterized. The promoter for the 3.6kb message is a target of the Wnt pathway and is aberrantly expressed in colon cancer cell lines. The 3.0kb message is also aberrantly expressed in cancer, but its origin is not known. The focus of this proposal is to test the hypothesis that a region in exon 1 of the LEF1 gene harbors a third promoter which directs expression of the third LEF1 message (3.0kb) (Aim 1). Because the 3.6 and 3.0 kb messages are expressed together in colon cancer cell lines, we hypothesize that they are coordinately regulated. Due to the identification of a region in promoters 1 and 3 in exon 1 that contains putative Wnt and TGF_-response elements, experiments will be carried out to test if these elements individually play a role in the regulation of one or both promoters (Aim 2). If this putative regulatory region affects promoter activity, we plan to determine whether the Wnt and TGF_ pathways cooperate to activate or act antagonistically to negatively regulate promoter 1 and 3 (Aim 3). Mutations in the TGFI3 Pathway are late events in the development of tumorigenesis, therefore, we hypothesize that the aberrant expression of LEF1 in colon carcinomas may be due to mutations that activate the Wnt pathway and mutations that inactivate the TGF_ pathway. PHS 416-1 (Rev. 12/98) Form Page 2 BB CC Individual NRSA Application NAME (Last, first, middle initial) Table of Contents ========================================Section End===========================================
| Tsai, Becky Pinjou; Jimenez, Judith; Lim, Sharon et al. (2014) A novel Bcr-Abl-mTOR-eIF4A axis regulates IRES-mediated translation of LEF-1. Open Biol 4:140180 |
| Jimenez, Judith; Jang, Gwendolyn M; Semler, Bert L et al. (2005) An internal ribosome entry site mediates translation of lymphoid enhancer factor-1. RNA 11:1385-99 |
