Cellular and Molecular Medicine
University of California, San Diego
9500 Gilman Drive
La Jolla, CA 92093-0651
1994 Searle Scholar
My lab is interested in Cell and Molecular Biology of splicing. At the biochemical level, our effort is devoted to understand the mechanisms of pre-mRNA splicing in mammals, especially how splice site is selected. Because cell growth and differentiation are associated with numerous alternative splicing events, and deregulation of splicing has been attributed to cancer in an increasing number of cases, we pay special attention to the regulation of alternative splicing. We are currently using Biochemical and Cell Biology techniques to identify key enzymes and factors in the regulation, to analyze their roles cell structure and function, and to explore their regulation by intracellular and external signals. Specifically, the research projects in the lab include:
- Regulation of HIV tat pre-mRNA splicing by the splicing factor ASF/SF2. Based on our published data, ASF/SF2 is the only splicing factors tested that efficiently commits HIV tat pre-mRNAto the splicing pathway. Using this model system, we are addressing the RNA element(s) in tat pre-mRNA and the protein element(s) in ASF/SF2, that are required for the specific activation of splicing by this protein, but not by other structurally and functionally related splicing factors.
- Regulation of a splicing-specific kinase and its role in constitutive and regulated splicing. We have recently identified and cloned a novel cell cycle regulated kinase named SRPK1. This kinase is highly specific for splicing factors involved in splicing and splice site selection. This molecule provides an opportunities for the first time in the splicing field to study how signal is trandused to regulate splicing.
- Nuclear structure and organization of splicing machinery. Because splicing is an important nuclear function and splicing factors are compartmentalized in the nucleus, we are interested in the spatial relationship among gene expression events from transcription, to RNA processing, and to mRNA transport. These studies may provide molecular bases for structural changes in the nucleus during cell growth and differentiation
- Cell- and tissue-specific alternative splicing. We are interested in search for factors that determine cell- and tissue-specific splicing. We are using the in situ hybridization technique to determine the expression pattern of the SR family of splicing factors, and plan to apply mouse knockout technology to address the function of these splicing factors in animal development.