William W. Mattox, Ph.D.
1987, California Institute of Technology
The University of Texas M. D. Anderson Cancer Center
Department of Genetics
|
William W. Mattox, Ph.D. 1987, California Institute of Technology The University of Texas M. D. Anderson Cancer Center |
Research Interests:
Our lab studies the alternative splicing of pre-mRNAs. This is an important mechanism by which an individual gene can produce distinct proteins in different cells. The mechanism is surprisingly common and it is now estimated that transcripts from more than 60% of all human genes undergo some form of alternative processing. In the beautiful fruitfly Drosophila, alternative splicing plays a central role in sex determination. We have been using the sex-determination system to study factors that influence alternative splicing and to determine the mechanisms by which they do so. Several of the proteins we are studying belong to the serine/arginine-rich (SR) family of splicing factors. These proteins usually bind to sequences located within exons, known as exonic splicing enhancers (ESEs) and activate nearby splice sites. We have found that an SR factors can repress splicing when bound within an intron. Using in vitro splicing assays and Drosophila genetics we are determining how splicing activation and repression differ.
A second interest of the lab is in genetic models for muscular dystrophy. Recently we have developed a transgenic Drosophila model for facioscapulohumeral muscular dystrophy (FSHD) a poorly understood late-onset disease that affects specific muscle groups in humans. We are using genetic approaches to identify genes that reverse the muscle defects in these flies as a way to understand the molecular basis of the disease.
Selected Publications:
Lazareva AA, Roman G, Mattox W, Hardin PE, Dauwalder B (2007) A role for the adult fat body in Drosophila male courtship behavior. PLoS Genetics 3:115-122.
Qi J, Su S, Mattox W (2007) The doublesex splicing enhancer components Tra2 and Rbp1 also repress splicing through an intronic silencer. Molecular and Cellular Biology 27:699-708.
Qi J, Su S, McGuffin ME, Mattox W (2006) Concentration dependent selection of targets by an SR splicing regulator results in tissue specific RNA processing. Nucleic Acids Research 34:6256-6263.
Xu DQ, Mattox W (2006) Identification of a splicing enhancer in MLH1 using COMPARE a new assay for determination of relative splicing efficiencies. Hum Mol Genet 15: 329-336.
Program Affiliations:
Program in Cell and Regulatory Biology Reproductive Biology Track