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William W. Mattox, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Research Interests

  • Alternate RNA splicing
  • Sex determination
  • Animal models for disease

My lab has two distinct interests. One focus is on the mechanisms by which cells regulate RNA processing. Genome studies have revealed that many complex organisms have fewer genes than expected. One explanation for this lies in the fact that genes often generate alternative mRNAs and thus encode multiple distinct proteins. To produce alternative mRNAs, exons must be combined in different patterns during RNA splicing in a carefully controlled way. The choice of exon sequences that are picked is regulated by both splicing activator and repressor proteins which bind pre-mRNAs and act locally to either favor or block recognition of nearby splice sites by the spliceosome. We have found that splicing repression can be carried out by some of the same proteins that cause activation. These proteins interact with each other to form similar complexes, but ultimately have opposite effects on the RNA. By investigating how these complexes interact with the pre-mRNA splicing machinery we are gaining insight into the mechanisms of splicing regulation.

A second major interest of my lab is in the development of the reproductive system. In most animals, gonads arise separately from other reproductive ducts and organs, but must fuse with them to form a continuous reproductive tract. In Drosophila we have found that fusion of the testis with the reproductive tract depends on the morphogenesis of an epithelial layer at the posterior tip of the testis. The mechanism by which this occurs is almost entirely unknown but we have found that proteins from the DM family of transcription factors play a required role. Interestingly, the DM proteins are among the only factors known to have a conserved role in sexual differentiation across the animal kingdom. We are investigating the function of these factors using genetic and molecular approaches with the goal of understanding signals that direct differentiation of the reproductive tract and coordinate organ fusion.

Office Address

The University of Texas M. D. Anderson Cancer Center
Department of Molecular Genetics, Unit 1006
1515 Holcombe Blvd.
Houston, TX 77030
Room Number: S11.8136B
Phone: 713-834-6329
Email: wmattox@mdanderson.org

Education & Training

Degree-Granting Education

1986 California Institute of Technology, Pasadena, CA, Ph.D., Molecular Genetics
1980 Michigan State University, East Lansing, MI, B.S., High Honors, Biochemistry

Postgraduate Training

1986-1992 Postdoctoral Research, Stanford University, Stanford, CA

Selected Publications

Peer-Reviewed Original Research Articles
1. Lazareva AA, Roman G, Mattox W, Hardin PE, Dauwalder B. A role for the adult fat body in Drosophila male courtship behavior. PLoS Genetics 3:115-122, 2007.
2. Qi J, Su S, Mattox W.. The doublesex splicing enhancer components Tra2 and Rbp1 also repress splicing through an intronic silencer. Molecular and Cellular Biology 27:699-708, 2007. PMID: 17101798.
3. Qi J, Su S, McGuffin ME, Mattox W.. Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing. Nucleic Acids Research 34:6256-6623, 2006. PMID: 17098939.
4. Xu DQ, Mattox W.. Identification of a splicing enhancer in MLH1 using COMPARE, a new assay for determination of relative RNA splicing efficiencies. Human Molecular Genetics 15:329-336, 2006. PMID: 16357104.
5. Unni E, Su S, Mattox W.. Analysis of a null mutation in the Drosophila splicing regulator Tra2 suggests its function is restricted to sexual differentiation. Genesis 37:76-83, 2003. PMID: 14595843.
6. Chandler DS, Qi J, Mattox W.. Direct repression of splicing by transformer-2. Molecular and Cellular Biology 23:5174-5185, 2003. PMID: 12861004.
7. Dauwalder B, Tsujimoto S, Moss J, Mattox W.. The takeout gene is regulated by the Drosophila sex determination pathway and affects male courtship behavior. Genes & Development 16:2879-2892, 2002. PMID: 12435630.
8. Chandler DS, McGuffin ME, Mattox W.. Functionally antagonistic sequences are required for normal autoregulation of Drosophila tra-2 pre-mRNA splicing. Nucleic Acids Research 29:3012-3019, 2001. PMID: 11452026.
9. Dauwalder B, Mattox W.. Analysis of RS domain functional specificity in vivo. EMBO Journal 17:6049-6060, 1998. PMID: 9774348.
10. McGuffin ME, Chandler D, Somaiya D, Dauwalder B, Mattox W. Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genetics 149:1477-1486, 1998. PMID: 9649535.
11. Bauer R, McGuffin ME, Mattox W, Tainsky MA.. Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor. Oncogene 17:1911-1922, 1998. PMID: 9788434.
12. Du C, McGuffin ME, Dauwalder B, Rabinow L, Mattox W.. Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila. Molecular Cell 2:741-750, 1998. PMID: 9885562.
13. Chandler D, McGuffin ME, Piskur J, Yao J, Baker BS, Mattox W.. Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2. Molecular and Cellular Biology 17:2908-2919, 1997. PMID: 9111363.
14. Cooper TA, Mattox W.. The regulation of splice-site selection, and its role in human disease. American Journal of Human Genetics 61:259-266, 1997. PMID: 9311728.
15. Dauwalder B, Amaya-Manzanares F, Mattox W.. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proceedings National Academy of Sciences 93:9004-9009, 1996. PMID: 8799144.

Last updated: 5/18/2009