Steven L. McKnight, Ph.D.

Tuesday, Sept. 26, 2006, 10 a.m. – 10:30 a.m.

Searle Center Lecture Hall

The McKnight lab has studied two highly related CNS-enriched transcription factors designated neuronal PAS domain proteins 1 (NPAS1) and NPAS3. The genes encoding these proteins are orthologous to the Trachealess gene of fruit flies.

 

Evidence will be presented indicating that mice deficient in the NPAS1 and NPAS3 transcription factors display behavioral deficits reminiscent of psychosis. These observations are bolstered by recent human genetic studies of a family suffering schizophrenia wherein affected family members have been found to carry an inactivating mutation in the human NPAS3 gene.

 

Recent studies from the McKnight lab provide evidence that the pathway regulated by the NPAS3 transcription factor is essential for neurogenesis emanating from the dentate gyrus of the adult mouse brain. This pathway, as in the case of the pathway regulating branching morphogenesis of the tracheal system in fruit fly larvae, involves fibroblast growth factor (FGF), the FGF receptor, and Sprouty - an intracellular inhibitor of FGF signaling.

 

Finally, biochemical studies of the mammalian Sprouty proteins have provided evidence that this protein forms a very large, virus-like particle, having the properties of a miniature battery. Dr. McKnight will speculate on the biological utility of "nanobatteries" formed by the Sprouty and related Spred proteins.

Steve McKnight received his B.S. in biology from the University of Texas in 1974, and his Ph.D. in biology from the University of Virginia in 1977. His independent scientific career was initiated at the Embryology Department of the Carnegie Institution of Washington in 1977. There he used molecular biological and biochemical approaches to study how genes are turned on and off in mammalian cells. In 1991, McKnight moved to California to co-found, together with Bob Tjian and Dave Goeddel, a biotechnology company called Tularik, Inc. In 1995, McKnight moved to UT Southwestern Medical Center where he remains employed as a Professor of Biochemistry.

 

McKnight serves on the Scientific Advisory Board of the Howard Hughes Medical Institute and on the Board of Trustees of the Carnegie Institution of Washington. He is a fellow of the American Society for Microbiology, and an elected member of the National Academy of Sciences, the Institute of Medicine, and the Academy of Arts and Sciences.