Steven McKnight

Bio: Steve McKnight received his PhD degree in biology at the University of Virginia in 1977. He then worked at the Department of Embryology of the Carnegie Insititution of Washington between 1977 and 1991 where he studied how genes switch on and off in mammalian cells. In 1991 he moved to San Francisco to co-found, with Dave Goeddel and Bob Tjian, a biotechnology company called Tularik, Inc. In 1996 McKnight moved to the University of Texas Southwestern Medical Center where he remains employed as professor and chair of the Department of Biochemistry. McKnight's work over the past decade has focused on regulatory proteins endowed with the capacity to sense light, redox potential and molecular gasses. His biochemical studies have helped elucidate regulatory pathways ranging from hypoxia response to circadian rhythm.

Talk Title: Schizophrenia, Stem Cells and Sprouty Signaling

Abstract: Mice bearing targeted mutations in the NPAS1 and NPAS3 transcription factors display behavioral and pathophysiological deficits reminiscent of schizophrenia. That the pathways regulated by these transcription factors might indeed be relevant to human psychosis is supported by the discovery of a translocation in the NPAS3 gene in a Canadian family suffering from schizophrenia. Evidence will be presented indicating that the NPAS3 transcription factor is required in support of adult hippocampal neurogenesis. NPAS3-deficient animals are almost completely devoid of adult neurogenesis in the granular layer of the dentate gyrus. It is hypothesized that the behavioral and pathophysiological deficits characteristic of NPAS3-deficient animals may relate, at least in part, to impaired adult neurogenesis. The NPAS3 transcription factor drives a pathway involving fibroblast growth factor (FGF), FGF receptor and Sprouty. Recent biochemical studies of Sprouty in the McKnight lab have revealed a prosthetic iron:sulfur complex endowing the protein with the ability to pass electrons and sense nitric oxide. Surprisingly, biochemical studies have also shown that the Sprouty - and related SPRED proteins -assemble into huge, monodisperse oligomeric complexes. It is speculated that these protein assemblies may, like the E2 core of pyruvate dehydrogenase, utilize electron transport in their ultimate functional roles.