Steven L. McKnight received a bachelor’s degree in biology from the University of Texas in 1974 and his Ph.D. degree in biology from the University of Virginia in 1977. He conducted postdoctoral research at the Carnegie Institution for Science under the mentorship of Donald Brown and was appointed as a staff member of that institution in 1983. He was appointed as a Howard Hughes Medical Institute investigator in 1988.
His research focus at the Carnegie Institution was on gene regulation. He used molecular biological methods to define the regulatory DNA sequences constituting the promoter of the herpes simplex virus thymidine kinase gene. He then employed biochemical methods to purify gene specific transcription factors including members of the C/EBP and GABP families of gene regulatory proteins. The latter studies helped elucidate the concepts of homotypic and heterotypic dimerization of transcription factor subunits via an unusually simple structural motif called the leucine zipper.
In 1991, McKnight left academia to co-found Tularik, a San Francisco-based biotechnology company devoted to the discovery of ethical drugs acting to treat disease state via the regulation of gene expression. In 1995, he moved from Tularik to UT Southwestern Medical Center, and in 1996 he was appointed as chairman of the department of biochemistry. Over the past 20 years, McKnight has directed an active research laboratory and has guided the department of biochemistry to substantial growth in the disciplines of chemistry, biochemistry, and biophysics. His current research is focused on two topics, including experiments facilitating the test tube reconstitution of RNA granules important for spatially localized regulation of translation and the discovery and mechanistic characterization of a neuroprotective chemical.