Biography
Education:
- BA University of Texas at Austin (USA)
- PhD University of Virginia (USA)
Memberships:
- Member of the National Academy of Sciences (USA)
- Member of the American Academy of Arts and Sciences (USA)
- Member of the Harvey Society, Rockefeller University (USA)
- Member of the American Society for Biochemistry and Molecular Biology (USA)
- Member of the American Chemical Society (USA)
- Member of the Institute of Medicine (USA)
Research Interests:
Genes are switched on and off in eukaryotic cells via regulatory proteins commonly termed transcription factors. The research focus of the McKnight laboratory centers on a subset of transcription factors that are gene specific. In the simplest of terms, a gene may be subject to regulation by a given transcription factor if it contains high affinity binding sites for that factor in a functionally relevant region - promoter, enhancer or silencer. This simplistic dogma is complicated by a variety of complexities that have emerged from studies of eukaryotic gene regulation over the past decade. For example, individual transcription factors tend to exist as members of multiprotein families whose DNA binding activities can be indistinguishable when analyzed as isolated biochemical entities. It is therefore problematic to assess which member of a related family is responsible for a given regulatory event. It has also been recognized that gene specific transcription factors can obligatorily rely on heteromeric partners. A competent DNA binding version, that is, may rely on the formation of a protein complex consisting of two or more entirely distinct polypeptides. In certain cases, gene specific transcription factors retain the ability to bind DNA avidly, yet are unable to functionally regulate transcription at the level of activation or repression without the help of co-activator or co-repressor proteins. Finally, the biologic activities of transcription factors are universally regulated in living cells by either covalent post-translational modification, including phosphorylation and proteolysis, or by non-covalent interaction with small molecule metabolites or ligands. Such regulatory processes can modulate a myriad of potential fates of transcription factors including intracellular localization, stability, intermolecular oligomerization or intramolecular folding. The McKnight laboratory seeks to understand the regulation of transcription factor function at a biochemical level with keen attention to biological relevance.
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