Heads of Laboratories
Robert G. Roeder, Ph.D.
Arnold and Mabel Beckman Professor
Laboratory of Biochemistry and Molecular Biology
Differential gene expression, regulated primarily at the level of transcription, underlies key events in development, cell growth and differentiation, homeostasis, and pathologies such as cancer. The transcription programs central to these events are governed by cell-specific master transcription factors bound to specific enhancer and promoter elements, with the extraordinary power and significance of such factors being profoundly demonstrated by the ability of very small subsets to reprogram somatic cells to a pluripotent state. Dr. Roeder’s major objectives are to determine the mechanisms by which such factors, acting ultimately upon the general transcription machinery, activate or repress specific target genes in various physiological processes.
The actual transcription of protein-coding genes is mediated by RNA polymerase II and cognate initiation factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH) that form functional preinitiation complexes on promoters via an ordered assembly pathway that begins with recognition of common core promoter elements (e.g., TATA box) by the multisubunit TFIID. These factors — comprising the general transcription machinery — represent the ultimate targets of the various gene-specific factors. However, other “cofactors” are essential for functional communication between the gene-specific factors, to which they bind, and the general transcription machinery.
Dr. Roeder’s work is now heavily focused on these cofactors, many of which are structurally complex. They include cofactors (e.g., multi-subunit histone acetyl- and methyl-transferase complexes) that alter the structure of the natural chromatin template, cofactors (e.g., the 30-subunit Mediator) that act directly on the general transcription machinery, and a variety of cell/activator-specific cofactors (e.g., the B cellspecific OCA-B and the inducible PGC-1 implicated in energy metabolism).
Current activities focus on transcriptional activators important for homeostasis (nuclear hormone receptors); lymphoid cell differentiation (E2A, OCT1/2, OCA-B) and malignancy (E2A-PBX1, AML1-ETO, and MLL1-AF9 leukemogenic fusion proteins); and tumor suppression (p53).
Dr. Roeder received his Ph.D. in biochemistry in 1969 from the University of Washington, Seattle, where he worked with William Rutter. He did postdoctoral work with Donald D. Brown at the Carnegie Institution of Washington from 1969 to 1971. He was a member of the faculty at the Washington University School of Medicine in St. Louis from 1971 until 1982, when he joined Rockefeller. In 1985 he was named Arnold and Mabel Beckman Professor. Dr. Roeder received the 2010 Salk Institute Medal for Research Excellence and the 2003 Albert Lasker Basic Medical Research Award. He shared the 2002 ASBMB-Merck Award, the 2000 Gairdner Foundation International Award, the 1999 Louisa Gross Horwitz Prize and the 1999 General Motors Cancer Research Foundation’s Alfred P. Sloan Prize. He is a member of the National Academy of Sciences.
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