Robert G. Roeder

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Robert G. Roeder (born June 3, 1942 in Boonville, Indiana, United States) is an American biologist. He is known as a pioneer in eukaryotic transcription. He is the recipient of the Gairdner Foundation International Award in 2000 and the Albert Lasker Award for Basic Medical Research in 2003. He currently serves as Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemical and Molecular Biology at The Rockefeller University.

Biography

Roeder was born in Boonville, Indiana, USA in 1942. He received his B.A. summa cum laude in chemistry from Wabash College and his M.S. in chemistry from the University of Illinois. He received his Ph.D. in biochemistry in 1969 from the University of Washington, Seattle, where he worked with William J. Rutter. He did postdoctoral work with Donald D. Brown at the Carnegie Institution of Washington, in Baltimore, from 1969 to 1971. He was a member of the faculty at Washington University School of Medicine in St. Louis from 1971 to 1982, when he joined The Rockefeller University. In 1985, he was named Arnold and Mabel Beckman Professor. He was elected as a member of the National Academy of Sciences in 1988 and the American Academy of Arts and Sciences in 1995, and a foreign associate member of the European Molecular Biology Organization in 2003.

Major Discoveries

  • 1969-1977: In 1969, as a graduate student at the University of Washington, Roeder discovers that three enzymes, called RNA polymerases, directly copy DNA in animal cells.[1] As a professor at Washington University in St. Louis, he goes on to show that these enzymes, referred to as Pol I, II and III, recognize and copy distinct classes of genes.[2][3][4]
  • 1977-1979: Roeder develops cell-free systems to better study transcription.[5][6][7] Composed of the purified RNA polymerases and components extracted from cell nuclei, the systems allow researchers to recreate transcription in a test tube in a way that faithfully mimics the real process in cells.
  • 1980: The development of cell-free systems leads to the identification of complex sets of proteins called accessory factors that are essential for each individual RNA polymerase (e.g., TFIIA, TFIIB, TFIIE, TFIIF and TFIIH for Pol II, and TFIIIB and TFIIIC for Pol III) to "read" specific target genes.[8][9]
  • 1980: Roeder identifies the first mammalian gene-specific activator, called TFIIIA.[10] TFIIIA and similar proteins bind to specific DNA sequences and enhance the reading of corresponding target genes. Repressors perform the opposite task by inhibiting a gene's activity.
  • 1990s: A decade of research culminates with the discovery of coactivators, large protein complexes that provide a bridge between the activators and repressors and the RNA polymerases and other components of the general transcription machinery.[11][12]
  • 1992: Roeder's laboratory demonstrates that coactivators can be ubiquitous, monitoring many genes in a variety of cells, or specific to one particular cell type. Roeder and colleagues introduce the concept of cell specificity after they demonstrate that the coactivator OCA-B, the first cell-specific coactivator, discovered by Roeder in 1992, is unique to immune system B cells.[13]
  • 1996: Roeder's laboratory discovers the major conduit for communication between gene-specific activators and the general transcription machinery in animal cells: a giant coactivator (TRAP/SMCC) that consists of about 25 different protein chains and is referred to as the human mediator after its counterpart in yeast.[14]
  • 2002: Roeder and colleagues show that a single component of the mediator is essential for the formation of fat cells — a finding that may one day contribute to new treatments for diabetes, heart disease, cancer and other conditions in which the fat-making process breaks down.[15]

Highly Cited Papers

  • 1. Dignam, J. D., Lebovitz, R. M., and Roeder, R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res., 11: 1475-1489, 1983. Times Cited: 9,404
  • 2. Gu, W. and Roeder, R. G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell, 90: 595-606, 1997. Times Cited: 1,184
  • 3. Sawadogo, M. and Roeder, R. G. Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell, 43: 165-175, 1985. Times Cited: 1,046
  • 4. Dignam, J. D., Martin, P. L., Shastry, B. S., and Roeder, R. G. Eukaryotic gene transcription with purified components. Methods Enzymol., 101: 582-598, 1983. Times Cited: 750
  • 5. Roeder, R. G. and Rutter, W. J. Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms. Nature, 224: 234-237, 1969. Times Cited: 726

Honors and awards

Prominent Alumni of the Roeder Laboratory

The Roeder Laboratory has trained hundreds of students and postdoctoral fellows, many of whom hold independent positions in prominent biomedical research institutions, including Richard A. Bernstein (Northwestern University), Robert B. Darnell (Rockefeller University and HHMI), Beverly M. Emerson (Salk Institute for Biological Studies), Michael R. Green (University of Massachusetts Medical School and HHMI), Wei Gu (Columbia University), Nathaniel Heintz (Rockefeller University and HHMI), Andrew B. Lassar (Harvard Medical School), Carl S. Parker (California Institute of Technology), Ron Prywes (Columbia University), Danny Reinberg (New York University School of Medicine and HHMI), Hazel L. Sive (Massachusetts Institute of Technology and Whitehead Institute) and Jerry Workman (Stowers Institute for Medical Research).[29]

References

  1. Roeder RG, Rutter WJ (Oct 1969). "Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms". Nature 224 (5216): 234–7. doi:10.1038/224234a0. PMID 5344598. 
  2. Reeder RH, Roeder RG (Jun 1972). "Ribosomal RNA synthesis in isolated nuclei". J Mol Biol 67 (3): 433–41. doi:10.1016/0022-2836(72)90461-5. PMID 4558099. 
  3. Weinmann R, Roeder RG (May 1974). "Role of DNA-Dependent RNA Polymerase III in the Transcription of the tRNA and 5S RNA Genes". Proc Natl Acad Sci U S A 71 (5): 1790–4. doi:10.1073/pnas.71.5.1790. PMC 388326. PMID 4525293. 
  4. Weinmann R, Raskas HJ, Roeder RG (Sep 1974). "Role of DNA-Dependent RNA Polymerases II and III in Transcription of the Adenovirus Genome Late in Productive Infection". Proc Natl Acad Sci U S A 71 (9): 3426–39. doi:10.1073/pnas.71.9.3426. PMC 433786. PMID 4530313. 
  5. Parker CS, Roeder RG (Jan 1977). "Selective and accurate transcription of the Xenopus laevis 5S RNA genes in isolated chromatin by purified RNA polymerase III". Proc Natl Acad Sci U S A 74 (1): 44–8. doi:10.1073/pnas.74.1.44. PMC 393193. PMID 264693. 
  6. Ng SY, Parker CS, Roeder RG (Jan 1979). "Transcription of cloned Xenopus 5S RNA genes by X. laevis RNA polymerase III in reconstituted systems". Proc Natl Acad Sci U S A 76 (1): 136–40. doi:10.1073/pnas.76.1.136. PMC 382891. PMID 284325. 
  7. Weil PA, Luse DS, Segall J, Roeder RG (Oct 1979). "Selective and accurate initiation of transcription at the Ad2 major late promotor in a soluble system dependent on purified RNA polymerase II and DNA". Cell 18 (2): 469–84. doi:10.1016/0092-8674(79)90065-5. PMID 498279. 
  8. Segall J, Matsui T, Roeder RG (Dec 1980). "Multiple factors are required for the accurate transcription of purified genes by RNA polymerase III". J Biol Chem 255 (24): 11986–91. PMID 7440579. 
  9. Matsui T, Segall J, Weil PA, Roeder RG (Dec 1980). "Multiple factors required for accurate initiation of transcription by purified RNA polymerase II". J Biol Chem 255 (24): 11992–6. PMID 7440580. 
  10. Engelke DR, Ng SY, Shastry BS, Roeder RG (Mar 1980). "Specific interaction of a purified transcription factor with an internal control region of 5S RNA genes". Cell 19 (3): 717–28. doi:10.1016/S0092-8674(80)80048-1. PMID 6153931. 
  11. Meisterernst M, Roy AL, Lieu HM, Roeder RG (Sep 1991). "Activation of class II gene transcription by regulatory factors is potentiated by a novel activity". Cell 66 (5): 981–93. doi:10.1016/0092-8674(91)90443-3. PMID 1889091. 
  12. Ge H, Roeder RG (Aug 1994). "Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes". Cell 78 (3): 513–23. doi:10.1016/0092-8674(94)90428-6. PMID 8062391. 
  13. Luo Y, Fujii H, Gerster T, Roeder RG (Oct 1992). "A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors". Cell 71 (2): 231–41. doi:10.1016/0092-8674(92)90352-D. PMID 1423591. 
  14. Fondell JD, Ge H, Roeder RG (Aug 1996). "Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex". Proc Natl Acad Sci U S A 93 (16): 8329–33. doi:10.1073/pnas.93.16.8329. PMC 38670. PMID 8710870. 
  15. Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG (May 2002). "Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis". Nature 417 (6888): 563–7. doi:10.1038/417563a. PMID 12037571. 
  16. ACS Biological Chemistry: Achievement and Travel Awards
  17. National Academy of Sciences Award in Molecular Biology
  18. Lewis S. Rosenstiel Award
  19. The Passano Foundation
  20. The Official Site of Louisa Gross Horwitz Prize
  21. General Motors Cancer Research Foundation Awards Honor Top Cancer Innovators
  22. The Gairdner Foundation
  23. Science 2001 Dickson Prize Lecturer
  24. ASBMB-Merck Award
  25. The Lasker Foundation
  26. Washington University to confer five honorary degrees May 20, 2005
  27. Salk Institute Medals to be awarded to Pioneering Biologist Robert Roeder and High-Tech Innovator/Philanthropist Irwin Jacobs
  28. 'Towering Figures' in Cell Research to Share Albany Medical Center Prize
  29. Abmayr SM, Workman JL (Oct 2003). "Transcription factors prominently in Lasker Award to Roeder". Cell 115 (3): 243–6. doi:10.1016/S0092-8674(03)00846-8. PMID 14636549. 

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