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Robert G. Roeder

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Robert G. Roeder
Born
Robert Gayle Roeder

(1942-06-03) June 3, 1942 (age 82)
Boonville, Indiana, United States
NationalityAmerican
Alma materUniversity of Washington, University of Illinois, Wabash College
Known for
Awards
Scientific career
Fields
InstitutionsWashington University in St. Louis
Rockefeller University
ThesisMultiple RNA Polymerases and RNA Synthesis in Eukaryotic Systems (1969)
Doctoral advisorWilliam J. Rutter
Other academic advisorsDonald D. Brown
Doctoral students

Robert G. Roeder (born June 3, 1942, in Boonville, Indiana, United States) is an American biochemist. He is known as a pioneer scientist in eukaryotic transcription. He discovered three distinct nuclear RNA polymerases in 1969 [1] and characterized many proteins involved in the regulation of transcription, including basic transcription factors and the first mammalian gene-specific activator over five decades of research.[2] He is the recipient of the Gairdner Foundation International Award in 2000, the Albert Lasker Award for Basic Medical Research in 2003, and the Kyoto Prize in 2021. He currently serves as Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemical and Molecular Biology at The Rockefeller University.

Biography

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Roeder was born in Boonville, Indiana, US in 1942. He received his B.A. summa cum laude in chemistry from Wabash College in 1964 and his M.S. in chemistry from the University of Illinois in 1965. 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 scientific discoveries

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  • 1969: As a graduate student at the University of Washington, Roeder discovers that three enzymes, called RNA polymerases, directly copy DNA to RNA in eukaryotic organisms ranging from yeast to mammals.[1]
  • 1971–1977: 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, have complex subunit structures with both distinct and common polypeptides, recognize and copy distinct classes of genes, respectively, of large ribosomal RNAs, mRNA precursors, and transfer and 5S RNAs.[3][4][5][6]
  • 1977–1979: Roeder develops cell-free systems to better study transcription.[7][8] 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.[9][10]
  • 1979–1980: 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.[11][12][13]
  • 1980: Roeder identifies the first mammalian gene-specific activator, called TFIIIA.[14] 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.[15][16]
  • 1992: Roeder 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.[17]
  • 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.[18]
  • 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.[19]

Highly cited papers

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  1. Dignam, J. D.; Lebovitz, R. M.; Roeder, R. G. (March 11, 1983). "Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei". Nucleic Acids Research. 11 (5). Oxford University Press (OUP): 1475–1489. doi:10.1093/nar/11.5.1475. ISSN 0305-1048. PMC 325809. PMID 6828386. Times Cited: 12,743
  2. Gu, Wei; Roeder, Robert G (1997). "Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain". Cell. 90 (4). Elsevier BV: 595–606. doi:10.1016/s0092-8674(00)80521-8. ISSN 0092-8674. PMID 9288740. S2CID 18434280. Times Cited: 3,236
  3. Roeder, Robert G (1996). "The role of general initiation factors in transcription by RNA polymerase II". Trends in Biochemical Sciences. 21 (9). Elsevier BV: 327–335. doi:10.1016/S0968-0004(96)10050-5. ISSN 0968-0004. PMID 8870495. Times Cited: 1,511
  4. Sawadogo, M (1985). "Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region". Cell. 43 (1). Elsevier BV: 165–175. doi:10.1016/0092-8674(85)90021-2. ISSN 0092-8674. PMID 4075392. S2CID 42562115.Times Cited: 1,377
  5. Roeder, Robert G.; Rutter, William J. (1969). "Multiple Forms of DNA-dependent RNA Polymerase in Eukaryotic Organisms". Nature. 224 (5216). Springer Science and Business Media LLC: 234–237. Bibcode:1969Natur.224..234R. doi:10.1038/224234a0. ISSN 0028-0836. PMID 5344598. S2CID 4283528. Times Cited: 1,177

Honors and awards

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Prominent alumni of the Roeder Laboratory

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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).[37]

References

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  1. ^ a b Roeder RG, Rutter WJ (October 1969). "Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms". Nature. 224 (5216): 234–7. Bibcode:1969Natur.224..234R. doi:10.1038/224234a0. PMID 5344598. S2CID 4283528.
  2. ^ Roeder RG (September 2019). "50+ years of eukaryotic transcription: an expanding universe of factors and mechanisms". Nature Structural & Molecular Biology. 26 (9): 783–791. doi:10.1038/s41594-019-0287-x. PMC 6867066. PMID 31439941.
  3. ^ Sklar VE, Schwartz LB, Roeder RG (January 1975). "Distinct molecular structures of nuclear class I, II and III DNA-dependent RNA polymerases". Proc Natl Acad Sci U S A. 72 (1): 348–52. Bibcode:1975PNAS...72..348S. doi:10.1073/pnas.72.1.348. PMC 432302. PMID 1054509.
  4. ^ Reeder RH, Roeder RG (June 1972). "Ribosomal RNA synthesis in isolated nuclei". J Mol Biol. 67 (3): 433–41. doi:10.1016/0022-2836(72)90461-5. PMID 4558099.
  5. ^ 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. Bibcode:1974PNAS...71.1790W. doi:10.1073/pnas.71.5.1790. PMC 388326. PMID 4525293.
  6. ^ Weinmann R, Raskas HJ, Roeder RG (September 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. Bibcode:1974PNAS...71.3426W. doi:10.1073/pnas.71.9.3426. PMC 433786. PMID 4530313.
  7. ^ Parker CS, Roeder RG (January 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. Bibcode:1977PNAS...74...44P. doi:10.1073/pnas.74.1.44. PMC 393193. PMID 264693.
  8. ^ Ng SY, Parker CS, Roeder RG (January 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. Bibcode:1979PNAS...76..136N. doi:10.1073/pnas.76.1.136. PMC 382891. PMID 284325.
  9. ^ Weil PA, Luse DS, Segall J, Roeder RG (October 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. S2CID 34095322.
  10. ^ Parker CS, Jaehning JA, Roeder RG (1978). "Faithful gene transcription by eukaryotic RNA polymerases in reconstructed systems". Cold Spring Harb Symp Quant Biol. 42 (1): 577–87. doi:10.1101/sqb.1978.042.01.060. PMID 277365.
  11. ^ Segall J, Matsui T, Roeder RG (December 1980). "Multiple factors are required for the accurate transcription of purified genes by RNA polymerase III". J Biol Chem. 255 (24): 11986–91. doi:10.1016/S0021-9258(19)70231-2. PMID 7440579.
  12. ^ Matsui T, Segall J, Weil PA, Roeder RG (December 1980). "Multiple factors required for accurate initiation of transcription by purified RNA polymerase II". J Biol Chem. 255 (24): 11992–6. doi:10.1016/S0021-9258(19)70232-4. PMID 7440580.
  13. ^ Roeder RG, Engelke DR, Luse DS, Segall J, Shastry BS, Weil PA (1979). "Factors involved in the transcription of purified genes by RNA polymerase III". ICN-UCLA Symposium on Gene Regulation in Eukaryote. eds. R. Axel and T. Maniatis. Academic Press, New York: 521–540.
  14. ^ Engelke DR, Ng SY, Shastry BS, Roeder RG (March 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. S2CID 23955175.
  15. ^ Meisterernst M, Roy AL, Lieu HM, Roeder RG (September 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. S2CID 43608887.
  16. ^ Ge H, Roeder RG (August 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. S2CID 1140379.
  17. ^ Luo Y, Fujii H, Gerster T, Roeder RG (October 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. S2CID 24583386.
  18. ^ Fondell JD, Ge H, Roeder RG (August 1996). "Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex". Proc Natl Acad Sci U S A. 93 (16): 8329–33. Bibcode:1996PNAS...93.8329F. doi:10.1073/pnas.93.16.8329. PMC 38670. PMID 8710870.
  19. ^ 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. Bibcode:2002Natur.417..563G. doi:10.1038/417563a. PMID 12037571. S2CID 4432077.
  20. ^ ACS Biological Chemistry: Achievement and Travel Awards
  21. ^ National Academy of Sciences Award in Molecular Biology
  22. ^ Lewis S. Rosenstiel Award Archived July 25, 2008, at the Wayback Machine
  23. ^ The Passano Foundation
  24. ^ The Official Site of Louisa Gross Horwitz Prize
  25. ^ Volkers, N. (July 7, 1999). "General Motors Cancer Research Foundation Awards Honor Top Cancer Innovators". JNCI Journal of the National Cancer Institute. 91 (13): 1107–1108. doi:10.1093/jnci/91.13.1107. ISSN 0027-8874. PMID 10393714.
  26. ^ The Gairdner Foundation
  27. ^ Science 2001 Dickson Prize Lecturer Archived June 26, 2007, at the Wayback Machine
  28. ^ ASBMB-Merck Award[permanent dead link‍]
  29. ^ The Lasker Foundation
  30. ^ McGinn, Susan Killenberg (May 5, 2005). "Washington University to confer five honorary degrees May 20 – The Source – Washington University in St. Louis". The Source. Retrieved August 11, 2023.
  31. ^ "Salk Institute Medals to be awarded to Pioneering Biologist Robert Roeder and High-Tech Innovator/Philanthropist Irwin Jacobs". Salk Institute for Biological Studies. Retrieved August 11, 2023.
  32. ^ "'Towering Figures' in Cell Research to Share Albany Medical Center Prize". Archived from the original on October 2, 2015. Retrieved April 14, 2012.
  33. ^ "Roeder 'a consumate biochemist and absolute perfect fit' for the honor". www.asbmb.org. Retrieved August 11, 2023.
  34. ^ "105th Howard Taylor Ricketts Lecture -"Transcriptional regulatory mechanisms in animal cells" – University of Chicago – Department of Medicine". medicine.uchicago.edu. Retrieved August 11, 2023.
  35. ^ "Shizhang Bei International Award". en.bsc.org.cn. Retrieved August 11, 2023.
  36. ^ 2021 Kyoto Prize Laureates – Discovery of the Principle of Gene Transcription Mechanisms in Eukaryotes
  37. ^ Abmayr SM, Workman JL (October 2003). "Transcription factors prominently in Lasker Award to Roeder". Cell. 115 (3): 243–6. doi:10.1016/S0092-8674(03)00846-8. PMID 14636549. S2CID 17097436.
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