H. Robert Horvitz
|H. Robert Horvitz|
Howard Robert Horvitz|
May 8, 1947
|Known for||Apoptosis research|
|Institutions||Massachusetts Institute of Technology|
|Thesis||Modifications of the host RNA polymerase induced by coliphage T4 (1974)|
|Notable students||Junying Yuan|
Howard Robert Horvitz (born May 8, 1947) is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston.
Education and early life
Horvitz was born in Chicago, Illinois to Jewish parents, the son of Mary R. (Savit), a school teacher, and Oscar Freedom Horvitz, a GAO accountant. He majored in mathematics at Massachusetts Institute of Technology, where he joined Alpha Epsilon Pi and spent his summers working for IBM, at first wiring panels for accounting machines and then in his final summer helping to develop IBM's Conversational Programming System.
During his senior year, Horvitz took his first courses in biology and was encouraged by his professors to continue to study biology in graduate school, despite his limited coursework in the field. After he completed his undergraduate studies in 1968, he enrolled in graduate studies in biology at Harvard University, where he studied T4-induced modifications of E. coli RNA polymerase under the direction of Walter Gilbert and James Watson. He completed his PhD in 1974.
In 1974, Horvitz took a postdoctoral position at the Laboratory of Molecular Biology (LMB) in Cambridge, England, where he worked with his future Nobel prize co-winners Sydney Brenner and John Sulston on the genetics and cell lineage of C. elegans. In 1978, Horvitz was offered a faculty position at MIT, where he is currently Professor of Biology and a member of the McGovern Institute for Brain Research. He is also an Investigator of the Howard Hughes Medical Institute.
At LMB, Horvitz worked with Sulston to track every non-gonadal cell division that occurred during larval development, and published a complete description of these lineages in 1977. Later, in cooperation with Sulston and Martin Chalfie, Horvitz began investigations first characterizing several cell lineage mutants and then seeking genes that controlled cell lineage or that controlled specific linages. In 1981, they identified and characterized the gene lin-4, a "heterochronic" mutant that changes the timeline of cell fates.
In his early work at MIT, Horvitz continued his work on cell lineage and cell fate, using C. elegans to investigate whether there was a genetic program controlling cell death, or apoptosis. In 1986, he identified the first "death genes", ced-3 and ced-4. He showed that functional ced-3 and ced-4 genes were a prerequisite for cell death to be executed. He went on to show that another gene, ced-9, protects against cell death by interacting with ced-4 and ced-3, as well as identifying a number of genes that direct how a dead cell is eliminated. Horvitz showed that the human genome contains a ced-3-like gene.
Horvitz's later research continued to use C. elegans to analyze the genetic control of animal development and behavior, as well as to link discoveries in the nematode to human diseases, particularly cancer and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). He made further advancements in defining the molecular pathway of programmed cell death, and has identified several key components, including: EGL-1, a protein which activates apoptosis by inhibiting CED-9; transcription factors ces-1 and ces-2, and ced-8, which controls the timing of cell death. He has also continued work on heterochronic mutants and other aspects of cell lineage, and established lines of research in signal transduction, morphogenesis, and neural development. Horvitz has collaborated with Victor Ambros and David Bartel on a project to characterize the complete set of the more than 100 microRNAs in the C. elegans genome.
- Sulston, J.E.; Horvitz, H.R. (March 1977). "Post-embryonic cell lineages of the nematode, Caenorhabditis elegans". Developmental Biology. 56 (1): 110–156. doi:10.1016/0012-1606(77)90158-0. PMID 838129.
- Ellis, Hillary M.; Horvitz, H. Robert (28 March 1986). "Genetic control of programmed cell death in the nematode C. elegans". Cell. 44 (6): 817–829. doi:10.1016/0092-8674(86)90004-8. PMID 3955651.
- Ellis, R E; Yuan, J; Horvitz, H R (November 1991). "Mechanisms and Functions of Cell Death". Annual Review of Cell Biology. 7 (1): 663–698. doi:10.1146/annurev.cb.07.110191.003311. PMID 1809356.
- Yuan, J; Shaham, S; Ledoux, S; Ellis, HM; Horvitz, HR (19 November 1993). "The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme". Cell. 75 (4): 641–52. doi:10.1016/0092-8674(93)90485-9. PMID 8242740.
- Hengartner, MO; Horvitz, HR (25 February 1994). "C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2". Cell. 76 (4): 665–76. doi:10.1016/0092-8674(94)90506-1. PMID 7907274.
Awards and honors
- 1986 Spencer Award in Neurobiology from Columbia University
- 1986 Warren Triennial Prize from the Massachusetts General Hospital
- 1988 U.S. Steel Foundation Award in Molecular Biology from the U.S. National Academy of Sciences
- 1991 Member, U.S. National Academy of Sciences
- 1993 V.D. Mattia Award (Roche Institute of Molecular Biology)
- 1994 Member, American Academy of Arts and Sciences
- 1994 Hans Sigrist Prize from the University of Bern, Switzerland
- 1995 Charles A. Dana Award
- 1996 Ciba-Drew Award for Biomedical Science
- 1997 Rosenstiel Award
- 1998 Passano Award for the Advancement of Medical Science
- 1998 General Motors Research Foundation, Alfred P. Sloan, Jr. Prize
- 1999 Gairdner Foundation International Award
- 2000 Paul Ehrlich and Ludwig Darmstaedter Prize
- 2000 Segerfalk Award
- 2000 March of Dimes Prize in Developmental Biology
- 2000 Louisa Gross Horwitz Prize for Biology or Biochemistry
- 2000 Grand Prix Charles-Leopold Mayer (French Academy of Sciences)
- 2001 Bristol -Myers Squibb Award for Distinguished Achievement in Neuroscience
- 2001 Genetics Society of America Medal
- 2002 Nobel Prize in Physiology or Medicine with Sydney Brenner and John Sulston
- 2002 Wiley Prize in Biomedical Sciences
- 2002 Gruber Foundation Genetics Prize
- 2003 Member, Institute of Medicine
- 2007 UK Genetics Society Mendel Medal
- 2009 Elected a Foreign Member of the Royal Society (ForMemRS)
- Green, David B. (8 May 2015). "Biologist who discovered death genes' through worm research is born". This Day in Jewish History. Haaretz. Retrieved 18 September 2015.
- "H. Robert Horvitz – Nobel diploma". Nobel Prizes and Laureates. NobelPrize.org. Retrieved 18 September 2015.
- "Fellows of the Royal Society". London: Royal Society. Archived from the original on 2015-03-16.
- Horvitz, H. Robert (30 May 2012). "Genetic Control of Nematode Development and Behavior". Our scientists. Howard Hughes Medical Institute. Retrieved 18 September 2015.
- "H. Robert Horvitz – Curriculum Vitae". Nobel Prizes and Laureates. NobelPrize.org. Retrieved 18 September 2015.
- "H. Robert Horvitz – Autobiography". Nobel Prizes and Laureates. NobelPrize.org. Retrieved 18 September 2015.[permanent dead link]
- "H. Robert Horvitz - Biographical". www.nobelprize.org. Retrieved 2016-01-26.
- "USA Science and Engineering Festival - Advisors". Usasciencefestival.org. Archived from the original on 2010-04-21. Retrieved 2013-04-23.
- Horvitz, H. Robert (8 December 2002). "Worms, Life and Death: Nobel Lecture" (PDF). Nobelprize.org. Nobel Media. Retrieved 26 January 2016.
- Sulston, J.E.; Horvitz, H.R. (1977). "Post-embryonic Cell Lineages of the Nematode, Caenorhabditis elegans" (PDF). Developmental Biology. 56: 110–156. doi:10.1016/0012-1606(77)90158-0. PMID 838129. Retrieved 26 January 2016.
- Horvitz, H. R.; Sulston, J. E. (1980-10-01). "Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans". Genetics. 96 (2): 435–454. ISSN 0016-6731. PMC . PMID 7262539.
- Sulston, John E.; Horvitz, H. Robert (1981-02-01). "Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans". Developmental Biology. 82 (1): 41–55. doi:10.1016/0012-1606(81)90427-9.
- Chalfie, M.; Horvitz, H. R.; Sulston, J. E. (1981-04-01). "Mutations that lead to reiterations in the cell lineages of C. elegans". Cell. 24 (1): 59–69. doi:10.1016/0092-8674(81)90501-8. ISSN 0092-8674. PMID 7237544.
- Ellis, Hilary M.; Horvitz, H. Robert (1986-03-28). "Genetic control of programmed cell death in the nematode C. elegans". Cell. 44 (6): 817–829. doi:10.1016/0092-8674(86)90004-8. PMID 3955651.
- Ellis, Ronald E.; Yuan, Junying; Horvitz, H. Robert (1991-01-01). "Mechanisms and Functions of Cell Death". Annual Review of Cell Biology. 7 (1): 663–698. doi:10.1146/annurev.cb.07.110191.003311. PMID 1809356.
- "MIT's Horvitz shares Nobel Prize in physiology". MIT News. Retrieved 2016-01-26.
- Conradt, B.; Horvitz, H. R. (1998-05-15). "The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9". Cell. 93 (4): 519–529. doi:10.1016/s0092-8674(00)81182-4. ISSN 0092-8674. PMID 9604928.
- Metzstein, M. M.; Horvitz, H. R. (1999-09-01). "The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein". Molecular Cell. 4 (3): 309–319. doi:10.1016/s1097-2765(00)80333-0. ISSN 1097-2765. PMID 10518212.
- Metzstein, Mark M.; Hengartner, Michael O.; Tsung, Nancy; Ellis, Ronald E.; Horvitz, H. Robert (1996-08-08). "Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2". Nature. 382 (6591): 545–547. doi:10.1038/382545a0. PMID 8700229.
- Stanfield, G. M.; Horvitz, H. R. (2000-03-01). "The ced-8 gene controls the timing of programmed cell deaths in C. elegans". Molecular Cell. 5 (3): 423–433. doi:10.1016/s1097-2765(00)80437-2. ISSN 1097-2765. PMID 10882128.
- "The Horvitz Laboratory". web.mit.edu. Retrieved 2016-01-26.
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- "NAS award in molecular biology". National Academy of Sciences. Retrieved 20 May 2016.
- "Hans Sigrist Prize Winners". University of Bern. Retrieved 20 May 2016.
- "Horwitz Prize Goes To MIT's Horvitz, Harvard's Korsmeyer". Columbia University Record. 26 (8). 30 October 2000. Retrieved 19 September 2015.
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- "2002 Genetics Prize: H. Robert Horvitz". Gruber prizes. The Gruber Foundation. Retrieved 20 May 2016.
- Altman, Lawrence K. (8 October 2002). "3 Win Nobel for Work on Suicidal Cells". The New York Times. Retrieved 19 September 2015.
- Badge, Peter; Turner, Nikolaus (2008). Nobel faces : a gallery of Nobel Prize winners. Weinheim [Germany]: Wiley-VCH. pp. 506–507. ISBN 9783527406784.
- Carey, Jr, Charles W. (2006). "Horvitz, H. Robert". American scientists. New York: Facts on File. pp. 179–180. ISBN 9781438108070.
- Drogin, Eric (2008). "Programmed cell death". Science for lawyers (1st ed.). Chicago, IL: American Bar Association. pp. 40–41. ISBN 9781590319260.
- Heemels, Marie-Thérèse (1 July 2004). "131 corpses and a Nobel prize". Nature Milestones. Nature Publishing Group. doi:10.1038/nrn1463. Retrieved 19 September 2015.
- Pelengaris, Stella; Khan, Mike. The Molecular Biology of Cancer: A Bridge from Bench to Bedside. pp. 269–270. ISBN 9781118430859.
- Stone, Nikki (2010). "Dr. H. Robert Horvitz". When turtles fly the secrets of successful people who know how to stick their necks out. New York: Morgan James. pp. 55–60. ISBN 9781600378010.