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Stephen Elledge

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Stephen Joseph Elledge (born August 7, 1956) is an American geneticist. He is the current Gregor Mendel Professor of Genetics and of Medicine at the Department of Genetics of Harvard Medical School and in the Division of Genetics of the Brigham and Women's Hospital.[3][4] His research is focused on the genetic and molecular mechanisms of eukaryotic response to DNA damage and is known as the discoverer of the DNA damage response (DDR).

Stephen Joseph Elledge[1]
Born (1956-08-07) August 7, 1956 (age 68)[2]
Paris, Illinois[2]
NationalityAmerican
EducationUniversity of Illinois Urbana-Champaign (BSc)
Massachusetts Institute of Technology (PhD)
Known forCell cycle research
DNA repair research
SpouseMitzi Kuroda
AwardsNAS Award in Molecular Biology
Breakthrough Prize in Life Sciences
Genetics Society of America Medal
Dickson Prize
Canada Gairdner International Award
Albert Lasker Award for Basic Medical Research
Gruber Prize in Genetics
Scientific career
FieldsGenetics
Molecular biology
InstitutionsHarvard University
Brigham and Women's Hospital
Baylor College of Medicine
Howard Hughes Medical Institute
Stanford University
ThesisIdentification and characterization of genes involved in mutagenesis in Escherichia coli (1983)
Doctoral advisorGraham C. Walker

Early life and education

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Elledge was born in Paris, Illinois in 1956.[2] He also grew in up, graduating from Paris High School in 1974. He has been interested in chemistry since childhood, thanks to a chemistry set his grandmother gave him.[5]

He entered the University of Illinois Urbana-Champaign, majoring in chemistry and hoping to become an organic chemist.[6] Elledge initially ignored life science subjects, until he attended biology and genetics courses on exchange to the University of Southampton, England, during his third (or junior) year. He took biochemistry courses after returning to Illinois,[7] which prompted him to study PhD in biology at the Massachusetts Institute of Technology (MIT) after obtaining his BSc in 1978.[8] Elledge graduated from MIT in 1983.[2]

Career

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Elledge started his career as a postdoctoral fellow at Stanford University in 1984 in Ronald W. Davis's group.[8] In 1989, he moved to the Baylor College of Medicine as an assistant professor in biochemistry,[9] He was promoted to associate professor in 1993 and full professor in 1995.[2]

In 2003, Elledge joined the Department of Genetics of Harvard Medical School.[10][11]

Currently, Elledge is the Gregor Mendel Professor of Genetics and of Medicine at the Department of Genetics of Harvard Medical School and in the Division of Genetics of the Brigham and Women's Hospital.[3][12] He also sits on the Board of Advisory Scientists of the Whitehead Institute[13] and the advisory board of Molecular Cell.[14]

Elledge has been an investigator at the Howard Hughes Medical Institute since 1993.[15]

Research

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Elledge's research spans multiple areas, including cell cycle, DNA repair, and detection of virus from blood.

He began studying DNA repair during his years at Stanford University as a postdoctoral fellow. Elledge accidentally[16] discovered the RNR2 gene and protein in yeast, which belongs to the family of ribonucleotide reductase, and found that its expression increases when DNA is damaged.[17] The human counterparts of RNR2, or homologs, are RRM2 and RRM2B.[18]

Over the next decade, he continued the search for genes and proteins involved in the DNA damage response pathway in yeasts and humans. Examples include DUN1,[19] MEC1, and TEL1 in yeasts,[20] (respective human homologs are CHEK2, ATR, and ATM) and CHEK1[21] and CHEK2[22] in humans.

In cell cycle research, his group published two important papers on cell cycle checkpoints in 1993. In parallel and independently from Bert Vogelstein's group, he discovered and characterized p21, a cyclin-dependent kinase inhibitor protein that blocks G1/S transition.[23] He also showed that the Rb protein physically associates with PP1a from mitosis until mid-G1 phase in yeasts.[24] After moving to the Baylor College of Medicine, Elledge reported his identification of CDK2, a protein whose activation allows cells to transit from the G1 phase into the S phase of the cell cycle.[25]

Elledge's group also discovered the F-box protein structural motif, and found that it recognizes specific protein sequences and tags the proteins with ubiquitin for degradation.[26] He correctly predicted the central role of F-Box in protein degradation due to the large number of proteins having this motif.[27]

In 2015, Elledge's group developed VirScan, a platform that detects viral infection in patients from a small amount of blood.[28][29][30]

In recent years, Elledge has continued to expand his research area. For instance, his group reported a computational model that predicted the likelihood of regions on the chromosome to be abnormally amplified.[31][32]

During the COVID-19 pandemic, Elledge estimated that United States has lost a total of 2.5 million years of life.[33][34][35][36]

Personal life

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Elledge was married to Mitzi Kuroda,[37] herself a professor at the Department of Genetics at Harvard Medical School.[38] They both moved from Baylor College of Medicine to Harvard Medical School in 2003.[39]

Awards

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References

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  1. ^ a b "Stephen Joseph Elledge". Gairdner Foundation. Archived from the original on May 28, 2022. Retrieved May 28, 2022.
  2. ^ a b c d e "Oral history interview with Stephen J. Elledge". Science History Institute. August 18, 1995. Archived from the original on March 15, 2023. Retrieved March 15, 2023.
  3. ^ a b "Stephen J. Elledge, Ph.D". Harvard Medical School. February 10, 2023. Archived from the original on March 21, 2023. Retrieved March 21, 2023.
  4. ^ "People". Harvard Medical School. Archived from the original on March 17, 2023. Retrieved March 17, 2023.
  5. ^ Loughlin, Sue (December 23, 2016). "Wabash Valley native honored for pioneering research". Tribune-Star. Archived from the original on March 16, 2023. Retrieved March 16, 2023.
  6. ^ Nadis, Steve. "A Drop of Blood, a History of Viruses". Discover. Archived from the original on December 12, 2016. Retrieved December 16, 2016.
  7. ^ Howard, Joy. "Stephen J. Elledge, PhD". Brigham Health. No. Summer 2017. Brigham and Women’s Hospital. Archived from the original on March 25, 2023. Retrieved March 25, 2023.
  8. ^ a b Brownlee, Christen (2004). "Biography of Stephen J. Elledge". Proceedings of the National Academy of Sciences. 101 (10): 3336–3337. doi:10.1073/pnas.0400868101. PMC 373462. PMID 14993590.
  9. ^ Rogers, Kara (August 3, 2022). "Stephen J. Elledge". Encyclopædia Britannica. Retrieved March 23, 2023.
  10. ^ Azvolinsky, Anna (September 30, 2017). "Damage Patroller". The Scientist. No. October 2017. Archived from the original on July 26, 2020. Retrieved July 26, 2020.
  11. ^ Peterson, Doug (November 1, 2013). "A Molecular Pathfinder". College of Liberal Arts & Sciences, University of Illinois Urbana-Champaign. Archived from the original on August 9, 2022. Retrieved August 9, 2022.
  12. ^ "Genetics Researchers & Staff". Brigham and Women's Hospital. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  13. ^ "Board of Advisory Scientists". Whitehead Institute. Archived from the original on March 27, 2023. Retrieved March 27, 2023.
  14. ^ "Advisory board". Molecular Cell. Archived from the original on March 27, 2023. Retrieved March 27, 2023.
  15. ^ "Stephen J. Elledge, PhD". Howard Hughes Medical Institute. Archived from the original on March 15, 2023. Retrieved March 15, 2023.
  16. ^ Elledge, Stephen J. (2015). "Accidents and Damage Control". Cell. 162 (6): 1196–1200. doi:10.1016/j.cell.2015.08.042. PMID 26359977.
  17. ^ Elledge, S. J.; Davis, R. W. (1987). "Identification and isolation of the gene encoding the small subunit of ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-inducible gene required for mitotic viability". Molecular and Cellular Biology. 7 (8): 2783–2793. doi:10.1128/mcb.7.8.2783-2793.1987. PMC 367895. PMID 3313004.
  18. ^ "RNR2 ribonucleotide-diphosphate reductase subunit RNR2 [ Saccharomyces cerevisiae S288C ]". National Center for Biotechnology Information. March 10, 2023. Archived from the original on March 29, 2023. Retrieved March 29, 2023.
  19. ^ Zhou, Zheng; Elledge, Stephen J. (1993). "DUN1 encodes a protein kinase that controls the DNA damage response in yeast". Cell. 75 (6): 1119–1127. doi:10.1016/0092-8674(93)90321-g. PMID 8261511. S2CID 6606697. Retrieved April 3, 2023.
  20. ^ Sanchez, Yolanda; Desany, Brian A.; Jones, William J.; Liu, Qinghua; Wang, Bin; Elledge, Stephen J. (1996). "Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways". Science. 271 (5247): 357–360. Bibcode:1996Sci...271..357S. doi:10.1126/science.271.5247.357. PMID 8553072. S2CID 21223989. Retrieved April 3, 2023.
  21. ^ Sanchez, Yolanda; Wong, Calvin; Thoma, Richard S.; Richman, Ron; Wu, Zhiqi; Piwnica-Worms, Helen; Elledge, Stephen J. (1997). "Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25". Science. 277 (5331): 1497–1501. doi:10.1126/science.277.5331.1497. PMID 9278511. Retrieved April 3, 2023.
  22. ^ Matsuoka, Shuhei; Huang, Mingxia; Elledge, Stephen J. (1998). "Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase". Science. 282 (5395): 1893–1897. Bibcode:1998Sci...282.1893M. doi:10.1126/science.282.5395.1893. PMID 9836640. Retrieved April 3, 2023.
  23. ^ Harper, J. Wade; Adami, Guy R.; Wei, Nan; Keyomarsi, Khandan; Elledge, Stephen J. (1993). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases" (PDF). Cell. 75 (4): 805–816. doi:10.1016/0092-8674(93)90499-g. PMID 8242751. S2CID 13614794. Archived from the original (PDF) on April 1, 2023. Retrieved April 1, 2023.
  24. ^ Durfee, Tim; Becherer, Kathleen; Chen, Phang-Lang; Yeh, Shiou-Hwei; Yang, Yanzhu; Kilburn, April E.; Lee, Wen-Hwa; Elledge, Stephen J. (1993). "The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit" (PDF). Genes & Development. 7 (9): 555–569. doi:10.1101/gad.7.4.555. PMID 8384581. S2CID 23631016. Archived from the original (PDF) on April 1, 2023. Retrieved April 1, 2023.
  25. ^ Elledge, S.J.; Spottswood, M.R. (1991). "A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1". EMBO Journal. 10 (9): 2653–2659. doi:10.1002/j.1460-2075.1991.tb07808.x. PMC 452966. PMID 1714386.
  26. ^ Bai, Chang; Sen, Partha; Hofmann, Kay; Ma, Lei; Goebl, Mark; Harper, J. Wade; Elledge, Stephen J. (1996). "SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box". Cell. 86 (2): 263–274. doi:10.1016/s0092-8674(00)80098-7. PMID 8706131.
  27. ^ Kipreos, Edward T.; Pagano, Michele (2000). "The F-box protein family". Genome Biology. 1 (5): reviews3002.1. doi:10.1186/gb-2000-1-5-reviews3002. PMC 138887. PMID 11178263.
  28. ^ Xu, George J.; Kula, Tomasz; Xu, Qikai; Li, Mamie Z.; Vernon, Suzanne D.; Ndung’u, Thumbi; Ruxrungtham, Kiat; Sanchez, Jorge; Brander, Christian; Chung, Raymond T.; O’Connor, Kevin C.; Walker, Bruce; Larman, H. Benjamin; Elledge, Stephen J. (2015). "Comprehensive serological profiling of human populations using a synthetic human virome". Science. 348 (6299): aaa0698. doi:10.1126/science.aaa0698. PMC 4844011. PMID 26045439.
  29. ^ Abbas, Anzar. "A Test Tells the Tale". HHMI Bulletin. Vol. 28, no. 3. Howard Hughes Medical Institute. Archived from the original on April 3, 2023. Retrieved April 5, 2023.
  30. ^ Bridger, Haley (June 4, 2015). "Viral History in a Drop of Blood". Harvard Medical School. Archived from the original on April 5, 2023. Retrieved April 5, 2023.
  31. ^ Davoli, Teresa; Xu, Andrew Wei; Mengwasser, Kristen E.; Sack, Laura M.; Yoon, John C.; Park, Peter J.; Elledge, Stephen J. (2013). "Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome". Cell. 155 (4): 948–962. doi:10.1016/j.cell.2013.10.011. PMC 3891052. PMID 24183448.
  32. ^ Null (January 30, 2017). "Interview with 2017 Breakthrough Prize winner Steve Elledge". Proceedings of the National Academy of Sciences. Archived from the original on April 6, 2023. Retrieved April 6, 2023.
  33. ^ Elledge, Stephen J. (October 27, 2020). "2.5 Million Person-Years of Life Have Been Lost Due to COVID-19 in the United States". medRxiv 10.1101/2020.10.18.20214783.
  34. ^ Weintraub, Karen (October 20, 2020). "The 'shocking' impact of COVID-19: Americans, young and old, have lost 2.5 million years of life, Harvard researcher says". USA Today. Archived from the original on March 25, 2023. Retrieved March 23, 2023.
  35. ^ Deese, Kaelan (October 21, 2020). "Harvard researcher estimates COVID-19 has cost US 2.5 million years of life". The Hill. Archived from the original on March 25, 2023. Retrieved March 23, 2023.
  36. ^ Wu, Katherine J. (October 21, 2020). "The Coronavirus Has Claimed 2.5 Million Years of Potential Life in the U.S., Study Finds". The New York Times. Archived from the original on December 31, 2022. Retrieved December 31, 2022.
  37. ^ a b "Stephen Elledge". Gruber Foundation. Archived from the original on March 17, 2023. Retrieved March 17, 2023.
  38. ^ "Mitzi I. Kuroda, Ph.D." Department of Genetics, Harvard Medical School. November 2021. Archived from the original on March 17, 2023. Retrieved March 17, 2023.
  39. ^ "Movers". Nature. 423 (6938): 464. 2003. Bibcode:2003Natur.423..464.. doi:10.1038/nj6938-464a.
  40. ^ "2001 Prize Winners". Memorial Sloan Kettering Cancer Center. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  41. ^ "NAS Award in Molecular Biology". National Academy of Sciences. Archived from the original on March 18, 2023. Retrieved March 18, 2023.
  42. ^ "Stephen J. Elledge". National Academy of Sciences. Archived from the original on March 18, 2023. Retrieved March 18, 2023.
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  44. ^ "Hans Sigrist Prize Winners". Hans Sigrist Foundation. October 15, 2021. Archived from the original on March 14, 2023. Retrieved March 14, 2023.
  45. ^ Haber, James E. (2005). "The 2005 Genetics Society of America Medal". Genetics. 169 (2): 506–507. doi:10.1093/genetics/169.2.506. PMC 1449134. PMID 15731513. Archived from the original on March 18, 2023. Retrieved March 18, 2023.
  46. ^ a b "Stephen J. Elledge, PhD". American Association for Cancer Research. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  47. ^ "Stephen J. Elledge, Ph.D." National Academy of Medicine. Archived from the original on March 20, 2023. Retrieved March 20, 2023.
  48. ^ "2010 Dickson Prize Winner". Dickson Prize in Medicine. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  49. ^ "Past Winners". Brandeis University. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  50. ^ "2015 Albert Lasker Basic Medical Research Award". Lasker Award. Archived from the original on March 19, 2023. Retrieved March 19, 2023.
  51. ^ "Stephen J. Elledge". Breakthrough Prize. Archived from the original on March 17, 2023. Retrieved March 17, 2023.
  52. ^ "2017 Alumni Award recipient, Stephen Elledge, '78 LAS". University of Illinois Alumni Association. June 22, 2017. Archived from the original on March 23, 2023. Retrieved March 23, 2023.
  53. ^ "Elected Fellows". American Association for the Advancement of Science. Archived from the original on March 20, 2023. Retrieved March 20, 2023.
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