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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. 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).

Early life and education

Elledge was born in Paris, Illinois in 1956. 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.

He entered the University of Illinois Urbana-Champaign, majoring in chemistry and hoping to become an organic chemist. 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, which prompted him to study PhD in biology at the Massachusetts Institute of Technology (MIT) after obtaining his BSc in 1978. Elledge graduated from MIT in 1983.

Career

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

In 2003, Elledge joined the Department of Genetics of Harvard Medical School.

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. He also sits on the Board of Advisory Scientists of the Whitehead Institute and the advisory board of Molecular Cell.

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

Research

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 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. The human counterparts of RNR2, or homologs, are RRM2 and RRM2B.

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, MEC1, and TEL1 in yeasts, (respective human homologs are CHEK2, ATR, and ATM) and CHEK1 and CHEK2 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. He also showed that the Rb protein physically associates with PP1a from mitosis until mid-G1 phase in yeasts. 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.

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. He correctly predicted the central role of F-Box in protein degradation due to the large number of proteins having this motif.

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

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.

During the COVID-19 pandemic, Elledge estimated that United States has lost a total of 2.5 million years of life.

Personal life

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

Awards

• Paul Marks Prize for Cancer Research (2001)
• National Academy of Sciences Award in Molecular Biology (2002)
• Member of the National Academy of Sciences (2003)
• Member of the American Academy of Arts and Sciences (2003)
• Hans Sigrist Prize (2005)
• Genetics Society of America Medal (2005)
• Fellow of the American Academy of Microbiology (2005)
• Member of the Institute of Medicine) (now National Academy of Medicine) (2006)
• Dickson Prize (2010)
• Lewis S. Rosenstiel Award (2012)
• Canada Gairdner International Award (2013)
• Fellow of the American Association for Cancer Research Academy (2014)
• Albert Lasker Award for Basic Medical Research (2015)
• Breakthrough Prize in Life Sciences (2017)
• Gruber Prize in Genetics (2017)
• Alumni Award, University of Illinois Alumni Association (2017)
• Fellow of the American Association for the Advancement of Science (2018)

References

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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.
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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.
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External links

• His academic home page
• His Howard Hughes Medical Institute bio
• Elledge Lab Page

• Living people
• American geneticists
• American molecular biologists
• Howard Hughes Medical Investigators
• Members of the United States National Academy of Sciences
• Harvard Medical School faculty
• Baylor College of Medicine faculty
• Stanford University staff
• Massachusetts Institute of Technology School of Science alumni
• Recipients of the Albert Lasker Award for Basic Medical Research
• 1956 births
• Fellows of the AACR Academy
• Fellows of the American Academy of Arts and Sciences
• Fellows of the American Association for the Advancement of Science
• University of Illinois Urbana-Champaign alumni
• Members of the National Academy of Medicine
• Helen Hay Whitney Foundation fellows