Stephen Joseph Elledge [1] | |
---|---|
Born | [2] | August 7, 1956
Nationality | American |
Education | University of Illinois Urbana-Champaign (BSc) Massachusetts Institute of Technology (PhD) |
Known for | Cell cycle research DNA repair research |
Spouse | Mitzi Kuroda |
Awards | NAS 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 | |
Fields | Genetics Molecular biology |
Institutions | Harvard University Brigham and Women's Hospital Baylor College of Medicine Howard Hughes Medical Institute Stanford University |
Thesis | Identification and characterization of genes involved in mutagenesis in Escherichia coli (1983) |
Doctoral advisor | Graham C. Walker |
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).
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]
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]
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]
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]
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.
Susan Lee Lindquist, ForMemRS was an American professor of biology at MIT specializing in molecular biology, particularly the protein folding problem within a family of molecules known as heat-shock proteins, and prions. Lindquist was a member and former director of the Whitehead Institute and was awarded the National Medal of Science in 2010.
Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs.
Leland Harrison (Lee) Hartwell is former president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington. He shared the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Tim Hunt, for their discoveries of protein molecules that control the division (duplication) of cells.
Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase, is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribose ring of nucleoside diphosphates. This reduction produces deoxyribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms. Furthermore, RNR plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. A somewhat unusual feature of the RNR enzyme is that it catalyzes a reaction that proceeds via a free radical mechanism of action. The substrates for RNR are ADP, GDP, CDP and UDP. dTDP is synthesized by another enzyme from dTMP.
Charles David Allis was an American molecular biologist, and the Joy and Jack Fishman Professor at the Rockefeller University. He was also the Head of the Laboratory of Chromatin Biology and Epigenetics, and a professor at the Tri-Institutional MD–PhD Program.
The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas.
Evelyn M. Witkin was an American bacterial geneticist at Cold Spring Harbor Laboratory (1944–1955), SUNY Downstate Medical Center (1955–1971), and Rutgers University (1971–1991). Witkin was considered innovative and inspirational as a scientist, teacher and mentor.
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates ; phosphorylation of these proteins leads to cell cycle progression.
Arthur L. Horwich is an American biologist and Sterling Professor of Genetics and Pediatrics at the Yale School of Medicine. Horwich has also been a Howard Hughes Medical Institute investigator since 1990. His research into protein folding uncovered the action of chaperonins, protein complexes that assist the folding of other proteins; Horwich first published this work in 1989.
Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the MRE11 gene. The gene has been designated MRE11A to distinguish it from the pseudogene MRE11B that is nowadays named MRE11P1.
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.
Angelika Amon was an Austrian American molecular and cell biologist, and the Kathleen and Curtis Marble Professor in Cancer Research at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, United States. Amon's research centered on how chromosomes are regulated, duplicated, and partitioned in the cell cycle. Amon was elected to the American Academy of Arts and Sciences in 2017.
Lewis C. Cantley is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.
Bruce William Stillman is a biochemist and cancer researcher who has served as the Director of Cold Spring Harbor Laboratory (CSHL) since 1994 and President since 2003. He also served as the Director of its NCI-designated Cancer Center for 25 years from 1992 to 2016. During his leadership, CSHL has been ranked as the No. 1 institution in molecular biology and genetics research by Thomson Reuters. Stillman's research focuses on how chromosomes are duplicated in human cells and in yeast Saccharomyces cerevisiae; the mechanisms that ensure accurate inheritance of genetic material from one generation to the next; and how missteps in this process lead to cancer. For his accomplishments, Stillman has received numerous awards, including the Alfred P. Sloan, Jr. Prize in 2004 and the 2010 Louisa Gross Horwitz Prize, both of which he shared with Thomas J. Kelly of Memorial Sloan-Kettering Cancer Center, as well as the 2019 Canada Gairdner International Award for biomedical research, which he shared with John Diffley.
Stephen C. Harrison is professor of biological chemistry and molecular pharmacology, professor of pediatrics, and director of the Center for Molecular and Cellular Dynamics of Harvard Medical School, head of the Laboratory of Molecular Medicine at Boston Children's Hospital, and investigator of the Howard Hughes Medical Institute.
Michael Nip Hall is an American-Swiss molecular biologist and professor at the Biozentrum of the University of Basel, Switzerland. He discovered TOR, a protein central for regulating cell growth.
Sir Stephen Philip Jackson, FRS, FMedSci is the Frederick James Quick Professor of Biology. He is a senior group leader at the Cancer Research UK Cambridge Institute and associate group leader at the Gurdon Institute, University of Cambridge.
Joseph Heitman is an American physician-scientist focused on research in genetics, microbiology, and infectious diseases. He is the James B. Duke Professor and Chair of the Department of Molecular Genetics and Microbiology at Duke University School of Medicine.
Marian Bille Carlson is a geneticist and the Director of Life Sciences at the Simons Foundation. She is a member of the National Academy of Sciences and a past president of the Genetics Society of America.