SPEAKERS
William G. Kaelin, Jr.
AFFILIATION:
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
POSITION TITLE:
Professor, Medicine, Harvard Medical School
Senior Physician, Medicine, Brigham And Women's Hospital
EDUCATION/TRAINING:
| Duke University, Durham, NC | B.A. 1979 | Mathematics |
| Duke University, Durham, NC | B.A. 1979 | Chemistry |
| Duke University Medical School, Durham, NC | M.D. 1982 | Medicine |
HONORS:
1978 Phi Beta Kappa
1979 Julia Dale Award in Mathematics
1979 Summa Cum Laude
1983 Alpha Omega Alpha
1993 James S. McDonnell Scholar Award
2001 The Paul Marks Prize, Memorial Sloan Kettering Cancer Center
2002 Elected Member, The Johns Hopkins Society of Scholars
2006 Richard and Hinda Rosenthal Foundation Award, AACR
2006 Doris Duke Distinguished Clinical Investigator Award
2007 Duke University School of Medicine Distinguished Alumni Award
2007 Elected to Institute of Medicine
2008 AICR Colin Thomson Medal
2010 Canada Gairdner Award
2010 Member, National Academy of Sciences, USA
2011 Alfred Knudson Award in Cancer Genetics
2012 Stanley J. Korsmeyer Award, ASCI
2012 Elected to Association of American Physicians
2012 Scientific Grand Prix of the Foundation Lefoulon-Delalande
2014 Wiley Prize in Biomedical Sciences
2014 Elected Fellow, AACR Academy
2014 Steven C. Beering Award, Indiana University School of Medicine
2016 Princess Takamatsu Award, American Association for Cancer Research
2016 Science of Oncology Award, American Society of Clinical Oncology
2016 Albert Lasker Basic Medical Research Award
2017 Katharine Berkan Judd Award Lectureship, Memorial Sloan Kettering Cancer Center
2018 Helis Foundation Award
2018 Endowed Chair, Sidney Farber Professor of Medicine
2018 Massry Prize
2019 Nobel Prize in Physiology or Medicine
2020 Elected to American Academy of Arts and Sciences
RESEARCH INTERESTS:
My Laboratory uses biochemical, cell-based, and animal-based assays to gain mechanistic insights into how cancer-relevant proteins, such pRB and pVHL, regulate tumor growth. For example, our pVHL work showed that deregulation of HIF2, and HIF-target genes such as VEGF, plays a critical role in kidney cancer. This information motivated the successful clinical testing of VEGF inhibitors for this disease. In the course of these studies, we also discovered how the stability of HIF (hypoxia-inducible factor) is coupled to oxygen availability. Specifically, we showed that the HIF subunit of the HIF heterodimer undergoes an oxygen-dependent posttranslational modification, prolyl hydroxylation, which targets it for polyubiquitylation by pVHL and subsequent proteasomal degradation. This modification is catalyzed by members of the EglN (also called PHD) family of 2-oxoglutarate (2-OG)-dependent dioxygenases. Most recently we applied our knowledge of 2-OG-dependent dioxygenases to the study of tumor-derived IDH mutants, which overproduce 2-hydroxyglutarate (2-HG). We have helped to identify pathogenic targets of 2-HG and also showed that the effects of 2-HG on leukemic transformation are reversible in preclinical models. This helped motivate the development of drugs that block 2-HG production by mutant IDH1 and IDH2. Such drugs appear promising in early clinical trials. Leveraging our prior work related to ubiquitin ligases, we discovered that thalidomide-like drugs alter the substrate specificity of the cereblon ubiquitin ligase such that it now destroys IKZF1 and IKZF3, which act as lineage-addiction oncogenes in multiple myeloma. Finally, I have had a longstanding interest in the pRB tumor suppressor protein and cloned one of its targets, E2F1, as a postdoctoral fellow. We showed that another pRB target, RBP2 (KDM5A), is a histone demethylase and promotes tumor formation in pRB-defective cells.
PUBLICATIONS:
Complete List of Published Work in MyBibiolography: