Skip Navigation

William G. Kaelin Jr., MD


Researcher


Researcher

  • Sidney Farber Professor of Medicine, Harvard Medical School
  • Investigator, Howard Hughes Medical Institute

Contact Information

  • Office Phone Number617-632-3975
  • Fax617-632-4760

Bio

Dr. Kaelin received his MD from Duke University in 1982 and was a house officer and chief resident in internal medicine at Johns Hopkins Hospital. He was a medical oncology clinical fellow at Dana-Farber and a postdoctoral fellow in the laboratory of Dr. David Livingston, where he began his studies of tumor suppressor proteins. He became an independent investigator at Dana-Farber in 1992, and a Howard Hughes Medical Institute Investigator and Professor of Medicine at Harvard Medical School in 2002.

Recent Awards:

  • Science of Oncology Award, ASCO 2016
  • Canada Gairdner International Award 2010
  • Elected to National Academy of Sciences 2010
  • Alfred Knudson Award in Cancer Genetics, NCI 2011
  • Stanley J. Korsmeyer Award, ASCI 2012
  • Scientific Grand Prix, Foundation Lefoulon-Delalande 2012
  • Wiley Prize in Biomedical Sciences 2014
  • AICR Colin Thomson Medal 2008
  • Elected to Institute of Medicine 2007
  • Duke University School of Medicine Distinguished Alumni Award 2007
  • Doris Duke Distinguished Clinical Investigator Award 2006
  • Richard and Hinda Rosenthal Foundation Award, AACR 2006
  • Elected to Johns Hopkins Society of Scholars 2003
  • Paul Marks Prize, Memorial Sloan Kettering Cancer Center 2001
  • James S. McDonnell Scholar Award 1993
  • NIH Physician-Scientist Award 1990
  • NIH National Research Service Award 1990
  • Alpha Omega Alpha Medical Honor Society 1983
  • Phi Beta Kappa 1978
  • AACR Academy 2014
  • Steven C. Beering Award 2014
  • The Princess Takamatsu Award, AACR 2016

Research

Functions of Tumor Suppressor Proteins

Our laboratory studies tumor suppressor genes and the normal functions of the proteins they encode. The long-term goal of this work is to lay the foundation for the development of new anticancer therapies based on the functions of specific tumor suppressor proteins. For example, it may be possible to develop a drug that mimics the behavior of a certain tumor suppressor protein, or to design strategies for killing only those cells in which a particular tumor suppressor protein has been inactivated, thus sparing normal cells.We are currently concentrating on the von Hippel-Lindau tumor suppressor protein (pVHL), the retinoblastoma tumor suppressor protein (pRB), and the p53-like protein p73. pVHL inactivation is common in several cancers including clear cell renal carcinoma. Our laboratory established that when oxygen is available, pVHL targets for destruction another protein called hypoxia-inducible factor (HIF). Cells lacking pVHL, or starved of oxygen, accumulate HIF, which activates a cadre of genes that facilitate adaptation to hypoxia. We showed that downregulation of HIF is both necessary and sufficient for pVHL to suppress the growth of renal carcinomas in experimental models. This work motivated clinical trials of agents that inhibit HIF-responsive growth factors such as vascular endothelial growth factor (VEGF). At least one VEGF inhibitor will likely be approved for the treatment of renal carcinoma in 2005.Earlier work by our group showed that the binding of pVHL to HIF requires that HIF be hydroxylated on one of two proline residues. Preclinical data suggest that preventing this modification pharmacologically might be useful for the treatment of diseases characterized by impaired oxygen delivery, including myocardial infarctions and strokes. In other research, we are studying tuberous sclerosis, a hereditary cancer syndrome caused by mutations of either the TSC1 or TSC2 genes. We recently discovered that TSC1 and TSC2, like pVHL, regulate HIF; we also found that another protein, REDD1, plays an important role in adaptation to chronic hypoxia by modulating the function of TSC1 and TSC2. The best understood function of the pRB protein is its ability to inhibit the E2F transcription factor. We discovered that pRB interacts with another protein, RBP2, which also has features of a transcription factor. Importantly, we showed that inhibition of RBP2 in cells lacking pRB induces some of the same changes observed following restoration of pRB function, including the induction of differentiation. We are now studying the biochemistry of RBP2 in greater detail.

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
Mayer 457
Boston, MA 02215
Get Directions

Top