William G. Kaelin, Jr., MD
Professor of Medicine
Howard Hughes Medical Institute
Dana-Farber Cancer Institute
Harvard Medical School
2013-2014 BCRF Project:
A protein called Cyclin D1 stimulates breast cancer cells to proliferate, so having new ways to turn Cyclin D1 off would provide an advantage in the developmen of new cancer therapies. Dr. Kaelin discovered that inhibiting another protein, called EglN2, lowers Cyclin D1 levels in breast cancer cells and blocks their proliferation. EglN2 is an ""enzyme,"" meaning that EglN2 accelerates a specific chemical reaction in cells. As is often true for enzymes, EglN2 can be inhibited with chemicals that have the right properties to be used as drugs. Dr. Kaelin's team also discovered that EglN2 chemically modifies a protein called FOXO3A in a way that causes FOXO3A to be unstable. Loss of EglN2 allows FOXO3A to accumulate and to suppress the production of Cyclin D1. These discoveries in sum have identified a potential new way to attack breast cancer cells (inhibit EglN2), as well as the mechanism by which EglN2 regulates breast cancer proliferation.
In 2013-2014, Dr. Kaelin plans to build on these discoveries, as well as shift the focus to his group’s other findings that some breast cancer cells secrete a chemical called glutamate, which causes neighboring cancer cells to be more aggressive. This suggests that blocking the production of glutamate, or its ability to signal to neighboring cells, might be a useful adjunct for breast cancer treatment.
Dr. William G. Kaelin, Jr. obtained his undergraduate and medical degrees from Duke University and completed his training in internal medicine at the Johns Hopkins Hospital, where he served as chief medical resident. He was a clinical fellow in medical oncology at the Dana-Farber Cancer Institute and later a postdoctoral fellow in the laboratory of fellow BCRF grantee, Dr. David Livingston, during which time he was a McDonnell Scholar. He is currently a Professor in the Department of Medicine at the Dana-Farber Cancer Institute and the Brigham and Women's Hospital, Harvard Medical School. He is the Associate Director, Basic Science, for the Dana-Farber/Harvard Cancer Center and Chair of the Executive Committee for Research for the Dana-Farber Cancer Institute.
Dr. Kaelin is a member of the American Society of Clinical Investigation and the American College of Physicians. He recently served on the National Cancer Institute Board of Scientific Advisors, the American Association for Cancer Research (AACR) Board of Trustees, and the Institute of Medicine National Cancer Policy Board. He is a recipient of the Paul Marks Prize for cancer research from the Memorial Sloan-Kettering Cancer Center, the Richard and Hinda Rosenthal Prize from the AACR, and a Doris Duke Distinguished Clinical Scientist award. In 2007, Dr. Kaelin was elected to the Institute of Medicine. In 2010, Dr. Kaelin was elected to the National Academy of Sciences and was a recipient of the 2010 Canada International Gairdner Award. In 2012, he was a co-recipient of both the Stanley J. Korsmeyer Award from the American Society of Clinical Investigation (ASCI) and the Scientific Grand Prix of the Foundation Lefoulon-Delalande and the Institute of France.