William G. Kaelin, Jr., MD

2012-2013 BCRF Project:
With BCRF support, the Kaelin laboratory has shown that breast cancers, especially those that depend on the hormone estrogen, need a protein called EglN2 to grow. EglN2 is an "enzyme," meaning that it can accelerate a particular chemical reaction in the cell. This is important because enzymes often make good drug targets. The Kaelin laboratory has used BCRF funding to learn more about the chemical reaction that is regulated by EglN2 and to see if other enzymes related to EglN2 are also important in breast cancer development. The researchers are also using recently developed tools to determine which of these enzymes, when inhibited, can suppress breast cancer growth. They showed that EglN2 controls breast cancer cell proliferation, and they also have evidence that enzymes related to EglN2 are deregulated in triple negative breast cancer. Dr. Kaelin's work may lead to the development of an entirely new class of drugs for the treatment of breast cancer.

In 2012-2013, Dr. Kaelin's team will determine how EglN2 regulates Cyclin D1, a protein that controls components of the cell cycle. They will also look at the role of histone demethylases in breast cancer proliferation. In addition, they will look at the relationship between hypoxia, the deprivation of oxygen during cell growth and development, in the formation of triple negative breast cancer.

Mid-year Progress: Dr. Kaelin's laboratory continues to examine how, mechanistically, EglN2 regulates breast cancer growth. They are asking the question if other proteins closely related to EglN2, including some that influence how DNA is "packaged" in the cell, are important for breast cancers. Finally, they have recently discovered a new way that breast cancer cells communicate with one another to promote tumor growth and metastasis.

Bio:
Dr. Kaelin is a Professor in the Department of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School, and Associate Director, Basic Science, for the Dana-Farber/Harvard Cancer Center. He 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, during which time he was a McDonnell Scholar.

Dr. Kaelin is a member of the American Society of Clinical Investigation, the Institute of Medicine (IOM), and the National Academy of Sciences. He recently served on the National Cancer Institute Board of Scientific Advisors and the IOM 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, the Canada Gairdner International Prize, the Alfred Knudson Lecture in Cancer Genetics award, ASCI’s Stanley Korsmeyer Award and the Scientific Grand Prix of the Foundation Lefoulon-Delalande.

A Howard Hughes Medical Investigator since 1998, Dr. Kaelin seeks to understand how, mechanistically, mutations affecting tumor-suppressor genes cause cancer and to use that information to develop better anticancer agents. His work on the VHL tumor suppressor protein led to new insights into how cells sense and respond to changes in oxygen, and thus has implications for diseases beyond cancer, such as myocardial infarction and stroke.