2015 Collaborative Research Development Grant Recipient — Michael Yaffe, MD, PhD

Project Summary

Ovarian cancer is the fifth deadliest cancer among women in the United States. In spite of advances in surgery and drug therapy over the past several decades, cure rates remain very low (~30%). Most women are diagnosed with late-stage ovarian disease and, of these, a majority will die of drug-resistant disease within five years. Thus, treatment strategies that improve the potency and selectivity of current chemotherapy have the potential to make a dramatic impact on patient outcomes for this deadly disease. Recently, our laboratory identified a gene called MK2 that sends and receives signals within cancer cells, preventing them from dying when treated with chemotherapy. When we block MK2, we found that we could improve the ability of the chemotherapy to kill cancer cells by several fold, while leaving normal healthy cells unaffected. However, drugs that are capable of blocking MK2 in cancer cells are currently not available. Our research supported by the Ovarian Cancer Research Fund aims to develop ‘smart’ drug delivery vehicles that are capable of delivering a two-component therapy to cancer cells. The first component will be an MK2 blocking agent, which will increase the sensitivity of the cancer cells to currently used chemotherapy which forms the second component of our ‘smart’ drugs. We will use patient-based mouse avatars to model human disease response, and leverage new advances in the development of nanometer-scale drug delivery technologies that are both biocompatible and highly targeted towards ovarian cancer cells. These studies will not only improve our understanding ovarian cancer sensitivity towards current therapy, but also develop strategies that can make a profound impact on patients with this devastating disease.

Co-investigator

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Paula T. Hammond, PhD – Massachusetts Institute of Technology

Bio

Michael B. Yaffe, M.D., Ph.D., is the David H. Koch Professor of Biological Engineering and Biology at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. He is also a senior associate member of the Broad Institute, and an Attending Surgeon/Surgical Intensivist in the Departments of Surgery and Anesthesia at Beth Israel Deaconess Medical Center, Harvard Medical School.

Dr. Yaffe received his B.S. in Materials Science and Engineering from Cornell University, and his M.D. and Ph.D. degrees from Case Western Reserve University, followed by advanced post-doctoral training with Prof. Lew Cantley in the Dept. of Cell Biology at Harvard Medical School. Dr. Yaffe’s research focuses on signaling pathways that cells use to respond to injury and inflammation, particularly the role of protein kinases and modular protein domains in the DNA damage response, tumor development, and anti-cancer therapeutics. His laboratory uses a highly multi-disciplinary approach that connects systems biology and bio-computation with molecular pharmacology, biochemistry/proteomics, and cell and structural biology. Recent work in his laboratory has led to new therapeutic approaches for the treatment of triple negative breast cancer, lung cancer, and ovarian cancer by employing traditional anti-cancer agents in very unconventional ways. Ongoing work continues to explore how inhibition of specific signaling pathways can be used to improve the response of tumors to combination chemotherapy and chemo-radiation treatment.

Dr. Yaffe is also the Scientific Editor-in-Chief of Science Signaling, a member of the Editorial Boards of Molecular and Cellular Proteomics, and Cell Cycle, and a Lieutenant Colonel in the U.S. Army Reserve Medical Corps.