A distinguished leader and innovator, Dr. Sharpless is known for his seminal studies of the relationship between tumor suppressor activation, cell cycle control, cellular senescence and molecular aging. By tracking expression of the p16INK4 (or CDKN2a) tumor suppressor in human tissues, Dr. Sharpless demonstrated that p16INK4a activation represents a key biomarker and effector of cellular aging. Dr. Sharpless is further credited with engineering the p16LUC knock-in mouse model, which allows for in vivo visualization of p16INK4a activation, showing that activation of this tumor suppressor is a common early event in both the malignant and stromal compartments of nascent tumors. Based on his work, the p16INK4a biomarker has become one of the most commonly used in vivo tools to mark senescent cells, whose depletion by genetic means ( ‘senolysis’) in murine models leads to the amelioration of age-associated pathologies and lifespan extension.
His work has also contributed to the understanding of cellular senescence in the context of tumorigenesis. He has demonstrated a connection between the failure of discrete stem cell compartments to senesce, resulting in cancer onset, and providing mechanistic insights into the process of spontaneous tumorigenesis. More recently, he has uncovered that chemotherapy treatment can induce pro-inflammatory senescence in both murine models and human patients, and has proposed the measure of the burden of senescent cells in vivo as a means to quantify physiological age. This idea has led to a biomarker of molecular aging that has been tested as a predictor of age-associated toxicity from various types of therapy in over 1,000 human patients with cancer and non-malignant disease.
He also developed the use of cyclin-dependent kinase inhibitors to induce transient inhibition of proliferation in somatic and progenitor cell compartments, thereby rendering these cells resistant to DNA damaging agents such as cytotoxic chemotherapy and ionizing radiation. This concept of “pharmacological quiescence” has since been employed to produce robust protection of the bone marrow in mammalian models and patients receiving DNA damaging agents as therapy for cancer. In addition to his research efforts, Dr. Sharpless is a visionary entrepreneur, having founded two clinical stage biotechnology companies that aim to reduce the burden of suffering in patients with cancer. Notably, and most recently in October of 2017, the President appointed him the 15th Director of the National Cancer Institute.
2016-2019 Board of Directors, Association of American Cancer Institutes, Pittsburgh, Pennsylvania
2016 Elected Councilor, National Institutes of Aging, Baltimore, Maryland
2014 Elected Member, Association of American Physicians, Belleville, Michigan
2011-2014 Elected Councilor, American Society for Clinical Investigation, Ann Arbor, Michigan
2010 Glenn Award for Research in Biological Mechanisms of Aging, Glenn Foundation for Medical Research, Santa Barbara, California
2009 Phillip and Ruth Hettleman Prize for Artistic and Scholarly Achievement, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
2008 Elected Member, American Society for Clinical Investigation, Ann Arbor, Michigan
2007 Jefferson-Pilot Fellowship in Academic Medicine
2007 Clinical Scientist in Translational Research Award, Burroughs-Wellcome Fund, Research Triangle Park, North Carolina
2005 New Scholar Award in Aging Research, Ellison Medical Foundation, Bethesda, Maryland
2003 Scholar Award for Cancer Research, William Guy Forbeck Research Foundation, Carbondale, Colorado
2003 Kimmel Scholar Award, The Sidney Kimmel Foundation for Cancer Research, Philadelphia, Pennsylvania
2003 Paul Beeson Physician Faculty Scholar in Aging Research