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Aging Biology and Cancer Section

Norman E. “Ned” Sharpless, M.D.

Norman “Ned” Sharpless, MD, Chief

Norman E. “Ned” Sharpless, M.D., was officially sworn in as the 15th director of the National Cancer Institute (NCI) on October 17, 2017. Prior to his appointment, Dr. Sharpless served as the director of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, a position he held since January 2014.

Dr. Sharpless was a Morehead Scholar at UNC–Chapel Hill and received his undergraduate degree in mathematics. He went on to pursue his medical degree from the UNC School of Medicine, graduating with honors and distinction in 1993. He then completed his internal medicine residency at the Massachusetts General Hospital and a hematology/oncology fellowship at Dana-Farber/Partners Cancer Care, both of Harvard Medical School in Boston.

After 2 years on the faculty at Harvard Medical School, he joined the faculty of the UNC School of Medicine in the Departments of Medicine and Genetics in 2002. He became the Wellcome Professor of Cancer Research at UNC in 2012.

Dr. Sharpless is a member of the Association of American Physicians as well as the American Society for Clinical Investigation (ASCI), the nation’s oldest honor society for physician–scientists, and served on the ASCI council from 2011 to 2014. Dr. Sharpless was an associate editor of Aging Cell and deputy editor of the Journal of Clinical Investigation. He has authored more than 150 original scientific papers, reviews, and book chapters, and is an inventor on 10 patents. He cofounded two clinical-stage biotechnology companies: G1 Therapeutics and HealthSpan Diagnostics.

In addition to serving as Director of NCI, Dr. Sharpless continues his research in understanding the biology of the aging process that promotes the conversion of normal self-renewing cells into dysfunctional cancer cells. Dr. Sharpless has made seminal contributions to the understanding of the relationship between aging and cancer, and in the preclinical development of novel therapeutics for melanoma, lung cancer, and breast cancer.

The Aging Biology and Cancer Section, led by Ned Sharpless, studies the biology of the aging process that promotes the conversion of normal self-renewing cells into dysfunctional cancer cells using genetically engineered mice. The Section has described novel regulators of metastasis, including p16INK4a, a tumor suppressor and aging biomarker which functions by limiting cell-cycle progression and promoting cellular senescence. p16INK4a binds and inhibits cyclin-dependent kinase 4/6 (CDK4/6) activity, thereby promoting a retinoblastoma (RB)-dependent cell-cycle arrest. Pharmacological approaches to protecting hematopoietic stem cells in vivo from chemotherapy-induced exhaustion have been developed through transient CDK4/6 inhibition. The Section is also studying circular RNAs (ecircRNA), a novel form of non-coding RNA. Bioinformatic approaches identified that ecircRNAs are abundant, stable, conserved and non-random products of RNA splicing that could be involved in the control of gene expression.

Research Areas

  • Cell cycle control in cancer and aging
  • Pharmacological approaches to protecting stem cells in vivo
  • Characterization of circular RNAs, a novel form of non-coding RNA

Representative Publications

  1. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114:1299-1307, 2004.
  2. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 443(28):453-457, 2006.
  3. Burd CE, Sorrentino JA, Clark KS, Darr DB, Krishnamurthy J, Deal AM, Bardeesy N, Castrillon DH, Beach DH, Sharpless NE. Monitoring tumorigenesis and senescence in vivo with p16INK4a-luciferase model. Cell. 152:340-351, 2013.
  4. He S, Roberts PJ, Sorrentino JA, Bisi JE, Storrie-White H, Tiessen RG, Makhuli KM, Wargin WA, Tadema H, van Hoogdalem E-J, Strum JC, Malik R, Sharpless NE. Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion. Sci. Transl. Med. 9, eaal3986, 2017.
  5. He S, Sharpless NE. Senescence in health and disease. Cell. 169:1000-1011, 2017.