Norman Sharpless

Norman "Ned" Sharpless is Professor of Medicine & Genetics Chair, Director of University of North Carolina UNC Lineberger Comprehensive Cancer Center, Molecular Therapeutics, Wellcome Distinguished Professorship in Cancer Research. He has published numerous papers that show the role of p16INK4a in shutting down the stem cells that renew the body's various tissues. He is also one of the founders of G1 Therapeutics, a clinical-stage biopharmaceutical company developing novel, small-molecule therapies that address significant unmet needs in the treatment of cancer. Extending upon this work, Sharpless' team developed the p16LUC model, a genetically engineered mouse that 'glows' upon activation of the p16INK4a promoter due to insertion of firefly luciferase in place of the endogenous gene. Use of this system revealed the activation of p16INK4a in tissues surrounding nascent tumors, allowing scientists to non-invasively visualize the formation and progression of spontaneous cancers in living animals. Furthermore, this allele has made it feasible to better understand aging toxicology. Specifically, Ned's lab has used the p16LUC allele to understand how low dose toxic exposure over a lifetime can effect the rate of molecular aging.

Most recently, Sharpless with Judith Campisi, PhD, of the Buck Institute for Research on Aging, and colleagues demonstrated In 2016 how chemotherapy triggers cellular senescence, a pro-inflammatory stress response, which promotes the adverse effects of chemotherapy as well as cancer relapse and metastasis. Eliminating the senescent cells in mice prevented the side effects. He has also reported on meta-analyses of GWAS studies of aging and disease, identifying the and the p16INK4a/ARF loci as the most frequently reported disease associated loci in humans.

Sharpless runs a 15-person basic science laboratory that utilizes genetically engineered mice to study cancer and aging, and he is co-founder and co-director of the UNC Lineberger Mouse Phase I Unit.  His lab’s research has focused on how normal cells age and undergo malignant conversion and has received support from the National Institutes of Health (NCI, NIA and NIEHS), Sidney Kimmel Foundation for Cancer Research; the American Federation of Aging Research; the William Guy Forbeck Research Foundation; the Breast Cancer Research Foundation, the Ellison Medical Foundation and the Burroughs-Wellcome Foundation.

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