Norman "Ned" Sharpless (born September 20, 1966) is the current Director of the National Cancer Institute as a presidential appointee under President Donald Trump. In March 2019, health and human services secretary Alex Azar announced that Sharpless would serve as acting FDA commissioner. Sharpless was the former Professor of Medicine and 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, listed $GTHX under the NASDAQ, which is 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 affect the rate of molecular aging. He is also a founder of Sapere Bio (formerly HealthSpan Diagnostics), a clinical-phase biotechnology company measuring physiologic reserve to improve healthcare.
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 major histocompatibility complex and the p16INK4a/ARF loci as the most frequently reported disease associated loci in humans.
Sharpless was named to head the National Cancer Institute on June 10, 2017, and took office on October 17, 2017. After the abrupt announcement of Scott Gottlieb's departure as commissioner of the Food and Drug Administration on March 5, 2019, HHS secretary Azar announced that Sharpless would serve as acting commissioner.
Sharpless studied mathematics at the University of North Carolina at Chapel Hill, where he was a John Motley Morehead Scholar. He earned his medical degree with honors and distinction at the University of North Carolina School of Medicine. He completed his internship and residency at Massachusetts General Hospital in Boston, and a clinical and research fellowship at Dana-Farber Cancer Institute in Boston.
At the University of North Carolina at Chapel Hill, Sharpless ran a basic science laboratory that utilized genetically engineered mice to study cancer and aging, and was co-founder and co-director of the UNC Lineberger Mouse Phase I Unit. His research focused on how normal cells age and undergo malignant conversion.
In 2009, Sharpless’s lab identified p16INK4a expression in human peripheral blood T-lymphocytes as an easily measurable biomarker of human molecular age and developed a clinically applicable assay for potential personalized patient risk assessment, which was featured on BBC News and other international news agencies for its promise to eventually “measure” human aging. The biomarker was subsequently shown to be a clinical outcome predictor in kidney transplant. The biomarker assay was commercialized by a clinical-phase biotech company called Sapere Bio (formerly HealthSpan Dx), founded by Sharpless and his team.
In 2009, Sharpless and his team were the first to discover altered human INK4/ARF expression as the mechanism for the 9p21.3 genetic risk allele of atherosclerosis. This was first published study identifying the underlying mechanism of 9p21.3, a genetic risk variant with the strongest, and most consistent association with atherosclerosis in multiple, independent, large-scale GWASs (Genome Wide Association Studies). The findings remain to be the most plausible mechanism of 9p21.3 atherosclerosis risk up to this date.
In 2011, Sharpless and his team, using conditional p16INK4a knock-out mouse models, discovered that p16INK4a plays lineage-specific roles of tumor suppression or aging promotion in immune system, providing the first genetic evidence for lineage-specific pleiotropy in immune aging and genetic basis for heterogeneity of human aging and cancer susceptibility.
In 2013 Sharpless and his lab cataloged a large list of circular RNAs in human cell lines and mouse tissues using a whole genome sequencing strategy employing RNase R digestion. These were identified as highly stable transcripts, and reported the first link between circular RNAs and ALU Elements. Sharpless coined the term "backsplicing" to refer to the process by which these circular RNAs might be formed.
In August 2013, he was appointed director of UNC Lineberger Comprehensive Cancer Center.
Publications, awards, professional positions and honors
Sharpless has authored or co-authored more than 170 original reports, reviews and book chapters recorded in the PubMed.gov database and has served as an editor of Aging Cell and the Journal of Clinical Investigation. He has 12 issued or pending patents for his inventions. Sharpless’ honors include being the 2007 recipient of the Jefferson Pilot Award, the 2009 recipient of the Hettleman Prize for Scholarly Achievement, a 2010 recipient of a Glenn Award for Research in Biological Mechanisms of Aging, and a 2012 “Triangle Business Journal Health Care Hero.” He is an elected member of the American Society of Clinical Investigation (ASCI), the nation’s oldest honor society for physician-scientists, and the Association of American Physicians.
In 2016, Sharpless was elected to a three-year term on the Association of American Cancer Institutes’ board of directors. He is an appointed member of the National Institute of Aging’s National Advisory Council on Aging.
He has served on advisory boards of ASCI, the American Association of Cancer Research, the American Association of Cancer Institutes, the Glenn Foundation, the Ellison Medical Foundation and the Damon Runyon Cancer Research Foundation.
Sharpless is married to Dr. Julie L. Sharpless, an Associate Professor of Medicine at UNC in Neurosurgery and Endocrinology & Metabolism. They have two children, William Sharpless and Leigh Sharpless, where they currently live in Washington, D.C.
- "Gene Found to Switch Off Stem Cells During Aging". The New York Times. September 6, 2006. Retrieved September 30, 2015.
- Kim, WY; Sharpless, NE (October 20, 2006). "The regulation of INK4/ARF in cancer and aging". Cell. 127 (2): 265–75. doi:10.1016/j.cell.2006.10.003. PMID 17055429.
- Burd, Christin E.; Sorrentino, Jessica A.; Clark, Kelly S.; Darr, David B.; Krishnamurthy, Janakiraman; Deal, Allison M.; Bardeesy, Nabeel; Castrillon, Diego H.; Beach, David H. (January 17, 2013). "Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model". Cell. 152 (1–2): 340–351. doi:10.1016/j.cell.2012.12.010. ISSN 1097-4172. PMC 3718011. PMID 23332765.
- Sorrentino, J; Krishnamurthy, K; Tilley, S; Alb, JG; Burd, C; Sharpless, N (2014). "p16INK4a reporter mice reveal age-promoting effects of environmental toxicants". Journal of Clinical Investigation. 124 (1): 169–73. doi:10.1172/JCI70960. PMC 3871242. PMID 24334456.
- Demaria, Marco; O'Leary, Monique N.; Chang, Jianhui; Shao, Lijian; Liu, Su; Alimirah, Fatouma; Koenig, Kristin; Le, Catherine; Mitin, Natalia (February 1, 2017). "Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse". Cancer Discovery. 7 (2): 165–176. doi:10.1158/2159-8290.CD-16-0241. ISSN 2159-8274. PMC 5296251. PMID 27979832.
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- Liu, Y.; Sanoff, H. K.; Cho, H.; Burd, C. E.; Torrice, C.; Ibrahim, J. G.; Sharpless, N. E. (2009). "Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging". Aging Cell. 8 (4): 439–448. doi:10.1111/j.1474-9726.2009.00489.x. PMC 2752333. PMID 19485966.
- Tsygankov, D.; Liu, Y.; Sanoff, H. K.; Sharpless, N. E.; Elston, T. C. (2009). "A quantitative model for age-dependent expression of the p16INK4a tumor suppressor". Proceedings of the National Academy of Sciences. 106 (39): 16562–16567. doi:10.1073/pnas.0904405106. PMC 2757807. PMID 19805338.
- Gingell-Littlejohn, M; McGuinness, D; McGlynn, LM; Kingsmore, D; Stevenson, KS; Koppelstaetter, C; et al. (2013). "Pre-Transplant CDKN2A Expression in Kidney Biopsies Predicts Renal Function and Is a Future Component of Donor Scoring Criteria". PLoS ONE. 8 (7): e68133. doi:10.1371/journal.pone.0068133. PMC 3701657. PMID 23861858.
- Koppelstaetter, C.; Schratzberger, G.; Perco, P.; et al. (2008). "Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation". Aging Cell. 7 (4): 491–497. doi:10.1111/j.1474-9726.2008.00398.x. PMID 18462273.
- Braun, H; Schmidt, BMW; Raiss, M; et al. (2012). "Cellular Senescence Limits Regenerative Capacity and Allograft Survival". Journal of the American Society of Nephrology : JASN. 23 (9): 1467–1473. doi:10.1681/ASN.2011100967. PMC 3431409. PMID 22797186.
- Liu, Y; Sanoff, HK; Cho, H; Burd, CE; Torrice, C; Mohlke, KL; et al. (2009). "INK4/ARF Transcript Expression Is Associated with Chromosome 9p21 Variants Linked to Atherosclerosis". PLoS ONE. 4 (4): e5027. doi:10.1371/journal.pone.0005027. PMC 2660422. PMID 19343170.
- Lusis AJ. Genetics of Atherosclerosis" Trends in Genetics 2012;28(6):267-275. doi:10.1016/j.tig.2012.03.001
- Liu, Y.; Johnson, S. M.; Fedoriw, Y.; Rogers, A. B.; Yuan, H.; Krishnamurthy, J.; Sharpless, N. E. (2011). "Expression of p16INK4a prevents cancer and promotes aging in lymphocytes". Blood. 117 (12): 3257–3267. doi:10.1182/blood-2010-09-304402. PMC 3069667. PMID 21245485.
- Eshraghi, P.; Rudolph, K. L. (2011). "Lineage-specific pleiotropy in immune aging". Blood. 117 (12): 3250–3251. doi:10.1182/blood-2011-02-332650. PMID 21436077.
- Liu, Yan; Sharpless, Norman E (2009). "Tumor suppressor mechanisms in immune aging". Current Opinion in Immunology. 21 (4): 431–439. doi:10.1016/j.coi.2009.05.011. PMC 2725203. PMID 19535234.
- Burd, CE; Jeck, WR; Liu, Y; et al. (December 2, 2010). "Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk". PLOS Genetics. 6 (12): e1001233. doi:10.1371/journal.pgen.1001233. PMC 2996334. PMID 21151960.
- Jeck, WR; Sorrentino, JA; Wang, K; Slevin, MK; Burd, CE; Liu, J; Marzluff, WF; Sharpless, NE (February 2013). "Circular RNAs are abundant, conserved, and associated with ALU repeats". RNA. 19 (2): 141–57. doi:10.1261/rna.035667.112. PMC 3543092. PMID 23249747.
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