Norman Sharpless

Norman Sharpless
Born Norman Edward Sharpless
(1966-09-20) September 20, 1966
Greensboro, North Carolina
Nationality American
Other names Ned Sharpless
Occupation Director, Lineberger Comprehensive Cancer Center Founder, G1 Therapeutics ($GTHX)
Notable work Wellcome Distinguished Professor, American Society of Clinical Investigation Member, Association of American Cancer Institute board of directors,

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.[1] He has published numerous papers that show the role of p16INK4a in shutting down the stem cells that renew the body's various tissues.[2][3] 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.[4] 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.[5]

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.[6] 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.[7]

Education

Sharpless studied mathematics at the University of North Carolina at Chapel Hill, where he was a John Motley Morehead Scholar. He earned earned his bachelor of science and then his medical degree with honors and distinction at UNC-Chapel Hill. 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.[8]

Career

Sharpless runs a 15-person basic science laboratory which 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 research has focused on how normal cells age and undergo malignant conversion.[1]

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,[9][10] which was featured on BBC News and other international news agencies for its promise to eventually “measure” human aging.[11] The biomarker was subsequently shown to be a clinical outcome predictor in kidney transplant.[12][13][14] Currently, the biomarker assay is being commercialized in an early-stage start-up company called HealthSpan Dx, founded by Sharpless and his team.[15]

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.[16] 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).[17] The findings remain to be the most plausible mechanism of 9p21.3 atherosclerosis risk up to this date.[17]

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.[18][19][20]

In 2010 Sharpless's lab reported the first known human circular RNA produced from a long non-coding RNA, and linked its expression to alleles strongly associated with risk of atherosclerosis.[21]

In August 2013, he was appointed director of UNC Lineberger Comprehensive Cancer Center.[8]

IBM Watson

Sharpless has been using IBM's Watson to determine the best treatment options for patients.[22] Watson was trained, as it was to compete on Jeopardy! for which it had to read and digest all of Wikipedia, but for this use all papers on oncology, which task was completed in a matter of weeks.[23] In addition, Watson was programmed to read and add to its database the roughly 8,000 new oncology papers being published every day.[23] To verify its usefulness, Sharpless gave Watson 1000 recent cases at UNC, at least 990 of which Watson identified the diagnoses and treatments picked by the UNC oncology team, but for over 300 of the cases found new diagnoses and treatments the team had missed and possibly could have clinical relevance. As a consequence, Watson is now part of the UNC oncology team, as it has become elsewhere.[23]

Awards and Honorable Positions

He has authored more than 130 original reports, reviews and book chapters[24] and is an editor of Aging Cell and the Journal of Clinical Investigation. He has 12 issued or pending patents for his inventions.[25]  Sharpless’ honors include being the 2007 recipient of the Jefferson Pilot Award, the 2009 recipient of the Hettleman Prize for Scholarly Achievement,[26] a 2010 recipient of a Glenn Award for Research in Biological Mechanisms of Aging, and a 2012 “Triangle Business Journal Health Care Hero.”[27]

Sharpless is an elected member of the American Society of Clinical Investigation (ASCI),[28] the nation’s oldest honor society for physician-scientists, and the Association of American Physicians.

In 2016, he was elected to a three-year term on the Association of American Cancer Institutes’ board of directors.[29] He is an appointed member of the National Institute of Aging’s National Advisory Council on Aging.[30]

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.

Personal life

Sharpless married Dr. Julie L. Sharpless, an Associate Professor of Medicine at UNC in Neurosurgery and Endocrinology & Metabolism. They have two children, William and Leigh, where they currently live in Chapel Hill, NC.

References

  1. 1 2 https://unclineberger.org/people/norman-e.-sharpless
  2. ↑ "Gene Found to Switch Off Stem Cells During Aging". The New York Times. September 6, 2006. Retrieved September 30, 2015.
  3. ↑ Kim, WY; Sharpless, NE (October 20, 2006). "The regulation of INK4/ARF in cancer and aging.". Cell. 127 (2): 265–75. PMID 17055429. doi:10.1016/j.cell.2006.10.003.
  4. ↑ 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. ISSN 1097-4172. PMC 3718011 Freely accessible. PMID 23332765. doi:10.1016/j.cell.2012.12.010.
  5. ↑ Sorrentino, J; Krishnamurthy, K; Tilley, S; Alb, JG; Burd, C; Sharpless, N. "p16INK4a reporter mice reveal age-promoting effects of environmental toxicants.". Journal of Clinical Investigation. PMID 24334456.
  6. ↑ 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. ISSN 2159-8274. PMC 5296251 Freely accessible. PMID 27979832. doi:10.1158/2159-8290.CD-16-0241.
  7. ↑ McGinley, Laurie (June 10, 2017). "UNC oncologist and researcher named head of the National Cancer Institute". Washington Post. Retrieved June 10, 2017.
  8. 1 2 "Dr. Norman Sharpless appointed director of UNC Lineberger Comprehensive Cancer Center". UNC Health Care. Retrieved March 28, 2017.
  9. ↑ 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. http://doi.org/10.1111/j.1474-9726.2009.00489.x
  10. ↑ Tsygankov D, Liu Y, Sanoff HK, Sharpless NE, Elston TC. A quantitative model for age-dependent expression of the p16INK4a tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(39):16562-16567. doi:10.1073/pnas.0904405106.
  11. ↑ http://news.bbc.co.uk/2/hi/health/8102811.stm
  12. ↑ 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
  13. ↑ 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: 491–497. doi:10.1111/j.1474-9726.2008.00398.x
  14. ↑ Braun H, Schmidt BMW, Raiss M, et al. Cellular Senescence Limits Regenerative Capacity and Allograft Survival. Journal of the American Society of Nephrology : JASN. 2012;23(9):1467-1473. doi:10.1681/ASN.2011100967.
  15. ↑ http://www.healthspandiagnostics.com/
  16. ↑ 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
  17. 1 2 Lusis AJ. Genetics of Atherosclerosis. Trends in Genetics. 2012;28(6):267-275. doi:10.1016/j.tig.2012.03.001.
  18. ↑ 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. Accessed April 1, 2017. https://doi.org/10.1182/blood-2010-09-304402.
  19. ↑ Eshraghi, P., & Rudolph, K. L. (2011). Lineage-specific pleiotropy in immune aging. Blood, 117(12), 3250-3251. Accessed April 1, 2017. https://doi.org/10.1182/blood-2011-02-332650.
  20. ↑ Liu Y, Sharpless NE. Tumor Suppressor Mechanisms in Immune Ageing. Current Opinion in Immunology. 2009;21(4):431-439. doi:10.1016/j.coi.2009.05.011.
  21. ↑ 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. PMC 2996334 Freely accessible. PMID 21151960. doi:10.1371/journal.pgen.1001233.
  22. ↑ "Q&A with Dr. Norman Sharpless, Enlisting Watson in the Fight Against Cancer « A Smarter Planet Blog A Smarter Planet Blog". Asmarterplanet.com. Retrieved September 30, 2015.
  23. 1 2 3 interview with Charlie Rose for "60 Minutes", on CBS, September 10, 2016.
  24. ↑ pubmeddev. "(Sharpless NE[Author]) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved March 28, 2017.
  25. ↑ "Norman E. Sharpless Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved March 28, 2017.
  26. ↑ http://uncnewsarchive.unc.edu/2009/08/26/hettleman-prize-winners-span-the-arts-and-sciences-4/
  27. ↑ "Winner: Dr. Norman Sharpless – Innovator/Researcher". www.bizjournals.com. Retrieved March 28, 2017.
  28. ↑ "The American Society for Clinical Investigation". www.the-asci.org. Retrieved March 28, 2017.
  29. ↑ "AACI". www.aaci-cancer.org. Retrieved March 28, 2017.
  30. ↑ Aging, National Institute on (September 7, 2011). "NACA Membership Roster". National Institute on Aging. Retrieved March 28, 2017.
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