Norman Sharpless

Norman Sharpless
Sharpless in 2019
15th Director of the National Cancer Institute
In office
October 17, 2017 (2017-10-17) – April 30, 2022 (2022-04-30)
PresidentDonald Trump
Joe Biden
Preceded byHarold E. Varmus
Douglas R. Lowy (acting)
Succeeded byMonica Bertagnolli
Acting Commissioner of Food and Drugs
In office
April 5, 2019 (2019-04-05) – November 1, 2019 (2019-11-01)
PresidentDonald Trump
SecretaryAlex Azar
Preceded byScott Gottlieb
Succeeded byBrett Giroir (acting)
Personal details
Born (1966-09-20) September 20, 1966 (age 58)
Greensboro, North Carolina
NationalityAmerican
Alma mater
Known forp16LUC model
Scientific career
FieldsMolecular genetics
Institutions

Norman Edward "Ned" Sharpless (born September 20, 1966) is the previous Director of the National Cancer Institute (NCI). Before that, Sharpless was 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.[1]

Sharpless was named to head the NCI on June 10, 2017,[2] and took office on October 17, 2017. Sharpless also served as Acting Commissioner of the Food and Drugs from April 5, 2019[3][4] until November 1, 2019, after which he returned to the NCI.[5] He stepped down from the post at the end of April 2022.[6][7]

Education

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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.[8]

Career

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Sharpless, as acting Commissioner of Food and Drugs, in the Oval Office with President Donald Trump in 2019

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.[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] The biomarker assay was commercialized by a clinical-phase biotech company called Sapere Bio (formerly HealthSpan Dx), founded by Sharpless and his team.[15]

He has published numerous papers that show the role of p16INK4a in shutting down the stem cells that renew the body's various tissues.[16][17] He is also one of the founders of G1 Therapeutics, listed $GTHX under the NASDAQ, which is a clinical-stage biopharmaceutical company developing small-molecule therapies for the treatment of patients with 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.[18] 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.[19] 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.[20] 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[citation needed].

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.[21] 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).[22] The findings remain to be the most plausible mechanism of 9p21.3 atherosclerosis risk up to this date.[22]

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.[23][24][25]

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.[26]

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.[27]

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

Publications, awards, professional positions and honors

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Sharpless has authored or co-authored more than 170 original reports, reviews and book chapters recorded in the PubMed.gov database[28] 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.[29] Sharpless’ honors include being the 2007 recipient of the Jefferson Pilot Award Archived March 28, 2017, at the Wayback Machine, the 2009 recipient of the Hettleman Prize for Scholarly Achievement,[30] a 2010 recipient of a Glenn Award for Research in Biological Mechanisms of Aging,[31] and a 2012 “Triangle Business Journal Health Care Hero.”[32] He is an elected member of the American Society of Clinical Investigation (ASCI),[33] 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.[34] He is an appointed member of the National Institute of Aging’s National Advisory Council on Aging.[35]

Personal life

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Sharpless is married with two children. Sharpless' wife, Julie Sharpless, worked as a physician and associate professor at the University of North Carolina. Sharpless currently lives in Washington, D.C.

References

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  1. ^ a b "Norman E. Sharpless — UNC Lineberger Comprehensive Cancer Center". unclineberger.org. Archived from the original on April 14, 2015.
  2. ^ McGinley, Laurie (June 10, 2017). "UNC oncologist and researcher named head of the National Cancer Institute". Washington Post. Retrieved June 10, 2017.
  3. ^ Kaplan, Sheila; Hoffman, Jan (March 5, 2019). "F.D.A. Commissioner Scott Gottlieb, Who Fought Teenage Vaping, Resigns". The New York Times. ISSN 0362-4331. Retrieved May 12, 2022.
  4. ^ Kaplan, Sheila (March 12, 2019). "National Cancer Chief, Ned Sharpless, Named F.D.A.'s Acting Commissioner". The New York Times. ISSN 0362-4331. Retrieved May 12, 2022.
  5. ^ McGinley, Laurie (November 1, 2019). "Trump announces plan to nominate Texas cancer doctor to run FDA". The Washington Post. Retrieved November 2, 2019.
  6. ^ "Norman Sharpless steps down as director of the National Cancer Institute". National Institutes of Health (NIH) (Press release). NCI Press Office. April 4, 2022. Retrieved May 12, 2022.
  7. ^ Kaiser, Jocelyn (April 4, 2022). "Top U.S. cancer institute in line for new leadership as director announces departure". Science. doi:10.1126/science.abq3771. Retrieved May 12, 2022.
  8. ^ a b "Dr. Norman Sharpless appointed director of UNC Lineberger Comprehensive Cancer Center". UNC Health Care. Archived from the original on March 28, 2017. 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. doi:10.1111/j.1474-9726.2009.00489.x. PMC 2752333. PMID 19485966.
  10. ^ 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. Bibcode:2009PNAS..10616562T. doi:10.1073/pnas.0904405106. PMC 2757807. PMID 19805338.
  11. ^ "Hope for test to measure ageing". June 16, 2009.
  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. Bibcode:2013PLoSO...868133G. doi:10.1371/journal.pone.0068133. PMC 3701657. PMID 23861858.
  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 (4): 491–497. doi:10.1111/j.1474-9726.2008.00398.x. PMID 18462273. S2CID 37151355.
  14. ^ Braun, H; Schmidt, BMW; Raiss, M; et al. (2012). "Cellular Senescence Limits Regenerative Capacity and Allograft Survival". Journal of the American Society of Nephrology. 23 (9): 1467–1473. doi:10.1681/ASN.2011100967. PMC 3431409. PMID 22797186.
  15. ^ "Mon Artisan Direct - Isolation - VMC - Pompe à chaleur - Douche PMR". My Blog (in French). Archived from the original on May 16, 2022. Retrieved May 12, 2022.
  16. ^ "Gene Found to Switch Off Stem Cells During Aging". The New York Times. September 6, 2006. Retrieved September 30, 2015.
  17. ^ 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. S2CID 18280031.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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. Bibcode:2009PLoSO...4.5027L. doi:10.1371/journal.pone.0005027. PMC 2660422. PMID 19343170.
  22. ^ a b Lusis, AJ (2012). "Genetics of Atherosclerosis". Trends in Genetics. 28 (6): 267–275. doi:10.1016/j.tig.2012.03.001. PMC 3362664. PMID 22480919.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ 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.
  28. ^ "Sharpless NE[Author] - Search Results - PubMed". PubMed. Retrieved May 12, 2022.
  29. ^ "Norman E. Sharpless Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved March 28, 2017.
  30. ^ Outlaw, Jonathan (August 26, 2009). "Hettleman Prize winners span the arts and sciences". UNC News Archives. Retrieved May 12, 2022.
  31. ^ "Glenn Foundation for Medical Research Glenn Award for Research in Biological Mechanisms of Aging". glennfoundation.org. Retrieved May 12, 2022.
  32. ^ "Winner: Dr. Norman Sharpless – Innovator/Researcher". www.bizjournals.com. Retrieved March 28, 2017.
  33. ^ "The American Society for Clinical Investigation". www.the-asci.org. Retrieved March 28, 2017.
  34. ^ "AACI". www.aaci-cancer.org. Retrieved March 28, 2017.
  35. ^ Aging, National Institute on (September 7, 2011). "NACA Membership Roster". National Institute on Aging. Retrieved March 28, 2017.
[edit]
Government offices
Preceded by 15th Director of the National Cancer Institute
2017 – present 		Incumbent
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