Norman Sharpless
{{Short description|American cancer researcher (born 1966)}}
{{Use mdy dates|date=August 2020}}
{{Infobox officeholder
| name = Norman Sharpless
| image = Ned Sharpless official portrait.jpg
| caption = Sharpless in 2019
| office = 15th Director of the National Cancer Institute
| president = Donald Trump
Joe Biden
| term_start = {{start date|2017|10|17}}
| term_end = {{end date|2022|4|30}}
| predecessor = Harold E. Varmus
Douglas R. Lowy (acting)
| successor = Monica Bertagnolli
| office1 = Acting Commissioner of Food and Drugs
| president1 = Donald Trump
| term_start1 = {{start date|2019|04|05}}
| term_end1 = {{end date|2019|11|01}}
| 1blankname1 = {{nowr|Secretary}}
| 1namedata1 = Alex Azar
| predecessor1 = Scott Gottlieb
| successor1 = Brett Giroir (acting)
| birth_date = {{birth date and age|1966|09|20}}
| birth_place = Greensboro, North Carolina
| nationality = American
|module =
{{Infobox scientist | embed=yes
| alma_mater = {{ublist|University of North Carolina at Chapel Hill|University of North Carolina School of Medicine}}
| workplaces = {{ublist|University of North Carolina at Chapel Hill|National Cancer Institute}}
|field = Molecular genetics
|known_for = p16LUC model
}}
}}
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.{{cite web |url=https://unclineberger.org/people/norman-e.-sharpless |title=Norman E. Sharpless — UNC Lineberger Comprehensive Cancer Center |website=unclineberger.org |url-status=dead |archive-url=https://web.archive.org/web/20150414014239/http://unclineberger.org/people/norman-e.-sharpless |archive-date=2015-04-14}}
Sharpless was named to head the NCI on June 10, 2017,{{cite news |title=UNC oncologist and researcher named head of the National Cancer Institute |url=https://www.washingtonpost.com/news/to-your-health/wp/2017/06/10/unc-oncologist-and-researcher-named-head-of-the-national-cancer-institute |newspaper=Washington Post |date=June 10, 2017 |access-date=June 10, 2017 |author=McGinley, Laurie}} and took office on October 17, 2017. Sharpless also served as Acting Commissioner of the Food and Drugs from April 5, 2019{{Cite news|last1=Kaplan|first1=Sheila|last2=Hoffman|first2=Jan|date=2019-03-05|title=F.D.A. Commissioner Scott Gottlieb, Who Fought Teenage Vaping, Resigns|language=en-US|work=The New York Times|url=https://www.nytimes.com/2019/03/05/health/scott-gottlieb-resigns-fda.html|access-date=2022-05-12|issn=0362-4331}}{{Cite news|last=Kaplan|first=Sheila|date=2019-03-12|title=National Cancer Chief, Ned Sharpless, Named F.D.A.'s Acting Commissioner|language=en-US|work=The New York Times|url=https://www.nytimes.com/2019/03/12/health/fda-ned-sharpless.html|access-date=2022-05-12|issn=0362-4331}} until November 1, 2019, after which he returned to the NCI.{{Cite news|url=https://www.washingtonpost.com/health/2019/11/01/top-hhs-official-run-fda-temporary-basis-while-trump-readies-nomination-texas-cancer-doctor/|title=Trump announces plan to nominate Texas cancer doctor to run FDA|last=McGinley|first=Laurie|date=2019-11-01|newspaper=The Washington Post|language=en|archive-url=|archive-date=|access-date=2019-11-02}} He stepped down from the post at the end of April 2022.{{cite press release |title=Norman Sharpless steps down as director of the National Cancer Institute |url=https://www.nih.gov/news-events/news-releases/norman-sharpless-steps-down-director-national-cancer-institute |access-date=12 May 2022 |work=National Institutes of Health (NIH) |publisher=NCI Press Office |date=4 April 2022 |language=EN}}{{cite news |last1=Kaiser |first1=Jocelyn |title=Top U.S. cancer institute in line for new leadership as director announces departure |url=https://www.science.org/content/article/top-u-s-cancer-institute-line-new-leadership-director-announces-departure |access-date=12 May 2022 |work=Science |date=April 4, 2022 |language=en |doi=10.1126/science.abq3771}}
Education
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.{{Cite web|url=http://news.unchealthcare.org/news/2013/august/dr-norman-sharpless-appointed-director-of-unc-lineberger-comprehensive-cancer-center|title=Dr. Norman Sharpless appointed director of UNC Lineberger Comprehensive Cancer Center|website=UNC Health Care|language=en|access-date=March 28, 2017|archive-date=March 28, 2017|archive-url=https://web.archive.org/web/20170328195333/http://news.unchealthcare.org/news/2013/august/dr-norman-sharpless-appointed-director-of-unc-lineberger-comprehensive-cancer-center|url-status=dead}}
Career
File:President Trump Announces Plan to Remove Flavored E-Cigarette Products From the Market (48721903623).jpg, 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.
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,{{cite journal |last1=Liu|first1=Y.|last2=Sanoff|first2=H. K.|last3=Cho|first3=H.|last4=Burd|first4=C. E.|last5=Torrice|first5=C. |last6=Ibrahim |first6=J.G.|last7=Sharpless|first7=N. E.|year=2009|title=Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging|journal=Aging Cell|volume=8|issue=4| pages=439–448|doi=10.1111/j.1474-9726.2009.00489.x| pmid=19485966|pmc=2752333}}{{cite journal|doi=10.1073/pnas.0904405106|pmid=19805338|volume=106|issue=39|title=A quantitative model for age-dependent expression of the p16INK4a tumor suppressor|year=2009|journal=Proceedings of the National Academy of Sciences|pages=16562–16567 |last1=Tsygankov|first1=D.|last2=Liu|first2=Y.|last3=Sanoff|first3=H. K.|last4=Sharpless|first4=N. E.|last5=Elston|first5=T. C. |pmc=2757807|bibcode=2009PNAS..10616562T|doi-access=free}} which was featured on BBC News and other international news agencies for its promise to eventually “measure” human aging.{{Cite news|url=http://news.bbc.co.uk/2/hi/health/8102811.stm|title=Hope for test to measure ageing|date=June 16, 2009}} The biomarker was subsequently shown to be a clinical outcome predictor in kidney transplant.{{cite journal|last1=Gingell-Littlejohn|first1=M|last2=McGuinness|first2=D|last3=McGlynn|first3=LM |last4=Kingsmore|first4=D|last5=Stevenson|first5=KS|last6=Koppelstaetter|first6=C |display-authors=etal |year=2013|title=Pre-Transplant CDKN2A Expression in Kidney Biopsies Predicts Renal Function and Is a Future Component of Donor Scoring Criteria |journal=PLOS ONE|volume=8|issue=7| page=e68133|doi=10.1371/journal.pone.0068133|pmid=23861858|pmc=3701657|bibcode=2013PLoSO...868133G|doi-access=free}}{{cite journal |last1=Koppelstaetter|first1=C.|last2=Schratzberger|first2=G.|last3=Perco|first3=P. |display-authors=etal |year=2008|title=Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation|journal=Aging Cell|volume=7|issue=4|pages=491–497 |doi=10.1111/j.1474-9726.2008.00398.x|pmid=18462273|s2cid=37151355|doi-access=free}}{{cite journal|last1=Braun|first1=H|last2=Schmidt|first2=BMW|last3=Raiss|first3=M |display-authors=etal |year=2012|title=Cellular Senescence Limits Regenerative Capacity and Allograft Survival|journal=Journal of the American Society of Nephrology|volume=23|issue=9 |pages=1467–1473|doi=10.1681/ASN.2011100967|pmid=22797186|pmc=3431409}} The biomarker assay was commercialized by a clinical-phase biotech company called Sapere Bio (formerly HealthSpan Dx), founded by Sharpless and his team.{{Cite web|title=Mon Artisan Direct - Isolation - VMC - Pompe à chaleur - Douche PMR|url=https://monartisandirect.fr/|access-date=2022-05-12|website=My Blog|language=fr-FR|archive-date=May 16, 2022|archive-url=https://web.archive.org/web/20220516043212/https://monartisandirect.fr/|url-status=dead}}
He has published numerous papers that show the role of p16INK4a in shutting down the stem cells that renew the body's various tissues.{{cite web|url=https://www.nytimes.com/2006/09/06/science/06cnd-stem.html|title=Gene Found to Switch Off Stem Cells During Aging|date=September 6, 2006|access-date=September 30, 2015|newspaper=The New York Times}}{{cite journal|last1=Kim|first1=WY|last2=Sharpless|first2=NE|date=October 20, 2006|title=The regulation of INK4/ARF in cancer and aging.|journal=Cell|volume=127|issue=2|pages=265–75|doi=10.1016/j.cell.2006.10.003|pmid=17055429|s2cid=18280031|doi-access=free}} 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.{{Cite journal|last1=Burd|first1=Christin E.|last2=Sorrentino|first2=Jessica A.|last3=Clark|first3=Kelly S.|last4=Darr|first4=David B.|last5=Krishnamurthy|first5=Janakiraman|last6=Deal|first6=Allison M.|last7=Bardeesy|first7=Nabeel|last8=Castrillon|first8=Diego H.|last9=Beach|first9=David H.|date=January 17, 2013|title=Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model|journal=Cell|volume=152|issue=1–2|pages=340–351|doi=10.1016/j.cell.2012.12.010|issn=1097-4172|pmc=3718011|pmid=23332765}} 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.{{cite journal|last1=Sorrentino|first1=J|last2=Krishnamurthy|first2=K|last3=Tilley|first3=S|last4=Alb|first4=JG|last5=Burd|first5=C|last6=Sharpless|first6=N|year=2014|title=p16INK4a reporter mice reveal age-promoting effects of environmental toxicants.|journal=Journal of Clinical Investigation|volume=124|issue=1|pages=169–73|doi=10.1172/JCI70960|pmc=3871242|pmid=24334456}} 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.{{Cite journal|last1=Demaria|first1=Marco|last2=O'Leary|first2=Monique N.|last3=Chang|first3=Jianhui|last4=Shao|first4=Lijian|last5=Liu|first5=Su|last6=Alimirah|first6=Fatouma|last7=Koenig|first7=Kristin|last8=Le|first8=Catherine|last9=Mitin|first9=Natalia|date=February 1, 2017|title=Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse|url= |journal=Cancer Discovery|language=en|volume=7|issue=2|pages=165–176|doi=10.1158/2159-8290.CD-16-0241|issn=2159-8274|pmc=5296251|pmid=27979832}} 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|date=July 2022}}.
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.{{cite journal|last1=Liu|first1=Y|last2=Sanoff|first2=HK|last3=Cho|first3=H|last4=Burd|first4=CE |last5=Torrice|first5=C|last6=Mohlke|first6=KL |display-authors=etal |year=2009|title=INK4/ARF Transcript Expression Is Associated with Chromosome 9p21 Variants Linked to Atherosclerosis|journal=PLOS ONE|volume=4|issue=4 |page=e5027|doi=10.1371/journal.pone.0005027 |pmid=19343170|pmc=2660422|bibcode=2009PLoSO...4.5027L|doi-access=free}} 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).{{cite journal | last1 = Lusis | first1 = AJ | year = 2012 | title = Genetics of Atherosclerosis | journal = Trends in Genetics | volume = 28 | issue = 6| pages = 267–275 | doi = 10.1016/j.tig.2012.03.001 | pmid = 22480919 | pmc = 3362664 }} 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.{{cite journal|doi=10.1182/blood-2010-09-304402|pmid=21245485|volume=117|issue=12|title=Expression of p16INK4a prevents cancer and promotes aging in lymphocytes |year=2011|journal=Blood|pages=3257–3267|last1=Liu|first1=Y.|last2=Johnson|first2=S. M.|last3=Fedoriw|first3=Y.|last4=Rogers|first4=A. B.|last5=Yuan|first5=H.|last6=Krishnamurthy|first6=J.|last7=Sharpless|first7=N. E.|pmc=3069667}}{{cite journal |doi=10.1182/blood-2011-02-332650|pmid=21436077|volume=117|issue=12|title=Lineage-specific pleiotropy in immune aging|year=2011 |journal=Blood|pages=3250–3251|last1=Eshraghi|first1=P.|last2=Rudolph|first2=K. L.|doi-access=free}}{{cite journal |doi=10.1016/j.coi.2009.05.011|pmid=19535234|volume=21|issue=4|title=Tumor suppressor mechanisms in immune aging|year=2009 |journal=Current Opinion in Immunology|pages=431–439|last1=Liu|first1=Yan|last2=Sharpless|first2=Norman E|pmc=2725203}}
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.{{cite journal|last1=Burd|first1=CE|last2=Jeck|first2=WR |last3=Liu|first3=Y|display-authors=etal|title=Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk.|journal=PLOS Genetics|date=December 2, 2010 |volume=6|issue=12|pages=e1001233 |pmid=21151960 |doi=10.1371/journal.pgen.1001233|pmc=2996334 |doi-access=free }}
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.{{cite journal |last1=Jeck |first1=WR |last2=Sorrentino |first2=JA |last3=Wang |first3=K |last4=Slevin |first4=MK |last5=Burd |first5=CE |last6=Liu |first6=J |last7=Marzluff |first7=WF |last8=Sharpless |first8=NE |title=Circular RNAs are abundant, conserved, and associated with ALU repeats. |journal=RNA |date=February 2013 |volume=19 |issue=2 |pages=141–57 |doi=10.1261/rna.035667.112 |pmid=23249747|pmc=3543092}}
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{{Cite web|title=Sharpless NE[Author] - Search Results - PubMed|url=https://pubmed.ncbi.nlm.nih.gov/?term=Sharpless%2520NE%255BAuthor%255D&cauthor=true&cauthor_uid=30673081|access-date=2022-05-12|website=PubMed|language=en}} and has served as an editor of [http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1474-9726 Aging Cell] and the [https://www.jci.org/ Journal of Clinical Investigation]. He has 12 issued or pending patents for his inventions.{{Cite web |url=http://patents.justia.com/inventor/norman-e-sharpless|title=Norman E. Sharpless Inventions, Patents and Patent Applications - Justia Patents Search|website=patents.justia.com|language=en|access-date=March 28, 2017}} Sharpless’ honors include being the 2007 recipient of the [http://www.med.unc.edu/www/about/about-the-school-of-medicine-1/awards/jefferson-pilot-fellowships-in-academic-medicine#section-8 Jefferson Pilot Award] {{Webarchive|url=https://web.archive.org/web/20170328200320/http://www.med.unc.edu/www/about/about-the-school-of-medicine-1/awards/jefferson-pilot-fellowships-in-academic-medicine#section-8 |date=March 28, 2017 }}, the 2009 recipient of the Hettleman Prize for Scholarly Achievement,{{Cite web|last=Outlaw|first=Jonathan|date=2009-08-26|title=Hettleman Prize winners span the arts and sciences|url=https://uncnewsarchive.unc.edu/2009/08/26/hettleman-prize-winners-span-the-arts-and-sciences-4/|access-date=2022-05-12|website=UNC News Archives|language=en-US}} a 2010 recipient of a Glenn Award for Research in Biological Mechanisms of Aging,{{Cite web|title=Glenn Foundation for Medical Research Glenn Award for Research in Biological Mechanisms of Aging|url=http://glennfoundation.org/awards-programs/glenn-awards/|access-date=2022-05-12|website=glennfoundation.org}} and a 2012 “Triangle Business Journal Health Care Hero.”{{Cite web|url=http://www.bizjournals.com/triangle/print-edition/2012/03/23/winner-dr-norman-sharpless--.html|title=Winner: Dr. Norman Sharpless – Innovator/Researcher| website=www.bizjournals.com| access-date=March 28, 2017}}
He is an elected member of the American Society of Clinical Investigation (ASCI),{{Cite web |url=https://www.the-asci.org/controllers/asci/AsciProfileController.php?pid=500652|title=The American Society for Clinical Investigation|website=www.the-asci.org|language=en-US|access-date=March 28, 2017}} 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.{{Cite web|url=http://www.aaci-cancer.org/board.asp|title=AACI|website=www.aaci-cancer.org|access-date=March 28, 2017}} He is an appointed member of the National Institute of Aging’s National Advisory Council on Aging.{{Cite news|url=https://www.nia.nih.gov/about/naca-membership-roster|title=NACA Membership Roster|last=Aging|first=National Institute on |date=September 7, 2011|work=National Institute on Aging|access-date=March 28, 2017}}
Personal life
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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External links
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Category:Food and Drug Administration people
Category:University of North Carolina at Chapel Hill alumni
Category:University of North Carolina School of Medicine alumni
Category:University of North Carolina at Chapel Hill faculty