Jan Breslow

Breslow attended Columbia College, Columbia University, gaining AB (1963) and MA (1964) degrees in chemistry. He then studied at Harvard Medical School, receiving his MD in 1968. He worked in pediatric medicine at the Boston Children's Hospital (1968–70) and then held a post-doctoral position at the National Heart, Lung, and Blood Institute (1970–73).{{citation |url=http://centennial.rucares.org/index.php?page=Heart-Attack_Mouse |title=Creating the "Heart-Attack Mouse": A Model for Atherosclerosis |publisher=Rockefeller University |access-date=16 January 2017 }}{{citation |url=http://www.rockefeller.edu/research/faculty/labheads/JanBreslow/ |title=Jan L. Breslow, M.D. |publisher=Rockefeller University |access-date=16 January 2017 }}

File:PBB Protein APOE.jpg]]

In 1973, he took up a post as head of the metabolism division of Boston Children's Hospital, as well as successively instructor, assistant and associate professor in pediatric medicine at Harvard Medical School. In 1984, he moved to Rockefeller University as a professor, and in 1986, was appointed Frederick Henry Leonhardt Professor at the Laboratory of Biochemical Genetics and Metabolism. In 2014, he was appointed director of the university's Sackler Center for Biomedicine and Nutrition. He also works at Rockefeller University Hospital as a senior physician and was physician-in-chief in the 1990s.

Breslow's research has focused on the genetic factors that govern an individual's predisposition to develop atherosclerosis. He started to work on the genetics of cholesterol handling in the late 1970s,{{citation |url=https://books.google.com/books?id=KIsRBAAAQBAJ&pg=PT138 |author=Jerry E. Bishop |author2=Michael Waldholz |title=Genome: The Story of the Most Astonishing Scientific Adventure of Our Time—the Attempt to Map All the Genes in the Human Body |year=2014 |publisher=Open Road Media |isbn=978-1-4976-0753-8 }} and in the early 1980s, with Vassilis Zannis, he was one of the earliest to dissect the different variants of human apolipoprotein E (ApoE), a component of very low-density lipoprotein.{{citation |pmc=2674716 |title=Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS |author=Robert W. Mahley |author2=Karl H. Weisgraber |author3=Yadong Huang |journal=Journal of Lipid Research |year=2009 |volume=50 |issue=Suppl |pages=S183–88 |pmid=19106071 |doi=10.1194/jlr.R800069-JLR200 |doi-access=free }} People with different ApoE variants are now known to have different risks not only of heart disease but also of Alzheimer's disease. In 1992, his group found that deleting the mouse gene for ApoE caused the animals to develop elevated blood cholesterol levels and atherosclerosis within around 6 months, on a normal diet.{{citation |author=Andrew S. Plump |author2=Jonathan D. Smith |author3=Tony Hayek |author4=Katriina Aalto-Setälä |author5=Annemarie Walsh |author6=Judy G. Verstuyft |author7=Edward M. Rubin |author8=Jan L. Breslow |title=Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells |journal=Cell |year=1992 |volume=71 |issue=2 |pages=343–53 |pmid=1423598 |doi=10.1016/0092-8674(92)90362-g|s2cid=29828640 }} Nobuyo Maeda's group at the University of North Carolina at Chapel Hill also independently created ApoE knockouts (apoe^−/−) that developed atherosclerosis at the same time.{{citation |url=https://www.researchgate.net/publication/21743258 |title=Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E |author=Sunny H. Zhang |author2=Robert L. Reddick |author3=Jorge A. Piedrahita |author4=Nobuyo Maeda |journal=Science |year=1992 |volume=258 |issue=5081 |pages=468–71 |doi=10.1126/science.1411543|pmid=1411543 |bibcode=1992Sci...258..468Z }}{{citation |url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/advanced.html |title=The Nobel Prize in Physiology or Medicine 2007: Advanced Information |publisher=The Nobel Foundation |access-date=16 January 2017 }}{{citation |title=Mouse models of atherosclerosis |author=Jan L. Breslow |journal=Science |year=1996 |volume=272 |issue=5262 |pages=685–88 |doi=10.1126/science.272.5262.685|pmid=8614828 |bibcode=1996Sci...272..685B |s2cid=33508623 }} The ApoE knockout was the earliest mouse model of the disease, and has been widely used in atherosclerosis research.{{citation |pmc=4023305 |title=Animal models of atherosclerosis |author=Fatemeh Ramezani Kapourchali |author2=Gangadaran Surendiran |author3=Li Chen |author4=Elisabeth Uitz |author5=Babak Bahadori |author6=Mohammed H. Moghadasian |journal=World Journal of Clinical Cases |year=2014 |volume=2 |issue=5 |pages= 126–32 |doi=10.12998/wjcc.v2.i5.126 |pmid=24868511 |doi-access=free }}{{citation |pmc=1853358 |title=A practical approach to using mice in atherosclerosis research |author=Stewart C. Whitman |journal=The Clinical Biochemist Reviews |year=2004 |volume=25 |issue=1 |pages=81–93 |pmid=18516202 }}

File:Protein PCSK9 PDB 2p4e.png]]

His group has subsequently researched other genes associated with atherosclerosis, and for example, in 2003, were among the first to identify and characterize PCSK9, which encodes an enzyme acting in a novel cholesterol regulatory pathway.{{citation |title=Genetics: A gene of rare effect |author=Stephen S. Hall |journal=Nature |year=2013 |volume=496 |issue=7444 |pages=152–55 |doi=10.1038/496152a|pmid=23579660 |bibcode=2013Natur.496..152H |doi-access=free }} Antibodies targeting PCSK9 were approved by the US FDA as a novel class of cholesterol-lowering drugs in 2015.{{citation|title=FDA approves Praluent to treat certain patients with high cholesterol|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455883.htm |publisher=FDA |date=24 July 2015 |access-date=18 January 2017 }}

Breslow is an elected fellow of the American Society for Clinical Investigation (1984),{{citation |url=https://www.the-asci.org/controllers/asci/AsciProfileController.php?pid=157538 |title=Jan Leslie Breslow, MD |publisher=American Society for Clinical Investigation |access-date=17 January 2017 }} US National Academy of Sciences (1995), Deutsche Akademie der Naturforscher Leopoldina (1996){{cite web|url=http://www.leopoldina.org/en/members/list-of-members/member/574/|title=List of Members|website=www.leopoldina.org|access-date=19 October 2017}} and the Institute of Medicine (1997). He served as president of the American Heart Association – using the position to lobby vigorously for more government funding for research into heart disease{{citation |title=Lobbyists seek to reslice NIH's pie |author=Eliot Marshall |year=1997 |journal=Science |volume=276 |issue=5311 |pages=344–46 |jstor=2893285 |doi=10.1126/science.276.5311.344|pmid=9139352 |s2cid=26468264 }} – and has received several awards from the association, including their Lifetime Research Achievement Award in 2010. He has also served as vice president of the American Society for Clinical Investigation. He has won the E. Mead Johnson Award of the American Academy of Pediatrics (1984), the Heinrich Wieland Prize (1991) and the Bristol-Myers Squibb Award for Cardiovascular Research (2000).{{citation |url=http://circ.ahajournals.org/content/101/23/e9054.long |title=Jan L. Breslow, MD, Receives 10th Annual Bristol-Myers Squibb Award |author=Ruth SoRelle |journal=Circulation |volume=101 |issue=23 |pages=E9054-5 |doi=10.1161/01.CIR.101.23.e9054 |pmid=10851226 |year=2000 }} In March 2013, Rockefeller University organized a symposium entitled "Genetics of Lipid Disorders and Atherosclerosis" to mark his seventieth birthday.{{citation |url=http://www.rockefeller.edu/breslow/ |title=A Symposium in Honor of Jan Breslow's 70th Birthday |publisher=Rockefeller University |date=15 March 2013 |access-date=17 January 2017 |archive-date=18 January 2017 |archive-url=https://web.archive.org/web/20170118051000/http://www.rockefeller.edu/breslow/ |url-status=dead }}

Breslow is married to Marilyn G. Breslow, an investment manager and sculptor; the couple have two sons.{{citation |url=https://nyscf.org/about-us/boards-councils/board-of-directors/item/229-marilyn-g-breslow |title=Marilyn G. Breslow |publisher=The New York Stem Cell Foundation |access-date=17 January 2017 |archive-date=22 December 2015 |archive-url=https://web.archive.org/web/20151222075902/http://nyscf.org/about-us/boards-councils/board-of-directors/item/229-marilyn-g-breslow |url-status=dead }}{{citation |url=http://marilynbreslow.com/marilyn-breslow-artist-statement/ |title=Marilyn Breslow: Artist Statement |work=Marilyn Breslow: Sculptor |access-date=17 January 2017 }} Breslow is one of the signatories of a letter entitled "No Need to Panic About Global Warming", which was published in The Wall Street Journal in 2012.[https://www.wsj.com/articles/no-need-to-panic-about-global-warming-1386195856 No Need to Panic About Global Warming], The Wall Street Journal, 27 January 2012, retrieved 27 February 2020

• {{citation |title=Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype |author=Kara N. Maxwell |author2=Jan L. Breslow |journal=Proceedings of the National Academy of Sciences USA |year=2004 |volume=101 |issue=18 |pages=7100–5 |doi=10.1073/pnas.0402133101 |pmid=15118091 |pmc=406472 |bibcode=2004PNAS..101.7100M |doi-access=free }}
• {{citation |author=Yutaka Nakashima |author2=Andrew S. Plump |author3=Elaine W. Raines |author4=Jan L. Breslow |author5=Russell Ross |title=ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |year=1994 |volume=14 |issue=1 |pages=133–40 |doi=10.1161/01.ATV.14.1.133 |pmid=8274468 |doi-access=free }}
• {{citation |author=Andrew S. Plump |author2=Jonathan D. Smith |author3=Tony Hayek |author4=Katriina Aalto-Setälä |author5=Annemarie Walsh |author6=Judy G. Verstuyft |author7=Edward M. Rubin |author8=Jan L. Breslow |title=Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells |journal=Cell |year=1992 |volume=71 |issue=2 |pages=343–53 |pmid=1423598 |doi=10.1016/0092-8674(92)90362-g|s2cid=29828640 }}
• {{citation |author=Katherine A. Hajjar |author2=Dov Gavishi |author3=Jan L. Breslow |author4=Ralph L. Nachman |title=Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis |journal=Nature |year=1989 |volume=339 |issue=6222 |pages=303–5 |doi=10.1038/339303a0 |pmid=2524666 |bibcode=1989Natur.339..303H |s2cid=4313247 }}
• {{citation |author=Vassilis I. Zannis |author2=Jan L. Breslow |title=Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification |journal=Biochemistry |year=1981 |volume=20 |issue=4 |pages=1033–41 |doi=10.1021/bi00507a059 |pmid=6260135 }}

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Category:1943 births

Category:Living people

Category:American pediatricians

Category:American medical researchers

Category:Columbia College (New York) alumni

Category:Harvard Medical School alumni

Category:Harvard Medical School faculty

Category:Rockefeller University faculty

Category:Members of the German National Academy of Sciences Leopoldina

Category:Members of the National Academy of Medicine