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Jan Breslow

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Jan Breslow
Alma mater
AwardsHeinrich Wieland Prize (1991)
Scientific career
Institutions

Jan Leslie Breslow (born 1943)[1][2] is an American physician and medical researcher who studies atherosclerosis. As of 2017, he is Frederick Henry Leonhardt Professor at Rockefeller University and directs the university's Laboratory of Biochemical Genetics and Metabolism.

Biography

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).[1][3]

Human apolipoprotein E

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.[1][3] In 2014, he was appointed director of the university's Sackler Center for Biomedicine and Nutrition.[3] He also works at Rockefeller University Hospital as a senior physician and was physician-in-chief in the 1990s.[1][3]

Research

Breslow's research has focused on the genetic factors that govern an individual's predisposition to develop atherosclerosis.[4] He started to work on the genetics of cholesterol handling in the late 1970s,[5] 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.[6] People with different ApoE variants are now known to have different risks not only of heart disease but also of Alzheimer's disease.[4] 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.[7] 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.[8][9][10] The ApoE knockout was the earliest mouse model of the disease, and has been widely used in atherosclerosis research.[10][11][12]

Human PCSK9

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.[13] Antibodies targeting PCSK9 were approved by the US FDA as a novel class of cholesterol-lowering drugs in 2015.[14]

Awards and honours

Breslow is an elected fellow of the American Society for Clinical Investigation (1984),[2] US National Academy of Sciences (1995), Deutsche Akademie der Naturforscher Leopoldina (1996)[15] and the Institute of Medicine (1997).[4] He served as president of the American Heart Association – using the position to lobby vigorously for more government funding for research into heart disease[16] – and has received several awards from the association, including their Lifetime Research Achievement Award in 2010.[1] He has also served as vice president of the American Society for Clinical Investigation.[4] 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).[1][4] In March 2013, Rockefeller University organized a symposium entitled "Genetics of Lipid Disorders and Atherosclerosis" to mark his seventieth birthday.[17]

Personal life

Breslow is married to Marilyn G. Breslow, an investment manager and sculptor; the couple have two sons.[18][19] 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.[20]

Selected publications

  • Kara N. Maxwell; Jan L. Breslow (2004), "Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype", Proceedings of the National Academy of Sciences USA, 101 (18): 7100–5, Bibcode:2004PNAS..101.7100M, doi:10.1073/pnas.0402133101, PMC 406472, PMID 15118091
  • Yutaka Nakashima; Andrew S. Plump; Elaine W. Raines; Jan L. Breslow; Russell Ross (1994), "ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree", Arteriosclerosis, Thrombosis, and Vascular Biology, 14 (1): 133–40, doi:10.1161/01.ATV.14.1.133, PMID 8274468
  • Andrew S. Plump; Jonathan D. Smith; Tony Hayek; Katriina Aalto-Setälä; Annemarie Walsh; Judy G. Verstuyft; Edward M. Rubin; Jan L. Breslow (1992), "Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells", Cell, 71 (2): 343–53, doi:10.1016/0092-8674(92)90362-g, PMID 1423598, S2CID 29828640
  • Katherine A. Hajjar; Dov Gavishi; Jan L. Breslow; Ralph L. Nachman (1989), "Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis", Nature, 339 (6222): 303–5, Bibcode:1989Natur.339..303H, doi:10.1038/339303a0, PMID 2524666, S2CID 4313247
  • Vassilis I. Zannis; Jan L. Breslow (1981), "Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification", Biochemistry, 20 (4): 1033–41, doi:10.1021/bi00507a059, PMID 6260135

References

  1. ^ a b c d e f Creating the "Heart-Attack Mouse": A Model for Atherosclerosis, Rockefeller University, retrieved 16 January 2017
  2. ^ a b Jan Leslie Breslow, MD, American Society for Clinical Investigation, retrieved 17 January 2017
  3. ^ a b c d Jan L. Breslow, M.D., Rockefeller University, retrieved 16 January 2017
  4. ^ a b c d e Ruth SoRelle (2000), "Jan L. Breslow, MD, Receives 10th Annual Bristol-Myers Squibb Award", Circulation, 101 (23): E9054-5, doi:10.1161/01.CIR.101.23.e9054, PMID 10851226
  5. ^ Jerry E. Bishop; Michael Waldholz (2014), Genome: The Story of the Most Astonishing Scientific Adventure of Our Time—the Attempt to Map All the Genes in the Human Body, Open Road Media, ISBN 978-1-4976-0753-8
  6. ^ Robert W. Mahley; Karl H. Weisgraber; Yadong Huang (2009), "Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS", Journal of Lipid Research, 50 (Suppl): S183–88, doi:10.1194/jlr.R800069-JLR200, PMC 2674716, PMID 19106071
  7. ^ Andrew S. Plump; Jonathan D. Smith; Tony Hayek; Katriina Aalto-Setälä; Annemarie Walsh; Judy G. Verstuyft; Edward M. Rubin; Jan L. Breslow (1992), "Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells", Cell, 71 (2): 343–53, doi:10.1016/0092-8674(92)90362-g, PMID 1423598, S2CID 29828640
  8. ^ Sunny H. Zhang; Robert L. Reddick; Jorge A. Piedrahita; Nobuyo Maeda (1992), "Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E", Science, 258 (5081): 468–71, Bibcode:1992Sci...258..468Z, doi:10.1126/science.1411543, PMID 1411543
  9. ^ The Nobel Prize in Physiology or Medicine 2007: Advanced Information, The Nobel Foundation, retrieved 16 January 2017
  10. ^ a b Jan L. Breslow (1996), "Mouse models of atherosclerosis", Science, 272 (5262): 685–88, Bibcode:1996Sci...272..685B, doi:10.1126/science.272.5262.685, PMID 8614828, S2CID 33508623
  11. ^ Fatemeh Ramezani Kapourchali; Gangadaran Surendiran; Li Chen; Elisabeth Uitz; Babak Bahadori; Mohammed H. Moghadasian (2014), "Animal models of atherosclerosis", World Journal of Clinical Cases, 2 (5): 126–32, doi:10.12998/wjcc.v2.i5.126, PMC 4023305, PMID 24868511
  12. ^ Stewart C. Whitman (2004), "A practical approach to using mice in atherosclerosis research", The Clinical Biochemist Reviews, 25 (1): 81–93, PMC 1853358, PMID 18516202
  13. ^ Stephen S. Hall (2013), "Genetics: A gene of rare effect", Nature, 496 (7444): 152–55, Bibcode:2013Natur.496..152H, doi:10.1038/496152a, PMID 23579660
  14. ^ FDA approves Praluent to treat certain patients with high cholesterol, FDA, 24 July 2015, retrieved 18 January 2017
  15. ^ "List of Members". www.leopoldina.org. Retrieved 19 October 2017.
  16. ^ Eliot Marshall (1997), "Lobbyists seek to reslice NIH's pie", Science, 276 (5311): 344–46, doi:10.1126/science.276.5311.344, JSTOR 2893285, PMID 9139352, S2CID 26468264
  17. ^ A Symposium in Honor of Jan Breslow's 70th Birthday, Rockefeller University, 15 March 2013, retrieved 17 January 2017
  18. ^ Marilyn G. Breslow, The New York Stem Cell Foundation, retrieved 17 January 2017
  19. ^ "Marilyn Breslow: Artist Statement", Marilyn Breslow: Sculptor, retrieved 17 January 2017
  20. ^ No Need to Panic About Global Warming, The Wall Street Journal, 27 January 2012, retrieved 27 February 2020
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