Jan Breslow

Last updated
Jan Breslow
Alma mater
Awards Heinrich 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.

Contents

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 PBB Protein APOE.jpg
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 Protein PCSK9 PDB 2p4e.png
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

Related Research Articles

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<span class="mw-page-title-main">Lipoprotein</span> Biochemical assembly whose purpose is to transport hydrophobic lipid molecules

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<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

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<span class="mw-page-title-main">Joseph L. Goldstein</span> American biochemist

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<span class="mw-page-title-main">Apolipoprotein</span> Proteins that bind lipids to transport them in body fluids

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<span class="mw-page-title-main">LDL receptor</span> Mammalian protein found in Homo sapiens

The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e. intermediate-density lipoprotein (IDL), and LDL particles. The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and IDL. In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. It belongs to the low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue.

<span class="mw-page-title-main">Apolipoprotein E</span> Cholesterol-transporting protein most notably implicated in Alzheimers disease

Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene APOE.

<span class="mw-page-title-main">Apolipoprotein B</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

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<span class="mw-page-title-main">Apolipoprotein C-III</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ABCA1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">APOA5</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein A-V is a protein that in humans is encoded by the APOA5 gene on chromosome 11. It is significantly expressed in liver. The protein encoded by this gene is an apolipoprotein and an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of several lipoprotein fractions including VLDL, HDL, chylomicrons. It is believed that apoA-V affects lipoprotein metabolism by interacting with LDL-R gene family receptors. Considering its association with lipoprotein levels, APOA5 is implicated in metabolic syndrome. The APOA5 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Apolipoprotein A-II</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein A-II is a protein that in humans is encoded by the APOA2 gene. It is the second most abundant protein of the high density lipoprotein particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. ApoA-II regulates many steps in HDL metabolism, and its role in coronary heart disease is unclear. Remarkably, defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia.

<span class="mw-page-title-main">PCSK9</span> Mammalian protein found in humans

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<span class="mw-page-title-main">Apabetalone</span> Chemical compound

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Nobuyo N. Maeda is a Japanese geneticist and medical researcher, who works on complex human diseases including atherosclerosis, diabetes and high blood pressure, and is particularly known for creating the first mouse model for atherosclerosis. Maeda has worked in the United States since 1978; as of 2017, she is the Robert H. Wagner Distinguished Professor at the University of North Carolina at Chapel Hill.

References

  1. 1 2 3 4 5 6 Creating the "Heart-Attack Mouse": A Model for Atherosclerosis, Rockefeller University , retrieved 16 January 2017
  2. 1 2 Jan Leslie Breslow, MD, American Society for Clinical Investigation , retrieved 17 January 2017
  3. 1 2 3 4 Jan L. Breslow, M.D., Rockefeller University , retrieved 16 January 2017
  4. 1 2 3 4 5 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. 1 2 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, archived from the original on 18 January 2017, retrieved 17 January 2017
  18. ↑ Marilyn G. Breslow, The New York Stem Cell Foundation, archived from the original on 22 December 2015, 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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