The Rader laboratory
is focused on two major themes: 1) novel pathways regulating lipid and lipoprotein metabolism and atherosclerosis inspired by unbiased studies of human genetics; 2) factors regulating the structure and function of high density lipoproteins and the process of reverse cholesterol transport and their relationship to atherosclerosis. A variety of basic cell and molecular laboratory techniques, mouse models, and translational research approaches are used in addressing these questions.
Some examples of ongoing projects are:
1) The roles of sortilin (gene SORT1) and tribbles-1 (gene TRIB1) in lipoprotein metabolism and atherosclerosis. Variants at the SORT1 locus are among the most strongly associated with LDL cholesterol and (coronary artery disease) in the human genome, and variants at the TRIB1 locus are significantly associated with all major plasma lipid traits and CAD. A variety of tissue-specific deleted mouse models, gene targeting in iPS cells with differentiation to hepatocytes, and cell biologic and biochemical approaches are being employed.
2) Functional genomics and mechanistic studies of a number of additional genes at loci significantly associated with lipid and metabolic traits, CAD, or other cardiovascular traits. Most of these genes harbor rare coding variants associated with these traits. In addition to elucidating fundamental mechanisms by which the protein influences relevant biology, the influence of specific mutations on protein structure and function are being explored.
3) Molecular regulation of HDLmetabolism and reverse cholesterol transport using cells, mice, and humans
4) Deep phenotyping of humans with low-frequency and rare variants in genes influencing lipid and cardiovascular traits, including the generation of iPS cells and differentiation to a variety of relevant cell types
11th floor, Smilow Center for Translational Research
9th floor Maloney Building, Hospital of The University of Pennsylvania
Wolf JH, Holmes MV, Fouraschen S, Keating BJ, Baker T, Emond J, Rader DJ, Shaked A, Olthoff KM: Serum lipid expression correlates with function and regeneration following living donor liver transplantation. Liver Transpl 22(1): 103-101, Jan 2016.
Kastelein JJ, Nissen SE, Rader DJ, Hovingh GK, Wang MD, Shen T, Krueger KA: Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study. Eur Heart J. Jan 2016 Notes: Epub ahead of print
Ibrahim S, Somanathan S, Billheimer J, Wilson JM, Rader DJ : Stable Liver-specific Expression of Human IDOL in Humanized Mice Raises Plasma Cholesterol. Cardiovasc Res. Jan 2016 Notes: Epub ahead of print.
Herzog E, Pragst I, Waelchli M, Gille A, Schenk S, Mueller-Cohrs J, Diditchenko S, Zanoni P, Cuchel M, Seubert A, Rader DJ, Wright SD: Reconstituted high-density lipoprotein can elevate plasma alanine aminotransferase by transient depletion of hepatic cholesterol: role of the phospholipid component. J Appl Toxicol. Dec 2015 Notes: Epub ahead of print.
Voight BF, Rader DJ: Human genetics shines a light on ischaemic stroke. Lancet Neurol. Dec 2015 Notes: Epub ahead of print.
Khera AV, Millar JS, Ruotolo G, Wang MD, Rader DJ : Potent peroxisome proliferator-activated receptor-α agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome. Eur Heart J 36(42): 3020-3022, Nov 2015.
Hegele RA, Gidding SS, Ginsberg HN, McPherson R, Raal FJ, Rader DJ, Robinson JG, Welty FK : Nonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement From ATVB Council. Arterioscler Thromb Vasc Biol 35(11): 2269-2268, Nov 2015.
Natarajan P, Kohli P, Baber U, Nguyen KD, Sartori S, Reilly DF, Mehran R, Muntendam P, Fuster V, Rader DJ, Kathiresan S: Association of APOC3 Loss-of-Function Mutations With Plasma Lipids and Subclinical Atherosclerosis: The Multi-Ethnic BioImage Study. J Am Coll Cardiol 66(18): 2053-2055, Nov 2015.
Goth CK, Halim A, Khetarpal SA, Rader DJ, Clausen H, Schjoldager KT: A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation. Proc Natl Acad Sci U S A 112(47): 14623-14628, Nov 2015.
Nicholls SJ, Ruotolo G, Brewer HB, Kane JP, Wang MD, Krueger KA, Adelman SJ, Nissen SE, Rader DJ: Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol 66(20): 2201-2210, Nov 2015.
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Last updated: 01/27/2016
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