ITMAT Home » Daniel J. Rader, M.D.

Daniel J. Rader, M.D.

Education

1981B.A.Lehigh University
1984M.D.Medical College of Pennsylvania

Research Summary:

Dr. Rader’s laboratory and research program is focused on genetic and inflammatory factors that regulate the metabolism and function of plasma lipoproteins and their interaction with the vessel wall in promoting and inhibiting atherogenesis and on translational approaches to novel therapies for lipid disorders and atherosclerosis. A variety of basic cell and molecular laboratory techniques, mouse models, and clinical research approaches are used in addressing these questions. Some of the major ongoing projects are:

  1. The role of extracellular lipases as important physiologic and pathophysiologic regulators of lipoprotein metabolism and function whose expression is both genetically determined and influenced by inflammatory factors. We have cloned several new members of the lipoprotein lipase gene family and are investigating their function and regulation.
  2. Molecular and cellular mechanisms by which HDL-associated proteins inhibit atherogenesis and induce regression of atherosclerotic lesions. Somatic gene transfer of HDL-associated proteins is used in mouse models of Atherosclerosis in order to study their effects on atherogenesis in vivo. Tissue culture models have been developed in order to reconstruct cellular aspects of the atherosclerotic process in vitro and determine anti-inflammatory effects of HDL proteins.
  3. Dietary and genetic regulation of hepatic lipoprotein production. Gene transfer, transgenic, and cell culture approaches are used to study the interaction between specific genes, such as the microsomal transfer protein and diacylglycerol acyltransferase, and dietary manipulation in the regulation of hepatic apoB production in mice. Lipoprotein kinetic studies are also performed in humans using endogenous labeling of apolipoproteins with stable isotopically labeled leucine.
  4. Genetic factors associated with premature atherosclerotic disease and high or low levels of HDL cholesterol. Subjects with family history of premature coronary disease or with extremes of HDL cholesterol are recruited and phenotyped for cardiovascular risk factors and clinical and subclinical Atherosclerosis. Candidate genes are investigated for their association with subclinical Atherosclerosis or variation in HDL cholesterol levels and linkage analysis of sib pairs and large pedigrees will be performed.
  5. Novel therapeutic approaches to lipid disorders and Atherosclerosis. We are involved in translational proof-of-concept studies in animals and humans of novel approaches to raising HDL cholesterol, improving HDL function, and reducing atherogenic lipoproteins. The overall focus of our research effort is basic cell and molecular laboratory science with translation into animal experiments and ultimately into patient-oriented research in the areas of lipoprotein metabolism and premature Atherosclerosis.

Selected Key Publications:

  • Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, Li X, Kumaravel A, Wang MY, Ai D, Guo L, Alexander ET, Nguyen D, Lund-Katz S, Phillips MC, Morales CR, Tall AR, Kathiresan S, Fisher EA, Musunuru K, Rader DJ.  Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism.  J Clin Invest. 2012 Aug 1;122(8):2807-16
  • Khetarpal SA, Edmondson AC, Raghavan A, Neeli H, Jin W, Badellino KO, Demissie S, Manning AK, DerOhannessian SL, Wolfe ML, Cupples LA, Li M, Kathiresan S, Rader DJ.  Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol.  PLoS Genet. 2011 Dec;7(12):e1002393.
  • Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, …, Kathiresan S, Samani NJ, Epstein SE, Rader DJ. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011 ;377(9763):383-92. PMID: 21239051
  • Khera AV*, Cuchel M*, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky R, Mohler ER, Rothblat GH, Rader DJ.  Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.  N Engl J Med (2011) 364:12-20
  • Burkhardt R*, Toh S*, Lagor WR, Birkeland A, Levin M, Li X, Robblee M, Fedorov VD, Yamamoto M, Satoh T, Akira S, Kathiresan S, Breslow JL* and Rader DJ*.  Trib1, a novel lipid and myocardial infarction associated gene, regulates hepatic lipogenesis and VLDL production in mice.  J Clin Invest (2010) 120(12):4410-4  PMID: 21084752
  • Musunuru K*, Strong A*, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JJ, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S*, Rader DJ*.   From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus.  Nature (2010) Aug 5;466(7307):714-9 PMID: 20686566
  • Teslovich TM*, Musunuru K*, Smith AV, Edmondson AC, Stylianou IM, …  Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Holm H, Reilly MP, Samani NJ, Schunkert H, Cupples LA*, Sandhu MS*, Ridker PM*, Rader DJ*, van Duijn CM*, Peltonen L*, Abecasis GR*, Boehnke M*, Kathiresan S*.  Biological, Clinical, and Population Relevance of 95 Loci Mapped for Serum Lipid Concentrations.  Nature (2010) Aug 5;466(7307):707-13 PMID: 20686565
  • Cuchel M, Lund-Katz S, de la Llera-Moya M, Millar JS, Chang D, Fuki I, Rothblat GH, Phillips MC, Rader DJ. Pathways by which reconstituted high-density lipoprotein mobilizes free cholesterol from whole body and from macrophages.  Arterioscler Thromb Vasc Biol 30(3):526-32 (2009) PMID: 20018934
  • Griffon N, Jin W, Petty TJ, Millar J, Badellino KO, Saven JG, Marchadier DH, Kempner ES, Billheimer J, Glick JM, Rader DJ. Identification of the active form of endothelial lipase, a homodimer in a head-to-tail conformation. J Biol Chem 284(35):23322-30 (2009) PMID: 19567873
  • Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, Jensen MK, Rimm EB, Wang J, Rodrigues A, Bamba V, Khetarpal SA, Wolfe ML, DerOhannessian S, Li M, Reilly MP, Aberle J, Evans D, Hegele RA, Rader DJ.  Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans.  J Clin Inves 119(4):1042-50 (2009) PMID: 19287092
  • Badellino KO, Wolfe ML, Reilly MP, Rader DJ. Endothelial lipase is increased in vivo by inflammation in humans. Circulation 117:678-85 (2008) PMID: 18212282
  • Tanigawa H, Billheimer JT, Tohyama J, Zhang Y, Rothblat G, Rader DJ. Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport. Circulation 116:1267-73 (2007) PMID: 17709636
  • Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 117:2216-2224 (2007) PMID: 17657311
  • Jin W, Wang X, Millar JS, Quertermous T, Rothblat GH, Glick JM, Rader DJ. Hepatic Proprotein Convertases Modulate HDL Metabolism. Cell Metab 6:129-136 (2007) PMID: 17681148
  • Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ.  Inhibition of microsomal triglyceride transfer protein in homozygous familial hypercholesterolemia.  New Engl J Med 356:148-156 (2007) PMID: 17215532

 

Awards, Honors, Membership in Honorary Societies:

Election to Institute of Medicine (2011)
Associate Editor, Journal of Clincial Investigation (2007)
International Atherosclerosis Society Distinguished Fellow (2007)
Election to Association of American Physicians (2007)
Bristol Myers Squibb “Freedom to Discover” Unrestricted Cardiovascular Research Grant (2005)
Cooper McClure Chair Professorship, University of Pennsylvania School of Medicine (2005)
William Osler Patient Oriented Research Award, University of Pennsylvania School of Medicine (2005)
Gill Heart Institute Award for Outstanding Contributions to Cardiovascular Research (2005)
Jeffrey M. Hoeg Award for Basic Science and Clinical Research, Arteriosclerosis, Thrombosis, and Vascular Biology Council of the American Heart Association (2005)
Doris Duke Charitable Foundation Distinguished Clinical Scientist Award (2002)
Listing in “Top Doctors of Philadelphia” Philadelphia Magazine (2002 – 2005)
Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (2000)
Established Investigator, American Heart Association (2000)
Election to American Society of Clinical Investigation (1999)
Donald B. Martin Outstanding Teacher Award (1997)
Outstanding Faculty Award, Department of Medicine (1996)
WW Smith Charitable Trust Awardee (1995)
Dean's Award, Medical College of Pennsylvania (1984)
Alpha Omega Alpha (1983)
Phi Beta Kappa (1979)

Editorial Board Memberships:

Editorial Board, Journal of Clinical Investigation (2007-present)
Editorial Board, Journal of Lipid Research (2005-present)
Editorial Board, Circulation Research (2002-present)
Editorial Board, Circulation (2002-present)
Editorial Board, American Journal of Physiology (Endocrinology and Metabolism) (2001-present)
Editorial Board, Arteriosclerosis, Thrombosis, and Vascular Biology (2000-present)
Editorial Board, Trends in Molecular Medicine (1999-present)

Laboratory and Clinical Personnel:

Name Position Telephone Email Address
Bauer, Rob Postdoctoral Fellow 215-898-5909 rcbauer@mail.med.upenn.edu
Billheimer, Jeff Sr. Research Investigator 215-746-0237 billheij@mail.med.upenn.edu
Christopher, Devin Graduate Student 215-573-7666 devc@mail.med.upenn.edu
Cromley, Debra Research Specialist 215-898-5909 dcromley@mail.med.upenn.edu
Cuchel, Marina Research Assistant Professor 215-746-2834 mcuchel@mail.med.upenn.edu
DerOhannessian, Stephanie Project Manager 215-746-6402 srestine@mail.med.upenn.edu
Doveikis, Julia Research Specialist 215-746-6403 doveikis@mail.med.upenn.edu
Edouard, Edwige Research Specialist 215-573-7666 edwige2@mail.med.upenn.edu
Enriquez, Maria Research Specialist 215-746-4666 mariaenriquez08@gmail.com
Khetarpal, Sumeet  MD/PhD Student 215-746-6403 sumeetak@mail.med.upenn.edu
Kim, Hyein Rotating PhD Student 215-746-6403 Ihye@mail.med.upenn.edu
Kuwano, Takashi  Postdoctoral Fellow 215-573-7666 tkuwano@upenn.edu
Lagor, William Research Associate 215-573-5746 wlagor@mail.med.upenn.edu
Lin, Wen PhD Student 215-573-7666 linwen@mail.med.upenn.edu
Long, Shiyin Visiting Scholar 215-573-7666 shiyinlo@upenn.edu
Lukmanova-Kegelman, Daniya Research Specialist 215-898-5909 daniya@mail.med.upenn.edu
Marchadier, Dawn Project Manager 215-573-7534 vista@mail.med.upenn.edu
May, Phyllis Research Specialist 215-746-6403 plmay@mail.med.upenn.edu
McCoy, Mary Research Assistant  215-898-5909 mmccoy@neumann.edu
Mehta, Minal PhD Student 215-746-6403 mimehta@mail.med.upenn.edu
Millar, John Sr. Research Investigator 215-898-0638 jsmillar@mail.med.upenn.edu
Morrell, Linda Research Specialist 215-573-4121 lmorrell@mail.med.upenn.edu
Mucksavage, Megan Project Manager 215-746-0358 mewolfe@mail.med.upenn.edu
Pashos, Evanthia Postdoctoral Fellow 215-898-5909 evpashos@mail.med.upenn.edu
Patel, Kevin PhD Student 215-573-7666 kevinmpatel@gmail.com
Picataggi, Antonino Research Specialist 215-898-5909 apicci@gmail.com
Qu, Liming Biostatistician 215-746-3886 qui@mail.med.upenn.edu
Rader, Dan Principal Investigator 215-573-4176 rader@mail.med.upenn.edu
Redon, Valeska Research Specialist 215-898-6955 valeska@mail.med.upenn.edu
Rodrigues, Amrith Research Specialist 215-898-5909 amrith@mail.med.upenn.edu
Saleheen, Danish Research Associate 215-573-6323 saleheen@mail.med.upenn.edu
Strong, Alanna MD/PhD Student 215-746-6403 astrong@mail.med.upenn.edu
Sun, Maosen Research Specialist 215-573-7666 maosen@mail.med.upenn.edu
Tohyama, Junichiro Postdoctoral Fellow 215-746-6403 junichi2@mail.med.upenn.edu
Trindade, Kevin Research Specialist 215-746-6403 kevintri@mail.med.upenn.edu
Tuteja, Sony Postdoctoral Fellow 215-573-7834 sony.tuteja@gmail.com
Wilson, Aisha Research Specialist 215-573-7666 faruqi@mail.med.upenn.edu
Zanoni, Paolo Postdoctoral Fellow 215-573-7666 paolo.zanoni2@studio.unibo.it
Zhaow, Wei Jr. Biostatistician 215-898-9332 zhaowei1@mail.med.upenn.edu>
Administration
Carmichael, Linda Administrative Assistant 215-573-4176 lincarm@upenn.edu
Nagelberg, Jonathan Business Administrator / Grants Manager 215-573-1264  jnage@upenn.edu
Warford, Cathy Executive Assistant 215-743-7272 cwarford@mail.med.upenn.edu
       
Lab Fax   215-573-8606  

 

 

Research Lab Address:

11th Floor Smilow Center for Translational Research
University of Pennsylvania
3400 Civic Center Blvd, Bldg 421
Philadelphia, PA 19104-5158

Clinical Research Lab Address:

East Pavilion, 2nd Floor
Perelman Center for Advanced Medicine
University of Pennsylvania
3400 Civic Center Blvd
Philadelphia, PA 19104

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