Penn Cardiovascular Institute

Heart and Vascular Faculty

faculty photo

Daniel J. Rader, M.D.

Seymour Gray Professor of Molecular Medicine
Department: Medicine

Contact information
Perelman School of Medicine
University of Pennsylvania
11-125 Smilow Center for Translational Research
3400 Civic Center Blvd
Philadelphia, PA 19104-5158
Office: (215) 573-4176
Fax: (215) 573-8606
Lehigh University, 1981.
Medical College of Pennsylvania, 1984.
Post-Graduate Training
Internship, Internal Medicine, Yale-New Haven Hospital, New Haven, CT, 1984-1985.
Residency, Internal Medicine, Yale-New Haven Hospital, New Haven, CT, 1985-1987.
Chief Resident, Internal Medicine, Yale School of Medicine, New Haven, CT, 1987-1988.
Medical Staff Fellow, Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, 1988-1991.
American Board of Internal Medicine, 1987.
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Description of Research Expertise

Research Interests
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

Research Lab:
11th floor, Smilow Center for Translational Research

Clinical Research:
9th floor Maloney Building, Hospital of The University of Pennsylvania

Selected Publications

CARDIoGRAMplusC4D Consortium.: A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 47(10): 1121-1130, Oct 2015.

Guo Y, Fan Y, Zhang J, Lomberk GA, Zhou Z, Sun L, Mathison AJ, Garcia-Barrio MT, Zhang J, Zeng L, Li L, Pennathur S, Willer CJ, Rader DJ, Urrutia R, Chen YE.: Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production. J Clin Invest. 125(10): 3819-3830, Oct 2015.

Bauer RC, Sasaki M, Cohen DM, Cui J, Smith MA, Yenilmez BO, Steger DJ, Rader DJ.: Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPa. J Clin Invest. 125(10): 3809-3818, Oct 2015.

Rader DJ.: Lysosomal Acid Lipase Deficiency - A New Therapy for a Genetic Lipid Disease. N Engl J Med. 373(11): 1071-1073, Sep 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. Sep 2015 Notes: [Epub ahead of print]

Khera AV, Qamar A, Murphy SA, Cannon CP, Sabatine MS, Rader DJ. : On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study). Am J Cardiol. 116(5): 694-698, Sep 2015.

Iqbal J, Walsh MT, Hammad SM, Cuchel M, Tarugi P, Hegele RA, Davidson NO, Rader DJ, Klein RL, Hussain MM. : Microsomal triglyceride transfer protein transfers and determines plasma concentrations of ceramide and sphingomyelin, but not glycosylceramide. J Biol Chem. Sep 2015 Notes: [Epub ahead of print]

Peloso GM, Rader DJ, Gabriel S, Kathiresan S, Daly MJ, Neale BM.: Phenotypic extremes in rare variant study designs. Eur J Hum Genet. Sep 2015 Notes: [Epub ahead of print]

Shah R, Matthews GJ, Shah RY, McLaughlin C, Chen J, Wolman M, Master SR, Chai B, Xie D, Rader DJ, Raj DS, Mehta NN, Budoff M, Fischer MJ, Go AS, Townsend RR, He J, Kusek JW, Feldman HI, Foulkes AS, Reilly MP; CRIC Study Investigators. : Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 66(2): 266-273, Aug 2015.

Qamar A, Khetarpal SA, Khera AV, Qasim A, Rader DJ, Reilly MP: Plasma Apolipoprotein C-III Levels, Triglycerides, and Coronary Artery Calcification in Type 2 Diabetics. Arterioscler Thromb Vasc Biol 35(8): 1880-1888, Aug 2015.

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Last updated: 10/20/2015
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