faculty photo

Daniel J. Rader

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.
Permanent link

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

Millar JS, Reyes-Soffer G, Jumes P, Dunbar RL, deGoma EM, Baer AL, Karmally W, Donovan DS, Rafeek H, Pollan L, Tohyama J, Johnson-Levonas AO, Wagner JA, Holleran S, Obunike J, Liu Y, Ramakrishnan R, Lassman ME, Gutstein DE, Ginsberg HN, Rader DJ. : Anacetrapib lowers LDL by increasing ApoB clearance in mildly hypercholesterolemic subjects. J Clin Invest 125(6): 2510-2522, Jun 2015.

428. Stefanutti C, Blom DJ, Averna MR, Meagher EA, Theron HD, Marais AD, Hegele RA, Sirtori CR, Shah PK, Gaudet D, Vigna GB, Sachais BS, Di Giacomo S, du Plessis AM, Bloedon LT, Balser J, Rader DJ, Cuchel M; Phase 3 HoFH Lomitapide Study Investigators. : The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - A post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis 240(2): 408-414, Jun 2015.

Zhang H, Xue C, Shah R, Bermingham K, Hinkle CC, Li W, Rodrigues A, Tabita-Martinez J, Millar JS, Cuchel M, Pashos E, Liu Y, Yan R, Yang W, Gosai SJ, VanDorn D, Chou S, Gregory BD, Morrisey E, Li M, Rader DJ, Reilly MP: Functional Analysis and Transcriptomic Profiling of iPSC-Derived Macrophages and Their Application in Modeling Mendelian Disease. Circ Res 117(1): 17-28, Jun 2015.

Agarwala AP, Rodrigues A, Risman M, McCoy M, Trindade K, Qu L, Cuchel M, Billheimer J, Rader DJ. : High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease. Arterioscler Thromb Vasc Biol 35(6): 1515-1519, Jun 2015.

431. 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 Jun 2015 Notes: [Epub ahead of print]

430. Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, Rader DJ, Brewer HB, Barter PJ. : Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Jun 2015 Notes: [Epub ahead of print]

Luthi AJ, Lyssenko NN, Quach D, McMahon KM, Millar JS, Vickers KC, Rader DJ, Phillips MC, Mirkin CA, Thaxton CS: Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high-density lipoprotein. J Lipid Res 56(5): 972-985, May 2015.

Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, Lukmanova D, Mucksavage ML, Luben R, Billheimer J, Kastelein JJ, Boekholdt SM, Khaw KT, Wareham N, Rader DJ. : Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol. May 2015 Notes: [Epub ahead of print]

deGoma EM, Salavati A, Shinohara RT, Saboury B, Pollan L, Schoen M, Torigian DA, Mohler ER, Dunbar RL, Litt HI, Woo J, Rader DJ, Alavi A, Mehta NN.: A Pilot Trial to Examine the Effect of High-Dose Niacin on Arterial Wall Inflammation Using Fluorodeoxyglucose Positron Emission Tomography. Acad Radiol 22(5): 600-609, May 2015.

Rader DJ: Human genetics of atherothrombotic disease and its risk factors. Arterioscler Thromb Vasc Biol 35(4): 741-747, Apr 2015.

back to top
Last updated: 10/02/2015
The Trustees of the University of Pennsylvania