faculty photo

Daniel J. Rader

Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Professor
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
Education:
B.A.
Lehigh University, 1981.
M.D.
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.
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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:
8th floor Maloney Building, Hospital of The University of Pennsylvania

Selected Publications

Tuteja S, Rader DJ: High Density Lipoproteins in the Prevention of Cardiovascular Disease: Changing the Paradigm. Clin Pharmacol Ther 96(1): 48-56, Jul 2014.

Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AL: CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 370(24): 2265-2275, Jun 2014.

Yang Y, Kuwano T, Lagor WR, Albert CJ, Brenton S, Rader DJ, Ford DA, Brown RJ : Lipidomic Analyses of Female Mice Lacking Hepatic Lipase and Endothelial Lipase Indicate Selective Modulation of Plasma Lipid Species. Lipids 49(6): 505-515, Jun 2014.

Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Rader DJ, Musunuru K: Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing. Circ Res Jun 2014 Notes: Epub ahead of print.

Rosenson RS, Brewer HB, Rader DJ: Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome. Circ Res 114(12): 1880-1889, Jun 2014.

Mehta N, Qamar A, Qu L, Qasim AN, Mehta NN, Reilly MP, Rader DJ. : Differential Association of Plasma Angiopoietin-Like Proteins 3 and 4 With Lipid and Metabolic Traits. Arterioscler Thromb Vasc Biol 34(5): 1057-1063, May 2014.

Javaheri A, Rader DJ, Javaheri S: Statin therapy in heart failure: is it time for a second look? Hypertension 63(5): 909-910, May 2014.

Singh N, Jacobs F, Rader DJ, Vanhaecke J, Van Cleemput J, De Geest B: Impaired cholesterol efflux capacity and vasculoprotective function of high-density lipoprotein in heart transplant recipients. J Heart Lung Transplant 33(5): 499-506, May 2014.

Gordon AS, Tabor HK, Johnson AD, Snively BM, Assimes TL, Auer PL, Ioannidis JP, Peters U, Robinson JG, Sucheston LE, Wang D, Sotoodehnia N, Rotter JI, Psaty BM, Jackson RD, Herrington DM, O'Donnell CJ, Reiner AP, Rich SS, Rieder MJ, Bamshad MJ, Nickerson DA; NHLBI GO Exome Sequencing Project: Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset. Hum Mol Genet 23(8): 1957-1963, Apr 2014.

Lassman ME, McAvoy T, Lee A, Chappell D, Wong O, Zhou H, Reyes-Soffer G, Ginsberg HN, Millar JS, Rader DJ, Gutstein DE, Laterza O. : Practical Immunoaffinity-Enrichment LC-MS for Measuring Protein Kinetics of Low-Abundance Proteins. Clin Chem Apr 2014.

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Last updated: 07/11/2014
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