Daniel J. Rader

faculty photo
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
Education:
B.A.
Lehigh University, 1981.
M.D.
Medical College of Pennsylvania, 1984.
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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

Rader DJ: Spotlight on HDL biology: new insights in metabolism, function, and translation. Cardiovasc Res. 103(3): 337-340, Aug 2014.

Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Cowan CA, Rader DJ, Musunuru K. : Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing. Circ Res. 115(5): 488-492, Aug 2014.

Anthanont P, Polisecki E, Asztalos BF, Diffenderfer MR, Barrett PH, Millar JS, Billheimer J, Cuchel M, Rader DJ, Schaefer EJ: A novel ApoA-I truncation (ApoA-IMytilene) associated with decreased ApoA-I production. Atherosclerosis 235(2): 470-476, Aug 2014.

398. Mehta NN, Matthews GJ, Krishnamoorthy P, Shah R, McLaughlin C, Patel P, Budoff M, Chen J, Wolman M, Go A, He J, Kanetsky PA, Master SR, Rader DJ, Raj D, Gadegbeku CA, Shah R, Schreiber M, Fischer MJ, Townsend RR, Kusek J, Feldman HI, Foulkes AS, Reilly MP; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators.: Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study. Eur Heart J. 14(35): 2115 - 2122, Aug 2014.

Somanathan S, Jacobs F, Wang Q, Hanlon AL, Wilson JM, Rader DJ.: AAV Vectors Expressing LDLR Gain-of-Function Variants Demonstrate Increased Efficacy in Mouse Models of Familial Hypercholesterolemia. Circ Res. Jul 2014 Notes: [Epub ahead of print]

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.

Rahman M, Yang W, Akkina S, Alper A, Anderson AH, Appel LJ, He J, Raj DS, Schelling J, Strauss L, Teal V, Rader DJ; CRIC Study Investigators. : Relation of Serum Lipids and Lipoproteins with Progression of CKD: The CRIC Study. Clin J Am Soc Nephrol 9(7): 1190-1198, 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.

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.

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Last updated: 09/23/2014
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