Daniel J. Rader

faculty photo
Seymour Gray Professor of Molecular Medicine
Director, Preventive Cardiovascular Medicine and Lipid Clinic, University of Pennsylvania Health System
Associate Director, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine
Director, Cardiovascular Metabolism Unit, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine
Program Director, General Clinical Research Center, University of Pennsylvania Medical Center
Bridge Funding Program Committee, Perelman School of Medicine at the University of Pennsylvania
Committee on Appointments and Promotions, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania
Scientific Director, Clinical and Translational Research, Cardivascular Institute, Perelman School of Medicine at the University of Pennsylvania
Chief, Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania
Director, PennMedicine BioBank, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine
Chair, Department of Genetics, Perelman School of Medicine at The University of Pennsylvania
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

Description of Itmat 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


Administrative Assistant:
Linda Carmichael, 215-573-4176

Executive Assistant:
Cathy Warford, 215-573-7272

Grants Manager:
Jonathan Nagelberg, 215-573-1264


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

Clinical Research:
8th floor Maloney Building, Hospital of The University of Pennsylvania


Lab Personnel:

Research Assistant Professors:
Marina Cuchel, MD/PhD
Yanqing (Anna) Gong, PhD

Adjunct Professors:
Sissel Lund-Katz, PhD
Michael C. Phillips, PhD

Senior Research Investigators:
Jeffrey Bilheimer, PhD
John Millar, PhD

Research Associates:
Salam Ibrahim, PhD
Nicholas Lyssenko, PhD
Sony Tuteja, PharmD

Post-doctoral Fellows:
Robert Bauer, PhD
Xin Bi, PhD
Marie Guerraty, MD/PhD
Ali Javaheri, MD/PhD
Sylvia N├╝rnberg, PhD
Evanthia Pashos, PhD
Junichiro Tohyama, MD/PhD

Visiting Scientists:
Jian Cui, MD
Hongyu (Angela) Han, PhD

Graduate Students:
Devin Christopher
Sumeet Khetarpal
HyeIn (Lucy) Kim
Wen Lin
Minal Mehta
Kevin Patel
Christopher Yu

Project Managers:
Stephanie DerOhannessian, MS
Dawn Marchadier, MS
Megan Mucksavage, MTR

Biostatistician:
Liming Qu, MS
Wei Zhao, MS

Research Specialists:
Debbie Cromley
Edwige Edouard
Susannah Elwyn, MS
Daniya Lukmanova, MS
Stacey Lytle
Mayda Hernandez MS
Phyllis May
Linda Morrell
Antonino Picataggi
Amrith Rodrigues, MS
Mikhaila Smith
Mao-Sen Sun, MD/PhD
Kevin Trindade
Aisha Wilson MLAS


Clinical Research Personnel:

Project Managers:
Amanda Baer, MBA

Data Coordinators:
Marjorie Risman, MS

Clinical Research Coordinators:
Canita Brent
Fiona Devotta
Maria Escobar
Sharon Molino
Marisa Schoen
Tracey Sikora

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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