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:
9th 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:
Michael S. Kelly, 215-573-1264


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

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


Research Group:

Research Associate Professors:
Marina Cuchel, MD PhD

Research Assistant Professors:
Yanqing (Anna) Gong, PhD
Nicholas Hand, PhD

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

Senior Research Investigators:
Jeffrey Billheimer, PhD
John Millar, PhD
Athanasia (Nancy) Skoura, PhD

Research Associates:
Nicholas Lyssenko, PhD
Sony Tuteja, PharmD

Post-doctoral Fellows:
Deepti Abbey, PhD
Ezimamaka Ajufo, MD
Robert Bauer, PhD
Xin Bi, PhD
Donna Conlon, PhD
Marie Guerraty, MD/PhD
Ali Javaheri, MD/PhD
Sylvia Nürnberg, PhD
Evanthia Pashos, PhD
Swapnil Shewale, PhD

Doris Duke Fellow:
Aeron Small

Visiting Scientists:
Jian Cui, MD
Marjolein van den Boogert
Bijun Zhao

Graduate Students:
Devin Christopher
Sumeet Khetarpal
Hye In Kim
Wen Lin
Minal Mehta
Cecilia Vitali
Christopher Yu

Project Managers:
Stephanie DerOhannessian, MB
Dawn Marchadier, MS

Bioinformatician:
H. Shanker Rao, MS

Biostatisticians:
Wei Zhao, MS
Jung-Jin Lee

Data Analyst:
Khalif Coaxum

Research Specialists:
Debra Cromley
Edwige Edouard
Susannah Elwyn, MS
Mayda Hernandez, MS
James McParland
Linda Morrell
Amrith Rodrigues, MS
Mikhaila Smith
Maosen Sun, MD/PhD
Teo Tran
Kevin Trindade
Aisha Wilson, MLAS


Clinical Research Personnel:

Project Managers:
Amanda Baer, MB MBA

Data Coordinators:
Marjorie Risman, MS

Clinical Research Coordinators:
Canita Brent
Maria Escobar
Polina Ferd
Dusanka Lalic
Karen Monono
Anna Sicilia
Tracey Sikora
Karen Terembula
Masako Ueda, MD
Rahma Warsi

Clinical Research Assistants:
Muhamad Farhan
Jamila Hoque
Lauren Vincent
Laura Walters
Katy Wong

Selected Publications

Wolf JH, Holmes MV, Fouraschen S, Keating BJ, Baker T, Emond J, Rader DJ, Shaked A, Olthoff KM: Serum lipid expression correlates with function and regeneration following living donor liver transplantation. Liver Transpl 22(1): 103-101, Jan 2016.

Kastelein JJ, Nissen SE, Rader DJ, Hovingh GK, Wang MD, Shen T, Krueger KA: Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study. Eur Heart J. Jan 2016 Notes: Epub ahead of print

Ibrahim S, Somanathan S, Billheimer J, Wilson JM, Rader DJ : Stable Liver-specific Expression of Human IDOL in Humanized Mice Raises Plasma Cholesterol. Cardiovasc Res. Jan 2016 Notes: Epub ahead of print.

Herzog E, Pragst I, Waelchli M, Gille A, Schenk S, Mueller-Cohrs J, Diditchenko S, Zanoni P, Cuchel M, Seubert A, Rader DJ, Wright SD: Reconstituted high-density lipoprotein can elevate plasma alanine aminotransferase by transient depletion of hepatic cholesterol: role of the phospholipid component. J Appl Toxicol. Dec 2015 Notes: Epub ahead of print.

Voight BF, Rader DJ: Human genetics shines a light on ischaemic stroke. Lancet Neurol. Dec 2015 Notes: Epub ahead of print.

Khera AV, Millar JS, Ruotolo G, Wang MD, Rader DJ : Potent peroxisome proliferator-activated receptor-α agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome. Eur Heart J 36(42): 3020-3022, Nov 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 35(11): 2269-2268, Nov 2015.

Natarajan P, Kohli P, Baber U, Nguyen KD, Sartori S, Reilly DF, Mehran R, Muntendam P, Fuster V, Rader DJ, Kathiresan S: Association of APOC3 Loss-of-Function Mutations With Plasma Lipids and Subclinical Atherosclerosis: The Multi-Ethnic BioImage Study. J Am Coll Cardiol 66(18): 2053-2055, Nov 2015.

Goth CK, Halim A, Khetarpal SA, Rader DJ, Clausen H, Schjoldager KT: A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation. Proc Natl Acad Sci U S A 112(47): 14623-14628, Nov 2015.

Nicholls SJ, Ruotolo G, Brewer HB, Kane JP, Wang MD, Krueger KA, Adelman SJ, Nissen SE, Rader DJ: Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol 66(20): 2201-2210, Nov 2015.

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Last updated: 01/27/2016
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