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

Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. : Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc 5(9): 407-416, Sep 2016.

Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT, Lorenzato C, Pordy R, Stroes E. : Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher. Cardiovasc Drugs Ther Sep 2016 Notes: Epub ahead of print.

Saleheen D, Rader DJ, Voight BF: Disentangling the Causal Association of Plasma Lipid Traits and Type 2 Diabetes Using Human Genetics. JAMA Cardiol Aug 2016 Notes: Epub ahead of print.

Mansouri B, Kivelevitch D, Natarajan B, Joshi AA, Ryan C, Benjegerdes K, Schussler JM, Rader DJ, Reilly MP, Menter A, Mehta NN. : Comparison of Coronary Artery Calcium Scores Between Patients With Psoriasis and Type 2 Diabetes. JAMA Dermatol Aug 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 36(8): 1038-1047, Aug 2016.

Khetarpal SA, Schjoldager KT, Christoffersen C, Raghavan A, Edmondson AC, Reutter HM, Ahmed B, Ouazzani R, Peloso GM, Vitali C, Zhao W, Somasundara AV, Millar JS, Park Y, Fernando G, Livanov V, Choi S, Noé E, Patel P, Ho SP; Myocardial Infarction Exome Sequencing Study, Kirchgessner TG, Wandall HH, Hansen L, Bennett EP, Vakhrushev SY, Saleheen D, Kathiresan S, Brown CD, Abou Jamra R, LeGuern E, Clausen H, Rader DJ. : Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents. Cell Metab 24(2): 234-245, Aug 2016.

Beheshtian A, Shitole SG, Segal AZ, Leifer D, Tracy RP, Rader DJ, Devereux RB, Kizer JR : Lipoprotein (a) level, apolipoprotein (a) size, and risk of unexplained ischemic stroke in young and middle-aged adults. Atherosclerosis 253: 47-53, Aug 2016 Notes: Epub ahead of print.

Javaheri A, Molina M, Zamani P, Rodrigues A, Novak E, Chambers S, Stutman P, Maslanek W, Williams M, Lilly SM, Heeger P, Sayegh MH, Chandraker A, Briscoe DM, Daly KP, Starling R, Ikle D, Christie J, Rame JE, Goldberg LR, Billheimer J, Rader DJ : Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant Jul 2016 Notes: Epub ahead of print.

Daugherty A, Hegele RA, Mackman N, Rader DJ, Schmidt AM, Weber C: Complying With the National Institutes of Health Guidelines and Principles for Rigor and Reproducibility: Refutations. Arterioscler Thromb Vasc Biol 36(7): 1303-1304, Jul 2016.

Patel AP, Peloso GM, Pirruccello JP, Johansen CT, Dubé JB, Larach DB, Ban MR, Dallinge-Thie GM, Gupta N, Boehnke M, Abecasis GR, Kastelein JJ, Hovingh GK, Hegele RA, Rader DJ, Kathiresan S : Targeted exonic sequencing of GWAS loci in the high extremes of the plasma lipids distribution. Atherosclerosis 250: 63=68, Jul 2016.

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Last updated: 09/22/2016
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