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:
Ted Panczyszyn, 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
Nicholas Hand, 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
Donna Conlon, 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
Adriaan (Onno) Holleboom, PhD
Batuhan Yenilmez
Bijun Zhao

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

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

Biostatistician:
Hanumantha (Shanker) Rao, MS
Liming Qu, MS
Wei Zhao, MS

Research Specialists:
Debbie Cromley
Edwige Edouard
Susannah Elwyn, MS
Stacey Lytle
Mayda Hernandez, MS
Phyllis May
Mary McCoy, PhD
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
Maria Escobar
James McParland
Sharon Molino
Tracey Sikora
Masako Ueda, MD

Selected Publications

Millar JS, Reyes-Soffer G, Jumes P, Dunbar RL, deGoma EM, Baer AL, Karmally W, Donovan DS, Rafeek H, Pollan L, Tohyama J, Johnson-Levonas AO, Wagner JA, Holleran S, Obunike J, Liu Y, Ramakrishnan R, Lassman ME, Gutstein DE, Ginsberg HN, Rader DJ. : Anacetrapib lowers LDL by increasing ApoB clearance in mildly hypercholesterolemic subjects. J Clin Invest 125(6): 2510-2522, Jun 2015.

428. Stefanutti C, Blom DJ, Averna MR, Meagher EA, Theron HD, Marais AD, Hegele RA, Sirtori CR, Shah PK, Gaudet D, Vigna GB, Sachais BS, Di Giacomo S, du Plessis AM, Bloedon LT, Balser J, Rader DJ, Cuchel M; Phase 3 HoFH Lomitapide Study Investigators. : The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - A post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis 240(2): 408-414, Jun 2015.

Zhang H, Xue C, Shah R, Bermingham K, Hinkle CC, Li W, Rodrigues A, Tabita-Martinez J, Millar JS, Cuchel M, Pashos E, Liu Y, Yan R, Yang W, Gosai SJ, VanDorn D, Chou S, Gregory BD, Morrisey E, Li M, Rader DJ, Reilly MP: Functional Analysis and Transcriptomic Profiling of iPSC-Derived Macrophages and Their Application in Modeling Mendelian Disease. Circ Res 117(1): 17-28, Jun 2015.

Agarwala AP, Rodrigues A, Risman M, McCoy M, Trindade K, Qu L, Cuchel M, Billheimer J, Rader DJ. : High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease. Arterioscler Thromb Vasc Biol 35(6): 1515-1519, Jun 2015.

431. Qamar A, Khetarpal SA, Khera AV, Qasim A, Rader DJ, Reilly MP: Plasma Apolipoprotein C-III Levels, Triglycerides, and Coronary Artery Calcification in Type 2 Diabetics. Arterioscler Thromb Vasc Biol Jun 2015 Notes: [Epub ahead of print]

430. Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, Rader DJ, Brewer HB, Barter PJ. : Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Jun 2015 Notes: [Epub ahead of print]

Luthi AJ, Lyssenko NN, Quach D, McMahon KM, Millar JS, Vickers KC, Rader DJ, Phillips MC, Mirkin CA, Thaxton CS: Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high-density lipoprotein. J Lipid Res 56(5): 972-985, May 2015.

Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, Lukmanova D, Mucksavage ML, Luben R, Billheimer J, Kastelein JJ, Boekholdt SM, Khaw KT, Wareham N, Rader DJ. : Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol. May 2015 Notes: [Epub ahead of print]

deGoma EM, Salavati A, Shinohara RT, Saboury B, Pollan L, Schoen M, Torigian DA, Mohler ER, Dunbar RL, Litt HI, Woo J, Rader DJ, Alavi A, Mehta NN.: A Pilot Trial to Examine the Effect of High-Dose Niacin on Arterial Wall Inflammation Using Fluorodeoxyglucose Positron Emission Tomography. Acad Radiol 22(5): 600-609, May 2015.

Rader DJ: Human genetics of atherothrombotic disease and its risk factors. Arterioscler Thromb Vasc Biol 35(4): 741-747, Apr 2015.

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Last updated: 06/22/2015
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