Daniel
 
J.
 
Rader
M.D.
Email: 
rader@mail.med.upenn.edu
Address: 
Perelman School of Medicine University of Pennsylvania 11-125 Smilow Center for Translational Research 3400 Civic Center Blvd
(215) 573-4176
Affiliations
Affiliations
Centers and Programs:
Clinical and Translational Research Center (CTRC)
Expertise

Penn CVI Scientific Director for Translational / Clinical Research

CVI Program Unit Administrator (Director):
Prevention / Atherosclerosis / Lipids

Research Interests
Genetic regulation of lipid and lipoprotein metabolism and molecular relationship to atherosclerosis.

Description of Research
My laboratory is interested in genetic and inflammatory factors that regulate the metabolism and function of plasma lipoproteins and their interaction with the vessel wall in promoting and
inhibiting atherogenesis. A variety of basic cell and molecular laboratory techniques, mouse models, and clinical research approaches are used in addressing these questions.

Some of the major ongoing projects are:
1) Inflammatory and genetic factors that regulate the in vivo metabolism of HDL and other lipoproteins. A major current focus is that extracellular lipases are important physiologic and pathophysiologic regulators of lipoprotein metabolism and function and that their expression is both genetically determined and influenced by inflammatory factors. We have cloned several new members of the lipoprotein lipase gene family and are investigating their function and regulation.

2) Molecular and cellular mechanisms by which HDL-associated proteins inhibit atherogenesis and induce regression of atherosclerotic lesions. Somatic gene transfer of HDL-associated proteins is used in mouse models of atherosclerosis in order to study their effects on atherogenesis in vivo. Tissue culture models have been developed in order to reconstruct cellular aspects of the atherosclerotic process in vitro and determine anti-inflammatory effects of HDL proteins.

3) Dietary and genetic regulation of hepatic lipoprotein production. Gene transfer, transgenic, and cell culture approaches are used to study the interaction between specific genes, such as the microsomal transfer protein and diacylglycerol acyltransferase, and dietary manipulation in the regulation of hepatic apoB production in mice. Lipoprotein kinetic studies are also performed in humans using endogenous labeling of apolipoproteins with stable isotopically labeled leucine.

4) Genetic factors associated with premature atherosclerotic disease and high or low levels of HDL cholesterol. Subjects with family history of premature coronary disease or with extremes of HDL cholesterol are recruited and phenotyped for cardiovascular risk factors and clinical and subclinical atherosclerosis. Candidate genes are investigated for their association with subclinical atherosclerosis or variation in HDL cholesterol levels and linkage analysis of sib pairs and large pedigrees will be performed. The overall focus of our research effort is basic cell and molecular laboratory science with translation into animal experiments and ultimately into patient-oriented research in the areas of lipoprotein metabolism and premature atherosclerosis.

Rotation Projects for 2007-2008
A variety of projects involving structure-function of lipases, effects of genetic manipulation on reverse cholesterol transport and atherosclerosis in mice, human genetics of variation in HDL, and others are available.

Administrative Assistant:
Linda Watts, 215-573-4176

Research Lab:
6th floor, Biomedical Research Building (BRB) II/III

Clinical Research:
4th floor Andrew Mutch Building, Presbyterian Medical Center

Lab Personnel:

Senior Research Investigators:
Jeffrey Bilheimer, PhD
Hui Li, MD, PhD
John Millar, PhD

Assistant Professor:
Karen Badellino, RN, PhD

Research Assistant Professor:
Marina Cuchel, MD

Research Associates and Instructors:
Richard Dunbar, MD
John (Ioannis) Stylianou, PhD

Post-doctoral Fellows:
Eric Alexander, PhD
Robert Brown, PhD
William R. Lagor, PhD
Xiaoyu Li, PhD
Sue-Anne Toh, MD
Fumin Tong, PhD
Tomoyuki Yasuda, MD

Graduate Students:
Andrew C. Edmondson (MD/PhD Student)
Alanna Strong (MD/PhD Student)

Project Managers:
Amanda Baer
Dawn Marchadier, MS
Megan Mucksavage

Clinical Research Coordinators:
Annukka Bloedon
Jennifer Brazier, MS
Grace Nathanson
Marjorie Risman, MS

Research Specialists:
Debbie Cromley
Stephanie DerOhannessian
Edwige Edouard
Ermelinda Guiang
Phyllis May
Leticia Pruscino, MS
Valeska Redon
Amrith Rodrigues, MS
Mao-Sen Sun, PhD
Aisha Wilson

Visiting Scientist:
Shigenori Yamamoto, MD

Dr. Rader's studies are focused on genetic and inflammatory factors that regulate the metabolism and function of plasma lipoproteins and their interaction with the vessel wall in promoting and inhibiting atherogenesis and on translational approaches to novel therapies for lipid disorders and atherosclerosis.

Research Interests
Genetic regulation of lipid and lipoprotein metabolism and molecular relationship to atherosclerosis.

Description of Research
The Rader laboratory is interested in genetic and inflammatory factors that regulate the metabolism and function of plasma lipoproteins and their interaction with the vessel wall in promoting and inhibiting atherogenesis. A variety of basic cell and molecular laboratory techniques, mouse models, and clinical research approaches are used in addressing these questions.

Major ongoing projects include:
1) Inflammatory and genetic factors that regulate the in vivo metabolism of HDL and other lipoproteins. A major current focus is that extracellular lipases are important physiologic and pathophysiologic regulators of lipoprotein metabolism and function and that their expression is both genetically determined and influenced by inflammatory factors. We have cloned several new members of the lipoprotein lipase gene family and are investigating their function and regulation.

2) Molecular and cellular mechanisms by which HDL-associated proteins inhibit atherogenesis and induce regression of atherosclerotic lesions. Somatic gene transfer of HDL-associated proteins is used in mouse models of atherosclerosis in order to study their effects on atherogenesis in vivo. Tissue culture models have been developed in order to reconstruct cellular aspects of the atherosclerotic process in vitro and determine anti-inflammatory effects of HDL proteins.

3) Dietary and genetic regulation of hepatic lipoprotein production. Gene transfer, transgenic, and cell culture approaches are used to study the interaction between specific genes, such as the microsomal transfer protein and diacylglycerol acyltransferase, and dietary manipulation in the regulation of hepatic apoB production in mice. Lipoprotein kinetic studies are also performed in humans using endogenous labeling of apolipoproteins with stable isotopically labeled leucine.

4) Genetic factors associated with premature atherosclerotic disease and high or low levels of HDL cholesterol. Subjects with family history of premature coronary disease or with extremes of HDL cholesterol are recruited and phenotyped for cardiovascular risk factors and clinical and subclinical atherosclerosis. Candidate genes are investigated for their association with subclinical atherosclerosis or variation in HDL cholesterol levels and linkage analysis of sib pairs and large pedigrees will be performed. The overall focus of our research effort is basic cell and molecular laboratory science with translation into animal experiments and ultimately into patient-oriented research in the areas of lipoprotein metabolism and premature atherosclerosis.

Research Lab:
6th floor, Biomedical Research Building (BRB) II/III

Clinical Research:
4th floor Andrew Mutch Building, Presbyterian Medical Center

Appointments
Assistant Professor of Medicine at University of Pennsylvania School of Medicine (1994 – 2000)
Associate Professor of Medicine at University of Pennsylvania School of Medicine (2000 – 2005)
Associate Professor of Medicine in Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2004 – 2006)
Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Professor at University of Pennsylvania School of Medicine (2006– present)
Associate Professor of Pharmacology at University of Pennsylvania School of Medicine (2004 – 2006)
Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Associate Professor at University of Pennsylvania School of Medicine (2005 – 2006)
Professor of Pharmacology at University of Pennsylvania School of Medicine (2006– present)
Education
M.D., Medical College of Pennsylvania (1984)
B.A., Lehigh University (1981)
Selected Publications
Degoma EM, Rader DJ. Novel HDL-directed pharmacotherapeutic strategies.. Nature reviews. Cardiology. Vol 8(5) . 2011 May:266-277.
Potteaux S, Gautier EL, Hutchison SB, van Rooijen N, Rader DJ, Thomas MJ, Sorci-Thomas MG, Randolph GJ. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression.. The Journal of clinical investigation. Vol 121(5) . 2011 May:2025-2036.
Bauer RC, Stylianou IM, Rader DJ. Functional validation of new pathways in lipoprotein metabolism identified by human genetics.. Current opinion in lipidology. Vol 22(2) . 2011 Apr:123-8.
Mehta NN, Li M, William D, Khera AV, Derohannessian S, Qu L, Ferguson JF, McLaughlin C, Shaikh LH, Shah R, Patel PN, Bradfield JP, He J, Stylianou IM, Hakonarson H, Rader DJ, Reilly MP. The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels.. European Heart journal. Vol 32(8) . 2011 Apr:963-971.
Rak K, Rader DJ. Cardiovascular disease: the diet-microbe morbid union.. Nature. Vol 472(7341) . 2011 Apr:40-41.
Toh S-A, Millar JS, Billheimer J, Fuki I, Naik SU, Macphee C, Walker M, Rader DJ. PPAR? activation redirects macrophage cholesterol from fecal excretion to adipose tissue uptake in mice via SR-BI.. Biochemical pharmacology. Vol 81(7) . 2011 Apr:934-941.
Nijstad N, de Boer JF, Lagor WR, Toelle M, Usher D, Annema W, der Giet M van, Rader DJ, Tietge UJF. Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice.. Biochimica et biophysica acta. Vol 1811(4) . 2011 Apr:294-9.
Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, Derohannessian SL, Keating BJ, Qu L, He J, Tobin MD, Tomaszewski M, Baumert J, Klopp N, Döring A, Thorand B, Li M, Reilly MP, Koenig W, Samani NJ, Rader DJ. Dense Genotyping of Candidate Gene Loci Identifies Variants Associated With High-Density Lipoprotein Cholesterol.. Circulation. Vol 4(2) . 2011 Apr:145-155.
Magge SN, Stettler N, Koren D, Levitt Katz LE, Gallagher PR, Mohler ER 3rd, Rader DJ.. Adiponectin Is Associated with Favorable Lipoprotein Profile, Independent of BMI and Insulin Resistance, in Adolescents.. J Clin Endocrinol Metab. Vol 96(5) . 2011 May:1549-1554.