Daniel J. Rader, M.D.
Education
| 1981 | B.A. | Lehigh University |
| 1984 | M.D. | Medical College of Pennsylvania |
Research Summary:
Dr. Rader’s laboratory and research program is 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. 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:
- The role of extracellular lipases as important physiologic and pathophysiologic regulators of lipoprotein metabolism and function whose 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.
- 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.
- 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.
- 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.
- Novel therapeutic approaches to lipid disorders and Atherosclerosis. We are involved in translational proof-of-concept studies in animals and humans of novel approaches to raising HDL cholesterol, improving HDL function, and reducing atherogenic lipoproteins. 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.
Selected Key Publications:
- Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, Li X, Kumaravel A, Wang MY, Ai D, Guo L, Alexander ET, Nguyen D, Lund-Katz S, Phillips MC, Morales CR, Tall AR, Kathiresan S, Fisher EA, Musunuru K, Rader DJ. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest. 2012 Aug 1;122(8):2807-16
- Khetarpal SA, Edmondson AC, Raghavan A, Neeli H, Jin W, Badellino KO, Demissie S, Manning AK, DerOhannessian SL, Wolfe ML, Cupples LA, Li M, Kathiresan S, Rader DJ. Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol. PLoS Genet. 2011 Dec;7(12):e1002393.
- Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, …, Kathiresan S, Samani NJ, Epstein SE, Rader DJ. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011 ;377(9763):383-92. PMID: 21239051
- Khera AV*, Cuchel M*, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky R, Mohler ER, Rothblat GH, Rader DJ. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med (2011) 364:12-20
- Burkhardt R*, Toh S*, Lagor WR, Birkeland A, Levin M, Li X, Robblee M, Fedorov VD, Yamamoto M, Satoh T, Akira S, Kathiresan S, Breslow JL* and Rader DJ*. Trib1, a novel lipid and myocardial infarction associated gene, regulates hepatic lipogenesis and VLDL production in mice. J Clin Invest (2010) 120(12):4410-4 PMID: 21084752
- Musunuru K*, Strong A*, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JJ, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S*, Rader DJ*. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature (2010) Aug 5;466(7307):714-9 PMID: 20686566
- Teslovich TM*, Musunuru K*, Smith AV, Edmondson AC, Stylianou IM, … Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Holm H, Reilly MP, Samani NJ, Schunkert H, Cupples LA*, Sandhu MS*, Ridker PM*, Rader DJ*, van Duijn CM*, Peltonen L*, Abecasis GR*, Boehnke M*, Kathiresan S*. Biological, Clinical, and Population Relevance of 95 Loci Mapped for Serum Lipid Concentrations. Nature (2010) Aug 5;466(7307):707-13 PMID: 20686565
- Cuchel M, Lund-Katz S, de la Llera-Moya M, Millar JS, Chang D, Fuki I, Rothblat GH, Phillips MC, Rader DJ. Pathways by which reconstituted high-density lipoprotein mobilizes free cholesterol from whole body and from macrophages. Arterioscler Thromb Vasc Biol 30(3):526-32 (2009) PMID: 20018934
- Griffon N, Jin W, Petty TJ, Millar J, Badellino KO, Saven JG, Marchadier DH, Kempner ES, Billheimer J, Glick JM, Rader DJ. Identification of the active form of endothelial lipase, a homodimer in a head-to-tail conformation. J Biol Chem 284(35):23322-30 (2009) PMID: 19567873
- Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, Jensen MK, Rimm EB, Wang J, Rodrigues A, Bamba V, Khetarpal SA, Wolfe ML, DerOhannessian S, Li M, Reilly MP, Aberle J, Evans D, Hegele RA, Rader DJ. Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J Clin Inves 119(4):1042-50 (2009) PMID: 19287092
- Badellino KO, Wolfe ML, Reilly MP, Rader DJ. Endothelial lipase is increased in vivo by inflammation in humans. Circulation 117:678-85 (2008) PMID: 18212282
- Tanigawa H, Billheimer JT, Tohyama J, Zhang Y, Rothblat G, Rader DJ. Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport. Circulation 116:1267-73 (2007) PMID: 17709636
- Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 117:2216-2224 (2007) PMID: 17657311
- Jin W, Wang X, Millar JS, Quertermous T, Rothblat GH, Glick JM, Rader DJ. Hepatic Proprotein Convertases Modulate HDL Metabolism. Cell Metab 6:129-136 (2007) PMID: 17681148
- Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in homozygous familial hypercholesterolemia. New Engl J Med 356:148-156 (2007) PMID: 17215532
Awards, Honors, Membership in Honorary Societies:
| • | Election to Institute of Medicine (2011) |
| • | Associate Editor, Journal of Clincial Investigation (2007) |
| • | International Atherosclerosis Society Distinguished Fellow (2007) |
| • | Election to Association of American Physicians (2007) |
| • | Bristol Myers Squibb “Freedom to Discover” Unrestricted Cardiovascular Research Grant (2005) |
| • | Cooper McClure Chair Professorship, University of Pennsylvania School of Medicine (2005) |
| • | William Osler Patient Oriented Research Award, University of Pennsylvania School of Medicine (2005) |
| • | Gill Heart Institute Award for Outstanding Contributions to Cardiovascular Research (2005) |
| • | Jeffrey M. Hoeg Award for Basic Science and Clinical Research, Arteriosclerosis, Thrombosis, and Vascular Biology Council of the American Heart Association (2005) |
| • | Doris Duke Charitable Foundation Distinguished Clinical Scientist Award (2002) |
| • | Listing in “Top Doctors of Philadelphia” Philadelphia Magazine (2002 – 2005) |
| • | Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (2000) |
| • | Established Investigator, American Heart Association (2000) |
| • | Election to American Society of Clinical Investigation (1999) |
| • | Donald B. Martin Outstanding Teacher Award (1997) |
| • | Outstanding Faculty Award, Department of Medicine (1996) |
| • | WW Smith Charitable Trust Awardee (1995) |
| • | Dean's Award, Medical College of Pennsylvania (1984) |
| • | Alpha Omega Alpha (1983) |
| • | Phi Beta Kappa (1979) |
Editorial Board Memberships:
| • | Editorial Board, Journal of Clinical Investigation (2007-present) |
| • | Editorial Board, Journal of Lipid Research (2005-present) |
| • | Editorial Board, Circulation Research (2002-present) |
| • | Editorial Board, Circulation (2002-present) |
| • | Editorial Board, American Journal of Physiology (Endocrinology and Metabolism) (2001-present) |
| • | Editorial Board, Arteriosclerosis, Thrombosis, and Vascular Biology (2000-present) |
| • | Editorial Board, Trends in Molecular Medicine (1999-present) |
Laboratory and Clinical Personnel:
| Name | Position | Telephone | Email Address |
| Bauer, Rob | Postdoctoral Fellow | 215-898-5909 | rcbauer@mail.med.upenn.edu |
| Billheimer, Jeff | Sr. Research Investigator | 215-746-0237 | billheij@mail.med.upenn.edu |
| Christopher, Devin | Graduate Student | 215-573-7666 | devc@mail.med.upenn.edu |
| Cromley, Debra | Research Specialist | 215-898-5909 | dcromley@mail.med.upenn.edu |
| Cuchel, Marina | Research Assistant Professor | 215-746-2834 | mcuchel@mail.med.upenn.edu |
| DerOhannessian, Stephanie | Project Manager | 215-746-6402 | srestine@mail.med.upenn.edu |
| Doveikis, Julia | Research Specialist | 215-746-6403 | doveikis@mail.med.upenn.edu |
| Edouard, Edwige | Research Specialist | 215-573-7666 | edwige2@mail.med.upenn.edu |
| Enriquez, Maria | Research Specialist | 215-746-4666 | mariaenriquez08@gmail.com |
| Khetarpal, Sumeet | MD/PhD Student | 215-746-6403 | sumeetak@mail.med.upenn.edu |
| Kim, Hyein | Rotating PhD Student | 215-746-6403 | Ihye@mail.med.upenn.edu |
| Kuwano, Takashi | Postdoctoral Fellow | 215-573-7666 | tkuwano@upenn.edu |
| Lagor, William | Research Associate | 215-573-5746 | wlagor@mail.med.upenn.edu |
| Lin, Wen | PhD Student | 215-573-7666 | linwen@mail.med.upenn.edu |
| Long, Shiyin | Visiting Scholar | 215-573-7666 | shiyinlo@upenn.edu |
| Lukmanova-Kegelman, Daniya | Research Specialist | 215-898-5909 | daniya@mail.med.upenn.edu |
| Marchadier, Dawn | Project Manager | 215-573-7534 | vista@mail.med.upenn.edu |
| May, Phyllis | Research Specialist | 215-746-6403 | plmay@mail.med.upenn.edu |
| McCoy, Mary | Research Assistant | 215-898-5909 | mmccoy@neumann.edu |
| Mehta, Minal | PhD Student | 215-746-6403 | mimehta@mail.med.upenn.edu |
| Millar, John | Sr. Research Investigator | 215-898-0638 | jsmillar@mail.med.upenn.edu |
| Morrell, Linda | Research Specialist | 215-573-4121 | lmorrell@mail.med.upenn.edu |
| Mucksavage, Megan | Project Manager | 215-746-0358 | mewolfe@mail.med.upenn.edu |
| Pashos, Evanthia | Postdoctoral Fellow | 215-898-5909 | evpashos@mail.med.upenn.edu |
| Patel, Kevin | PhD Student | 215-573-7666 | kevinmpatel@gmail.com |
| Picataggi, Antonino | Research Specialist | 215-898-5909 | apicci@gmail.com |
| Qu, Liming | Biostatistician | 215-746-3886 | qui@mail.med.upenn.edu |
| Rader, Dan | Principal Investigator | 215-573-4176 | rader@mail.med.upenn.edu |
| Redon, Valeska | Research Specialist | 215-898-6955 | valeska@mail.med.upenn.edu |
| Rodrigues, Amrith | Research Specialist | 215-898-5909 | amrith@mail.med.upenn.edu |
| Saleheen, Danish | Research Associate | 215-573-6323 | saleheen@mail.med.upenn.edu |
| Strong, Alanna | MD/PhD Student | 215-746-6403 | astrong@mail.med.upenn.edu |
| Sun, Maosen | Research Specialist | 215-573-7666 | maosen@mail.med.upenn.edu |
| Tohyama, Junichiro | Postdoctoral Fellow | 215-746-6403 | junichi2@mail.med.upenn.edu |
| Trindade, Kevin | Research Specialist | 215-746-6403 | kevintri@mail.med.upenn.edu |
| Tuteja, Sony | Postdoctoral Fellow | 215-573-7834 | sony.tuteja@gmail.com |
| Wilson, Aisha | Research Specialist | 215-573-7666 | faruqi@mail.med.upenn.edu |
| Zanoni, Paolo | Postdoctoral Fellow | 215-573-7666 | paolo.zanoni2@studio.unibo.it |
| Zhaow, Wei | Jr. Biostatistician | 215-898-9332 | zhaowei1@mail.med.upenn.edu> |
| Administration | |||
| Carmichael, Linda | Administrative Assistant | 215-573-4176 | lincarm@upenn.edu |
| Nagelberg, Jonathan | Business Administrator / Grants Manager | 215-573-1264 | jnage@upenn.edu |
| Warford, Cathy | Executive Assistant | 215-743-7272 | cwarford@mail.med.upenn.edu |
| Lab Fax | 215-573-8606 | ||
Research Lab Address:
11th Floor Smilow Center for Translational ResearchUniversity of Pennsylvania
3400 Civic Center Blvd, Bldg 421
Philadelphia, PA 19104-5158
Clinical Research Lab Address:
East Pavilion, 2nd FloorPerelman Center for Advanced Medicine
University of Pennsylvania
3400 Civic Center Blvd
Philadelphia, PA 19104