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

Selected Publications

Rader DJ.: Apolipoprotein A-I Infusion Therapies for Coronary Disease: Two Outs in the Ninth Inning and Swinging for the Fences JAMA Cardiol 3 (9): 799-801,2018.

Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, Baum SJ, Bourbon M, Carrié A, Cuchel M, de Ferranti SD, Defesche JC, Freiberger T, Hershberger RE, Hovingh GK, Karayan L, Kastelein JJP, Kindt I, Lane SR, Leigh SE, Linton MF, Mata P, Neal WA, Nordestgaard BG, Santos RD, Harada-Shiba M, Sijbrands EJ, Stitziel NO, Yamashita S, Wilemon KA, Ledbetter DH, Rader DJ; Convened by the Familial Hypercholesterolemia Foundation.: Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel J Am Coll Cardiol 72 (6): 662-680,2018.

Pirro M, Ricciuti B, Rader DJ, Catapano AL, Sahebkar A, Banach M.: High density lipoprotein cholesterol and cancer: Marker or causative? Prog Lipid Res 71 : 54-69,2018.

Khetarpal SA, Babb PL, Zhao W, Hancock-Cerutti WF, Brown CD, Rader DJ, Voight BF.: Multiplexed Targeted Resequencing Identifies Coding and Regulatory Variation Underlying Phenotypic Extremes of High-Density Lipoprotein Cholesterol in Humans Circ Genom Precis Med 11 (7): e002070,2018.

Toth PP, Dwyer JP, Cannon CP, Colhoun HM, Rader DJ, Upadhyay A, Louie MJ, Koren A, Letierce A, Mandel J, Banach M.: Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease Kidney Int 93 (6): 1397-1408,2018.

Daugherty A, Lu HS, Hegele RA, Mackman N, Rader DJ, Schmidt AM, Weber C.: Response by Daugherty et al to Letter Regarding Article, "Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the Arteriosclerosis, Thrombosis, and Vascular Biology Council" Arterioscler Thromb Vasc Biol 38 (6): e101-e102,2018.

Mehta NN, Shin DB, Joshi AA, Dey AK, Armstrong AW, Duffin KC, Fuxench ZC, Harrington CL, Hubbard RA, Kalb RE, Menter A, Rader DJ, Reilly MP, Simpson EL, Takeshita J, Torigian DA, Werner TJ, Troxel AB, Tyring SK, Vanderbeek SB, Van Voorhees AS, Playford MP, Ahlman MA, Alavi A, Gelfand JM.: Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial Circ Cardiovasc Imaging 11 (6): e007394,2018.

Gusarova V, O'Dushlaine C, Teslovich TM, Benotti PN, Mirshahi T, Gottesman O, Van Hout CV, Murray MF, Mahajan A, Nielsen JB, Fritsche L, Wulff AB, Gudbjartsson DF, Sjögren M, Emdin CA, Scott RA, Lee WJ, Small A, Kwee LC, Dwivedi OP, Prasad RB, Bruse S, Lopez AE, Penn J, Marcketta A, Leader JB, Still CD, Kirchner HL, Mirshahi UL, Wardeh AH, Hartle CM, Habegger L, Fetterolf SN, Tusie-Luna T, Morris AP, Holm H, Steinthorsdottir V, Sulem P, Thorsteinsdottir U, Rotter JI, Chuang LM, Damrauer S, Birtwell D, Brummett CM, Khera AV, Natarajan P, Orho-Melander M, Flannick J, Lotta LA, Willer CJ, Holmen OL, Ritchie MD, Ledbetter DH, Murphy AJ, Borecki IB, Reid JG, Overton JD, Hansson O, Groop L, Shah SH, Kraus WE, Rader DJ, Chen YI, Hveem K, Wareham NJ, Kathiresan S, Melander O, Stefansson K, Nordestgaard BG, Tybjærg-Hansen A, Abecasis GR, Altshuler D, Florez JC, Boehnke M, McCarthy MI, Yancopoulos GD, Carey DJ, Shuldiner AR, Baras A, Dewey FE, Gromada J.: Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes Nat Commun 9 (1): 2252,2018.

Roselli C, Chaffin MD, Weng LC, Aeschbacher S, Ahlberg G, Albert CM, Almgren P, Alonso A, Anderson CD, Aragam KG, Arking DE, Barnard J, Bartz TM, Benjamin EJ, Bihlmeyer NA, Bis JC, Bloom HL, Boerwinkle E, Bottinger EB, Brody JA, Calkins H, Campbell A, Cappola TP, Carlquist J, Chasman DI, Chen LY, Chen YI, Choi EK, Choi SH, Christophersen IE, Chung MK, Cole JW, Conen D, Cook J, Crijns HJ, Cutler MJ, Damrauer SM, Daniels BR, Darbar D, Delgado G, Denny JC, Dichgans M, Dörr M, Dudink EA, Dudley SC, Esa N, Esko T, Eskola M, Fatkin D, Felix SB, Ford I, Franco OH, Geelhoed B, Grewal RP, Gudnason V, Guo X, Gupta N, Gustafsson S, Gutmann R, Hamsten A, Harris TB, Hayward C, Heckbert SR, Hernesniemi J, Hocking LJ, Hofman A, Horimoto ARVR, Huang J, Huang PL, Huffman J, Ingelsson E, Ipek EG, Ito K, Jimenez-Conde J, Johnson R, Jukema JW, Kääb S, Kähönen M, Kamatani Y, Kane JP, Kastrati A, Kathiresan S, Katschnig-Winter P, Kavousi M, Kessler T, Kietselaer BL, Kirchhof P, Kleber ME, Knight S, Krieger JE, Kubo M, Launer LJ, Laurikka J, Lehtimäki T, Leineweber K, Lemaitre RN, Li M, Lim HE, Lin HJ, Lin H, et al.: Multi-ethnic genome-wide association study for atrial fibrillation Nat Genet 50 (9): 1225-1233,2018.

Olshan DS, Rader DJ.: Angiopoietin-like protein 4: A therapeutic target for triglycerides and coronary disease? J Clin Lipidol 12 (3): 583-587,2018.

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Academic Contact Information

Perelman School of Medicine
University of Pennsylvania
11-125 Smilow Center for Translational Research
3400 Civic Center Blvd

Philadelphia, PA 19104-5158
Phone: 215-573-4176
Patient appointments: 800-789-7366