Description of Research Expertise:
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
11th floor, Smilow Center for Translational Research
9th floor Maloney Building, Hospital of The University of Pennsylvania
Small AM, Mehta NN, Rader DJ: The Role of Emerging Biomarkers in Unraveling the Complex Biology Underlying Associations between HDL Cholesterol and Cardiovascular Diseases. Clin Chem 63 (1): 27-29,2017.
Rader DJ, Damrauer SM: "Pheno"menal value for human health. Science 354 (6319): 1534-1536,2016.
Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O, Orho-Melander M, Ridker PM, Kathiresan S.: Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med 375 (24): 2349-2358,2016.
Emdin CA, Khera AV, Natarajan P, Klarin D, Baber U, Mehran R, Rader DJ, Fuster V, Kathiresan S.: Evaluation of the Pooled Cohort Equations for Prediction of Cardiovascular Risk in a Contemporary Prospective Cohort. Am J Cardiol : 2016.
Emdin CA, Khera AV, Natarajan P, Klarin D, Won HH, Peloso GM, Stitziel NO, Nomura A, Zekavat SM, Bick AG, Gupta N, Asselta R, Duga S, Merlini PA, Correa A, Kessler T, Wilson JG, Bown MJ, Hall AS, Braund PS, Samani NJ, Schunkert H, Marrugat J, Elosua R, McPherson R, Farrall M, Watkins H, Willer C, Abecasis GR, Felix JF, Vasan RS, Lander E, Rader DJ, Danesh J, Ardissino D, Gabriel S, Saleheen D, Kathiresan S; CHARGE–Heart Failure Consortium.; CARDIoGRAM Exome Consortium.: Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels. J Am Coll Cardiol 68 (25): 2761-2772,2016.
Natarajan P, Bis JC, Bielak LF, Cox AJ, Dörr M, Feitosa MF, Franceschini N, Guo X, Hwang SJ, Isaacs A, Jhun MA, Kavousi M, Li-Gao R, Lyytikäinen LP, Marioni RE, Schminke U, Stitziel NO, Tada H, van Setten J, Smith AV, Vojinovic D, Yanek LR, Yao J, Yerges-Armstrong LM, Amin N, Baber U, Borecki IB, Carr JJ, Chen YI, Cupples LA, de Jong PA, de Koning H, de Vos BD, Demirkan A, Fuster V, Franco OH, Goodarzi MO, Harris TB, Heckbert SR, Heiss G, Hoffmann U, Hofman A, Išgum I, Jukema JW, Kähönen M, Kardia SL, Kral : Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis. Circ Cardiovasc Genet 9 (6): 511-520,2016.
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 35 (11): 1295-1302,2016.
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 152 (11): 1244-1253,2016.
Roth EM, Moriarty PM, Bergeron J, Langslet G, Manvelian G, Zhao J, Baccara-Dinet MT, Rader DJ; ODYSSEY CHOICE I investigators: A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis 254 : 254-262,2016.
Joshi AA, Lerman JB, Aberra TM, Afshar M, Teague HL, Rodante JA, Krishnamoorthy P, Ng Q, Aridi TZ, Salahuddin T, Natarajan B, Lockshin BN, Ahlman MA, Chen MY, Rader DJ, Reilly M, Remaley AT, Bluemke DA, Playford MP, Gelfand JM, Mehta NN: GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis. Circ Res 119 (11): 1242-1253,2016.
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