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
8th floor Maloney Building, Hospital of The University of Pennsylvania
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 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.
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 Apr 2015 Notes: [Epub ahead of print]
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 Apr 2015 Notes: Epub ahead of print
Stitziel NO, Peloso GM, Abifadel M, Cefalu AB, Fouchier S, Motazacker MM, Tada H, Larach DB, Awan Z, Haller JF, Pullinger CR, Varret M, Rabès JP, Noto D, Tarugi P, Kawashiri MA, Nohara A, Yamagishi M, Risman M, Deo R, Ruel I, Shendure J, Nickerson DA, Wilson JG, Rich SS, Gupta N, Farlow DN, Neale BM, Daly MJ, Kane JP, Freeman MW, Genest J, Rader DJ, Mabuchi H, Kastelein JJ, Hovingh GK, Averna MR, Gabriel S, Boileau C, Kathiresan S: Exome sequencing in suspected monogenic dyslipidemias. Circ Cardiovasc Genet 8(2): 343-350, Apr 2015.
Nelson CP, Hamby SE, Saleheen D, Hopewell JC, Zeng L, Assimes TL, Kanoni S, Willenborg C, Burgess S, Amouyel P, Anand S, Blankenberg S, Boehm BO, Clarke RJ, Collins R, Dedoussis G, Farrall M, Franks PW, Groop L, Hall AS, Hamsten A, Hengstenberg C, Hovingh GK, Ingelsson E, Kathiresan S, Kee F, König IR, Kooner J, Lehtimäki T, März W, McPherson R, Metspalu A, Nieminen MS, O'Donnell CJ, Palmer CN, Peters A, Perola M, Reilly MP, Ripatti S, Roberts R, Salomaa V, Shah SH, Schreiber S, Siegbahn A, Thorsteinsdottir U, Veronesi G, Wareham N, Willer CJ, Zalloua PA, Erdmann J, Deloukas P, Watkins H, Schunkert H, Danesh J, Thompson JR, Samani NJ; CARDIoGRAM+C4D Consortium. : Genetically determined height and coronary artery disease. N Engl J Med. 372(17): 1608-1618, Apr 2015.
Kaess BM, Preis SR, Lieb W, Beiser AS, Yang Q, Chen TC, Hengstenberg C, Erdmann J, Schunkert H, Seshadri S, Vasan RS; CARDIoGRAM, Assimes TL, Deloukas P, Holm H, Kathiresan S, König IR, McPherson R, Reilly MP, Roberts R, Samani NJ, Stewart AF: Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community. J Am Heart Assoc 4(3): e001544, Mar 2015.
Bauer RC, Tohyama J, Cui J, Cheng L, Yang J, Zhang X, Ou K, Paschos GK, Zheng XL, Parmacek MS, Rader DJ, Reilly MP: Knockout of adamts7, a novel coronary artery disease locus in humans, reduces atherosclerosis in mice. Circulation 131(13): 1202-1213, Mar 2015.
Shah R, Matthews GJ, Shah RY, McLaughlin C, Chen J, Wolman M, Master SR, Chai B, Xie D, Rader DJ, Raj DS, Mehta NN, Budoff M, Fischer MJ, Go AS, Townsend RR, He J, Kusek JW, Feldman HI, Foulkes AS, Reilly MP; CRIC Study Investigators: Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis Mar 2015 Notes: [Epub ahead of print]
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Last updated: 05/12/2015
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