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
Vitali C, Rader DJ, Cuchel M.: Novel therapeutic opportunities for familial lecithin:cholesterol acyltransferase deficiency: promises and challenges. Curr Opin Lipidol 34: 35-43, Apr 2023.
Small AM, Peloso GM, Linefsky J, Aragam J, Galloway A, Tanukonda V, Wang LC, Yu Z, Sunitha Selvaraj M, Farber-Eger EH, Baker MT, Setia-Verma S, Lee SSK, Preuss M, Ritchie MD, Damrauer SM, Rader DJ, Wells QS, Loos R, Lubitz SA, Thanassoulis G, Cho K, Wilson PWF; VA Million Veteran Program; Natarajan P, O'Donnell CJ.: Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program. Circulation 147: 942-955, Mar 2023.
Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, Moriarty PM, Rubba P, Whitcomb DC, Banerjee P, Gewitz A, Gonzaga-Jauregui C, McGinniss J, Ponda MP, Pordy R, Zhao J, Rader DJ.: Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nat Med 29(3): 729-737, Mar 2023.
Hui D, Mehrabi S, Quimby AE, Chen T, Chen S, Park J, Li B; Regeneron Genetics Center; Penn Medicine Biobank; Ruckenstein MJ, Rader DJ, Ritchie MD, Brant JA, Epstein DJ, Mathieson I.: Gene burden analysis identifies genes associated with increased risk and severity of adult-onset hearing loss in a diverse hospital-based cohort. PLoS Genet 19: e1010584, Jan 2023.
Krychtiuk KA, Rader DJ, Granger CB.: RNA-targeted therapeutics in cardiovascular disease: the time is now. Eur Heart J Cardiovasc Pharmacother 9: 94-99, Dec 2022.
Huang J, Huffman JE, Huang Y, Do Valle Í, Assimes TL, Raghavan S, Voight BF, Liu C, Barabási AL, Huang RDL, Hui Q, Nguyen XT, Ho YL, Djousse L, Lynch JA, Vujkovic M, Tcheandjieu C, Tang H, Damrauer SM, Reaven PD, Miller D, Phillips LS, Ng MCY, Graff M, Haiman CA, Loos RJF, North KE, Yengo L, Smith GD, Saleheen D, Gaziano JM, Rader DJ, Tsao PS, Cho K, Chang KM, Wilson PWF; VA Million Veteran Program; Sun YV, O'Donnell CJ.: Genomics and phenomics of body mass index reveals a complex disease network. Nat Commun 13: 7973, Dec 2022.
Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, et al.: Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. Genome Biol 23: 268, Dec 2022.
Ko YA, Billheimer JT, Lyssenko NN, Kueider-Paisley A, Wolk DA, Arnold SE, Leung YY, Shaw LM, Trojanowski JQ, Kaddurah-Daouk RF, Kling MA, Rader DJ.: ApoJ/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer's disease. Alzheimers Res Ther 14: 194, Dec 2022.
Park J, MacLean MT, Lucas AM, Torigian DA, Schneider CV, Cherlin T, Xiao B, Miller JE, Bradford Y, Judy RL; Regeneron Genetics Center; Verma A, Damrauer SM, Ritchie MD, Witschey WR, Rader DJ.: Exome-wide association analysis of CT imaging-derived hepatic fat in a medical biobank. Cell Rep Med 3: 100855, Dec 2022.
Taylor SC, Gehringer BN, Dow HC, Langer A, Rawot E, Smernoff Z, Steeman S, Almasy L, Rader DJ, Bučan M, Brodkin ES.: Contrasting Views of Autism Spectrum Traits in Adults, Especially in Self-Reports vs. Informant-Reports for Women High in Autism Spectrum Traits. J Autism Dev Disord Dec 2022.
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Last updated: 04/10/2023
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