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Civelek, Mete

Mete Civelek

Primary Appointment

Biomedical Engineering

Contact Information

OMS, Room 3836A
Charlottesville, VA 22908
Telephone: 434-243-1669
Fax: 434-924-1312
Email: mc2wq@virginia.edu

Research Interests

Systems Genetics Approaches to Understand Cardiometabolic Traits

Research Description

The goal of our laboratory is to understand the genetic mechanisms that lead to increased susceptibility to cardiovascular and metabolic diseases. The interactions among hundreds of genes and gene networks along with environmental factors such as diet affect our health status. We use systems genetics to uncover this complexity. We use a range of experimental and computational methods to quantitate and integrate intermediate phenotypes, such as transcript, protein or metabolite levels, in human and mouse populations. We also test our predictions using standard biochemistry and molecular biology approaches in cell cultures and animal models. Our results provided insights into both the molecular underpinnings of complex traits and the understanding of common, complex diseases.

Selected Publications

Bennett BJ, Davis RC, Civelek M, Orozco L, Wu J, Qi H, Pan C, Sevag Packard RR, Eskin E, Yan M, Kirchgessner T, Wang Z, Li X, Gregory JC, Hazen SL, Gargalovic PS, Lusis AJ, Correction: Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains., 2016; PLoS genetics. 12(3) e1005913 PMID: 26934746 | PMCID: PMC4775237

Talukdar HA, Foroughi Asl H, Jain RK, Ermel R, Ruusalepp A, Franz?n O, Kidd BA, Readhead B, Giannarelli C, Kovacic JC, Ivert T, Dudley JT, Civelek M, Lusis AJ, Schadt EE, Skogsberg J, Michoel T, Bj?rkegren JL, Cross-Tissue Regulatory Gene Networks in Coronary Artery Disease., 2016; Cell systems. 2(3) 196-208 PMID: 27135365 | PMCID: PMC4855300

Lusis AJ, Seldin MM, Allayee H, Bennett BJ, Civelek M, Davis RC, Eskin E, Farber CR, Hui S, Mehrabian M, Norheim F, Pan C, Parks B, Rau CD, Smith DJ, Vallim T, Wang Y, Wang J, The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits., 2016; Journal of lipid research. 57(6) 925-42 PMID: 27099397 | PMCID: PMC4878195

Bennett BJ, Davis RC, Civelek M, Orozco L, Wu J, Qi H, Pan C, Packard RR, Eskin E, Yan M, Kirchgessner T, Wang Z, Li X, Gregory JC, Hazen SL, Gargalovic PS, Lusis AJ, Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains., 2015; PLoS genetics. 11(12) e1005711 PMID: 26694027 | PMCID: PMC4687930

Briot A, Civelek M, Seki A, Hoi K, Mack JJ, Lee SD, Kim J, Hong C, Yu J, Fishbein GA, Vakili L, Fogelman AM, Fishbein MC, Lusis AJ, Tontonoz P, Navab M, Berliner JA, Iruela-Arispe ML, Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis., 2015; The Journal of experimental medicine. 212(12) 2147-63 PMID: 26552708 | PMCID: PMC4647265

Br?nne I, Civelek M, Vilne B, Di Narzo A, Johnson AD, Zhao Y, Reiz B, Codoni V, Webb TR, Foroughi Asl H, Hamby SE, Zeng L, Tr?gou?t DA, Hao K, Topol EJ, Schadt EE, Yang X, Samani NJ, Bj?rkegren JL, Erdmann J, Schunkert H, Lusis AJ, Prediction of Causal Candidate Genes in Coronary Artery Disease Loci., 2015; Arteriosclerosis, thrombosis, and vascular biology. 35(10) 2207-17 PMID: 26293461 | PMCID: PMC4583353

Soccio RE, Chen ER, Rajapurkar SR, Safabakhsh P, Marinis JM, Dispirito JR, Emmett MJ, Briggs ER, Fang B, Everett LJ, Lim HW, Won KJ, Steger DJ, Wu Y, Civelek M, Voight BF, Lazar MA, Genetic Variation Determines PPAR? Function and Anti-diabetic Drug Response In Vivo., 2015; Cell. 162(1) 33-44 PMID: 26140591 | PMCID: PMC4493773

Wu C, Huang RT, Kuo CH, Kumar S, Kim CW, Lin YC, Chen YJ, Birukova A, Birukov KG, Dulin NO, Civelek M, Lusis AJ, Loyer X, Tedgui A, Dai G, Jo H, Fang Y, Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces., 2015; Circulation research. 117(4) e41-53 PMID: 26034042 | PMCID: PMC4522239

Kenagy RD, Civelek M, Kikuchi S, Chen L, Grieff A, Sobel M, Lusis AJ, Clowes AW, Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency., 2015; Journal of vascular surgery. 64(1) 202-209.e6 PMID: 25935274 | PMCID: PMC4627903

Bahn JH, Ahn J, Lin X, Zhang Q, Lee JH, Civelek M, Xiao X, Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways., 2015; Nature communications. 6() 6355 PMID: 25751603 | PMCID: PMC4355961

Romay MC, Che N, Becker SN, Pouldar D, Hagopian R, Xiao X, Lusis AJ, Berliner JA, Civelek M, Regulation of NF-?B signaling by oxidized glycerophospholipid and IL-1? induced miRs-21-3p and -27a-5p in human aortic endothelial cells., 2014; Journal of lipid research. 56(1) 38-50 PMID: 25327529 | PMCID: PMC4274069

Germain M, Pezzolesi MG, Sandholm N, McKnight AJ, Susztak K, Lajer M, Forsblom C, Marre M, Parving HH, Rossing P, Toppila I, Skupien J, Roussel R, Ko YA, Ledo N, Folkersen L, Civelek M, Maxwell AP, Tregouet DA, Groop PH, Tarnow L, Hadjadj S, SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes., 2014; Diabetologia. 58(3) 543-8 PMID: 25476525 |

Civelek M, Lusis AJ, From hairballs to an understanding of transendothelial migration of monocytes in atherosclerosis., 2014; Arteriosclerosis, thrombosis, and vascular biology. 34(9) 1809-10 PMID: 25142882 | PMCID: PMC4142522

Iatan I, Choi HY, Ruel I, Reddy MV, Kil H, Lee J, Odeh MA, Salah Z, Abu-Remaileh M, Weissglas-Volkov D, Nikkola E, Civelek M, Awan Z, Croce CM, Aqeilan RI, Pajukanta P, Aldaz CM, Genest J, The WWOX gene modulates high-density lipoprotein and lipid metabolism., 2014; Circulation. Cardiovascular genetics. 7(4) 491-504 PMID: 24871327 | PMCID: PMC4315188

Civelek M, Lusis AJ, Systems genetics approaches to understand complex traits., 2013; Nature reviews. Genetics. 15(1) 34-48 PMID: 24296534 | PMCID: PMC3934510

Parks BW, Nam E, Org E, Kostem E, Norheim F, Hui ST, Pan C, Civelek M, Rau CD, Bennett BJ, Mehrabian M, Ursell LK, He A, Castellani LW, Zinker B, Kirby M, Drake TA, Drevon CA, Knight R, Gargalovic P, Kirchgessner T, Eskin E, Lusis AJ, Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice., 2013; Cell metabolism. 17(1) 141-52 PMID: 23312289 | PMCID: PMC3545283

de Aguiar Vallim TQ, Tarling EJ, Kim T, Civelek M, Bald?n ?, Esau C, Edwards PA, MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor., 2013; Circulation research. 112(12) 1602-12 PMID: 23519696 | PMCID: PMC3995747

Erbilgin A, Civelek M, Romanoski CE, Pan C, Hagopian R, Berliner JA, Lusis AJ, Identification of CAD candidate genes in GWAS loci and their expression in vascular cells., 2013; Journal of lipid research. 54(7) 1894-905 PMID: 23667179 | PMCID: PMC3679391

Davies PF, Civelek M, Fang Y, Fleming I, The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo., 2013; Cardiovascular research. 99(2) 315-27 PMID: 23619421 | PMCID: PMC3695748

Civelek M, Hagopian R, Pan C, Che N, Yang WP, Kayne PS, Saleem NK, Cederberg H, Kuusisto J, Gargalovic PS, Kirchgessner TG, Laakso M, Lusis AJ, Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits., 2013; Human molecular genetics. 22(15) 3023-37 PMID: 23562819 | PMCID: PMC3699064

Mahendran Y, Vangipurapu J, Cederberg H, Stanc?kov? A, Pihlajam?ki J, Soininen P, Kangas AJ, Paananen J, Civelek M, Saleem NK, Pajukanta P, Lusis AJ, Bonnycastle LL, Morken MA, Collins FS, Mohlke KL, Boehnke M, Ala-Korpela M, Kuusisto J, Laakso M, Association of ketone body levels with hyperglycemia and type 2 diabetes in 9,398 Finnish men., 2013; Diabetes. 62(10) 3618-26 PMID: 23557707 | PMCID: PMC3781437

Kim JB, Deluna A, Mungrue IN, Vu C, Pouldar D, Civelek M, Orozco L, Wu J, Wang X, Charugundla S, Castellani LW, Rusek M, Jakubowski H, Jakobowski H, Lusis AJ, Effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice., 2012; Circulation. 126(15) 1896-906 PMID: 22952318 | PMCID: PMC3608429

Stanc?kov? A, Civelek M, Saleem NK, Soininen P, Kangas AJ, Cederberg H, Paananen J, Pihlajam?ki J, Bonnycastle LL, Morken MA, Boehnke M, Pajukanta P, Lusis AJ, Collins FS, Kuusisto J, Ala-Korpela M, Laakso M, Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men., 2012; Diabetes. 61(7) 1895-902 PMID: 22553379 | PMCID: PMC3379649

Haas BE, Horvath S, Pietil?inen KH, Cantor RM, Nikkola E, Weissglas-Volkov D, Rissanen A, Civelek M, Cruz-Bautista I, Riba L, Kuusisto J, Kaprio J, Tusie-Luna T, Laakso M, Aguilar-Salinas CA, Pajukanta P, Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes., 2012; BMC medical genomics. 5() 61 PMID: 23217153 | PMCID: PMC3543280

Romanoski CE, Che N, Yin F, Mai N, Pouldar D, Civelek M, Pan C, Lee S, Vakili L, Yang WP, Kayne P, Mungrue IN, Araujo JA, Berliner JA, Lusis AJ, Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1., 2011; Circulation research. 109(5) e27-41 PMID: 21737788 | PMCID: PMC3163234

Civelek M, Lusis AJ, Conducting the metabolic syndrome orchestra., 2011; Nature genetics. 43(6) 506-8 PMID: 21614088 | PMCID: PMC3934506

Civelek M, Manduchi E, Grant GR, Stoeckert CJ, Davies PF, Discovery approaches to UPR in athero-susceptible endothelium in vivo., 2011; Methods in enzymology. 489() 109-26 PMID: 21266227 | PMCID: PMC3833809

Civelek M, Manduchi E, Riley RJ, Stoeckert CJ, Davies PF, Coronary artery endothelial transcriptome in vivo: identification of endoplasmic reticulum stress and enhanced reactive oxygen species by gene connectivity network analysis., 2011; Circulation. Cardiovascular genetics. 4(3) 243-52 PMID: 21493819 | PMCID: PMC3116084

Davies PF, Civelek M, Endoplasmic reticulum stress, redox, and a proinflammatory environment in athero-susceptible endothelium in vivo at sites of complex hemodynamic shear stress., 2010; Antioxidants & redox signaling. 15(5) 1427-32 PMID: 21126204 | PMCID: PMC3144426

Davies PF, Civelek M, Fang Y, Guerraty MA, Passerini AG, Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo., 2010; Seminars in thrombosis and hemostasis. 36(3) 265-75 PMID: 20533180 | PMCID: PMC3817717

Fang Y, Shi C, Manduchi E, Civelek M, Davies PF, MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro., 2010; Proceedings of the National Academy of Sciences of the United States of America. 107(30) 13450-5 PMID: 20624982 | PMCID: PMC2922125

Civelek M, Grant GR, Irolla CR, Shi C, Riley RJ, Chiesa OA, Stoeckert CJ, Karanian JW, Pritchard WF, Davies PF, Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo., 2009; American journal of physiology. Heart and circulatory physiology. 298(1) H163-70 PMID: 19897713 | PMCID: PMC2806137

Civelek M, Manduchi E, Riley RJ, Stoeckert CJ, Davies PF, Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis., 2009; Circulation research. 105(5) 453-61 PMID: 19661457 | PMCID: PMC2746924

Civelek M, Ainslie K, Garanich JS, Tarbell JM, Smooth muscle cells contract in response to fluid flow via a Ca2+-independent signaling mechanism., 2002; Journal of applied physiology (Bethesda, Md. : 1985). 93(6) 1907-17 PMID: 12391063 |

Sharma R, Yellowley CE, Civelek M, Ainslie K, Hodgson L, Tarbell JM, Donahue HJ, Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow., 2002; Annals of biomedical engineering. 30(3) 371-8 PMID: 12051621 | PMCID: PMC4472337