Mete Civelek

Education

  • BS, Bogazici University
  • BA, Bogazici University
  • MS, Pennsylvania State University, University Park, PA
  • PhD, University of Pennsylvania

Primary Appointment

  • Assistant Professor, Biomedical Engineering

Contact

Research Interest(s)

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 B, Davis R, Civelek M, Orozco L, Wu J, Qi H, Pan C, Sevag Packard R, Eskin E, Yan M, Kirchgessner T, Wang Z, Li X, Gregory J, Hazen S, Gargalovic P, Lusis A. Correction: Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS genetics. 2016;12(3): e1005913. PMID: 26934746 | PMCID: PMC4775237
  • Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx B, Jansen R, de Geus E, Boomsma D, Wright F, Sullivan P, Nikkola E, Alvarez M, Civelek M, Lusis A, Lehtimäki T, Raitoharju E, Kähönen M, Seppälä I, Raitakari O, Kuusisto J, Laakso M, Price A, Pajukanta P, Pasaniuc B. Integrative approaches for large-scale transcriptome-wide association studies. Nature genetics. 2016;48(3): 245-52. PMID: 26854917 | PMCID: PMC4767558
  • Kojima Y, Volkmer J, McKenna K, Civelek M, Lusis A, Miller C, Direnzo D, Nanda V, Ye J, Connolly A, Schadt E, Quertermous T, Betancur P, Maegdefessel L, Matic L, Hedin U, Weissman I, Leeper N. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016. PMID: 27437576 | PMCID: PMC4980260
  • Lusis A, Seldin M, Allayee H, Bennett B, Civelek M, Davis R, Eskin E, Farber C, Hui S, Mehrabian M, Norheim F, Pan C, Parks B, Rau C, Smith D, Vallim T, Wang Y, Wang J. The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits. Journal of lipid research. 2016;57(6): 925-42. PMID: 27099397 | PMCID: PMC4878195
  • Talukdar H, Foroughi Asl H, Jain R, Ermel R, Ruusalepp A, Franzén O, Kidd B, Readhead B, Giannarelli C, Kovacic J, Ivert T, Dudley J, Civelek M, Lusis A, Schadt E, Skogsberg J, Michoel T, Björkegren J. Cross-Tissue Regulatory Gene Networks in Coronary Artery Disease. Cell systems. 2016;2(3): 196-208. PMID: 27135365 | PMCID: PMC4855300
  • Bahn J, Ahn J, Lin X, Zhang Q, Lee J, Civelek M, Xiao X. Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways. Nature communications. 2015;6 6355. PMID: 25751603 | PMCID: PMC4355961
  • Bennett B, Davis R, Civelek M, Orozco L, Wu J, Qi H, Pan C, Packard R, Eskin E, Yan M, Kirchgessner T, Wang Z, Li X, Gregory J, Hazen S, Gargalovic P, Lusis A. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS genetics. 2015;11(12): e1005711. PMID: 26694027 | PMCID: PMC4687930
  • Briot A, Civelek M, Seki A, Hoi K, Mack J, Lee S, Kim J, Hong C, Yu J, Fishbein G, Vakili L, Fogelman A, Fishbein M, Lusis A, Tontonoz P, Navab M, Berliner J, Iruela-Arispe M. Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis. The Journal of experimental medicine. 2015;212(12): 2147-63. PMID: 26552708 | PMCID: PMC4647265
  • Brænne I, Civelek M, Vilne B, Di Narzo A, Johnson A, Zhao Y, Reiz B, Codoni V, Webb T, Foroughi Asl H, Hamby S, Zeng L, Trégouët D, Hao K, Topol E, Schadt E, Yang X, Samani N, Björkegren J, Erdmann J, Schunkert H, Lusis A. Prediction of Causal Candidate Genes in Coronary Artery Disease Loci. Arteriosclerosis, thrombosis, and vascular biology. 2015;35(10): 2207-17. PMID: 26293461 | PMCID: PMC4583353
  • Germain M, Chasman D, de Haan H, Tang W, Lindström S, Weng L, de Andrade M, de Visser M, Wiggins K, Suchon P, Saut N, Smadja D, Le Gal G, van Hylckama Vlieg A, Di Narzo A, Hao K, Nelson C, Rocanin-Arjo A, Folkersen L, Monajemi R, Rose L, Brody J, Slagboom E, Aïssi D, Gagnon F, Deleuze J, Deloukas P, Tzourio C, Dartigues J, Berr C, Taylor K, Civelek M, Eriksson P, Psaty B, Houwing-Duitermaat J, Goodall A, Cambien F, Kraft P, Amouyel P, Samani N, Basu S, Ridker P, Rosendaal F, Kabrhel C, Folsom A, Heit J, Reitsma P, Trégouët D, Smith N, Morange P. Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. American journal of human genetics. 2015;96(4): 532-42. PMID: 25772935 | PMCID: PMC4385184
  • Kenagy R, Civelek M, Kikuchi S, Chen L, Grieff A, Sobel M, Lusis A, Clowes A. Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency. Journal of vascular surgery. 2015;64(1): 202-209.e6. PMID: 25935274 | PMCID: PMC4627903
  • Roman T, Marvelle A, Fogarty M, Vadlamudi S, Gonzalez A, Buchkovich M, Huyghe J, Fuchsberger C, Jackson A, Wu Y, Civelek M, Lusis A, Gaulton K, Sethupathy P, Kangas A, Soininen P, Ala-Korpela M, Kuusisto J, Collins F, Laakso M, Boehnke M, Mohlke K. Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol. American journal of human genetics. 2015;97(6): 801-15. PMID: 26637976 | PMCID: PMC4678431
  • Soccio R, Chen E, Rajapurkar S, Safabakhsh P, Marinis J, Dispirito J, Emmett M, Briggs E, Fang B, Everett L, Lim H, Won K, Steger D, Wu Y, Civelek M, Voight B, Lazar M. Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo. Cell. 2015;162(1): 33-44. PMID: 26140591 | PMCID: PMC4493773
  • Wu C, Huang R, Kuo C, Kumar S, Kim C, Lin Y, Chen Y, Birukova A, Birukov K, Dulin N, Civelek M, Lusis A, Loyer X, Tedgui A, Dai G, Jo H, Fang Y. Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces. Circulation research. 2015;117(4): e41-53. PMID: 26034042 | PMCID: PMC4522239
  • Civelek M, Lusis A. From hairballs to an understanding of transendothelial migration of monocytes in atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2014;34(9): 1809-10. PMID: 25142882 | PMCID: PMC4142522
  • Germain M, Pezzolesi M, Sandholm N, McKnight A, Susztak K, Lajer M, Forsblom C, Marre M, Parving H, Rossing P, Toppila I, Skupien J, Roussel R, Ko Y, Ledo N, Folkersen L, Civelek M, Maxwell A, Tregouet D, Groop P, 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. Diabetologia. 2014;58(3): 543-8. PMID: 25476525
  • Iatan I, Choi H, Ruel I, Reddy M, Kil H, Lee J, Odeh M, Salah Z, Abu-Remaileh M, Weissglas-Volkov D, Nikkola E, Civelek M, Awan Z, Croce C, Aqeilan R, Pajukanta P, Aldaz C, Genest J. The WWOX gene modulates high-density lipoprotein and lipid metabolism. Circulation. Cardiovascular genetics. 2014;7(4): 491-504. PMID: 24871327 | PMCID: PMC4315188
  • Mäkinen V, Civelek M, Meng Q, Zhang B, Zhu J, Levian C, Huan T, Segrè A, Ghosh S, Vivar J, Nikpay M, Stewart A, Nelson C, Willenborg C, Erdmann J, Blakenberg S, O'Donnell C, März W, Laaksonen R, Epstein S, Kathiresan S, Shah S, Hazen S, Reilly M, Lusis A, Samani N, Schunkert H, Quertermous T, McPherson R, Yang X, Assimes T. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease. PLoS genetics. 2014;10(7): e1004502. PMID: 25033284 | PMCID: PMC4102418
  • Romay M, Che N, Becker S, Pouldar D, Hagopian R, Xiao X, Lusis A, Berliner J, Civelek M. Regulation of NF-κB signaling by oxidized glycerophospholipid and IL-1β induced miRs-21-3p and -27a-5p in human aortic endothelial cells. Journal of lipid research. 2014;56(1): 38-50. PMID: 25327529 | PMCID: PMC4274069
  • Civelek M, Hagopian R, Pan C, Che N, Yang W, Kayne P, Saleem N, Cederberg H, Kuusisto J, Gargalovic P, Kirchgessner T, Laakso M, Lusis A. Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits. Human molecular genetics. 2013;22(15): 3023-37. PMID: 23562819 | PMCID: PMC3699064
  • Civelek M, Lusis A. Systems genetics approaches to understand complex traits. Nature reviews. Genetics. 2013;15(1): 34-48. PMID: 24296534 | PMCID: PMC3934510
  • Davies P, Civelek M, Fang Y, Fleming I. The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovascular research. 2013;99(2): 315-27. PMID: 23619421 | PMCID: PMC3695748
  • Erbilgin A, Civelek M, Romanoski C, Pan C, Hagopian R, Berliner J, Lusis A. Identification of CAD candidate genes in GWAS loci and their expression in vascular cells. Journal of lipid research. 2013;54(7): 1894-905. PMID: 23667179 | PMCID: PMC3679391
  • Mahendran Y, Vangipurapu J, Cederberg H, Stancáková A, Pihlajamäki J, Soininen P, Kangas A, Paananen J, Civelek M, Saleem N, Pajukanta P, Lusis A, Bonnycastle L, Morken M, Collins F, Mohlke K, 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. Diabetes. 2013;62(10): 3618-26. PMID: 23557707 | PMCID: PMC3781437
  • Parks B, Nam E, Org E, Kostem E, Norheim F, Hui S, Pan C, Civelek M, Rau C, Bennett B, Mehrabian M, Ursell L, He A, Castellani L, Zinker B, Kirby M, Drake T, Drevon C, Knight R, Gargalovic P, Kirchgessner T, Eskin E, Lusis A. Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell metabolism. 2013;17(1): 141-52. PMID: 23312289 | PMCID: PMC3545283
  • de Aguiar Vallim T, Tarling E, Kim T, Civelek M, Baldán Á, Esau C, Edwards P. MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor. Circulation research. 2013;112(12): 1602-12. PMID: 23519696 | PMCID: PMC3995747
  • Ghazalpour A, Rau C, Farber C, Bennett B, Orozco L, van Nas A, Pan C, Allayee H, Beaven S, Civelek M, Davis R, Drake T, Friedman R, Furlotte N, Hui S, Jentsch J, Kostem E, Kang H, Kang E, Joo J, Korshunov V, Laughlin R, Martin L, Ohmen J, Parks B, Pellegrini M, Reue K, Smith D, Tetradis S, Wang J, Wang Y, Weiss J, Kirchgessner T, Gargalovic P, Eskin E, Lusis A, LeBoeuf R. Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits. Mammalian genome : official journal of the International Mammalian Genome Society. 2012;23(9): 680-92. PMID: 22892838 | PMCID: NIHMS416512
  • Haas B, Horvath S, Pietiläinen K, Cantor R, 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 C, Pajukanta P. Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes. BMC medical genomics. 2012;5 61. PMID: 23217153 | PMCID: PMC3543280
  • Kim J, Deluna A, Mungrue I, Vu C, Pouldar D, Civelek M, Orozco L, Wu J, Wang X, Charugundla S, Castellani L, Rusek M, Jakubowski H, Jakobowski H, Lusis A. Effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice. Circulation. 2012;126(15): 1896-906. PMID: 22952318 | PMCID: PMC3608429
  • Stancáková A, Civelek M, Saleem N, Soininen P, Kangas A, Cederberg H, Paananen J, Pihlajamäki J, Bonnycastle L, Morken M, Boehnke M, Pajukanta P, Lusis A, Collins F, 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. Diabetes. 2012;61(7): 1895-902. PMID: 22553379 | PMCID: PMC3379649
  • Civelek M, Lusis A. Conducting the metabolic syndrome orchestra. Nature genetics. 2011;43(6): 506-8. PMID: 21614088 | PMCID: PMC3934506
  • Civelek M, Manduchi E, Grant G, Stoeckert C, Davies P. Discovery approaches to UPR in athero-susceptible endothelium in vivo. Methods in enzymology. 2011;489 109-26. PMID: 21266227 | PMCID: PMC3833809
  • Civelek M, Manduchi E, Riley R, Stoeckert C, Davies P. Coronary artery endothelial transcriptome in vivo: identification of endoplasmic reticulum stress and enhanced reactive oxygen species by gene connectivity network analysis. Circulation. Cardiovascular genetics. 2011;4(3): 243-52. PMID: 21493819 | PMCID: PMC3116084
  • Romanoski C, Che N, Yin F, Mai N, Pouldar D, Civelek M, Pan C, Lee S, Vakili L, Yang W, Kayne P, Mungrue I, Araujo J, Berliner J, Lusis A. Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1. Circulation research. 2011;109(5): e27-41. PMID: 21737788 | PMCID: PMC3163234
  • Davies P, Civelek M. Endoplasmic reticulum stress, redox, and a proinflammatory environment in athero-susceptible endothelium in vivo at sites of complex hemodynamic shear stress. Antioxidants & redox signaling. 2010;15(5): 1427-32. PMID: 21126204 | PMCID: PMC3144426
  • Davies P, Civelek M, Fang Y, Guerraty M, Passerini A. Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo. Seminars in thrombosis and hemostasis. 2010;36(3): 265-75. PMID: 20533180 | PMCID: PMC3817717
  • Fang Y, Shi C, Manduchi E, Civelek M, Davies P. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(30): 13450-5. PMID: 20624982 | PMCID: PMC2922125
  • Civelek M, Grant G, Irolla C, Shi C, Riley R, Chiesa O, Stoeckert C, Karanian J, Pritchard W, Davies P. Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo. American journal of physiology. Heart and circulatory physiology. 2009;298(1): H163-70. PMID: 19897713 | PMCID: PMC2806137
  • Civelek M, Manduchi E, Riley R, Stoeckert C, Davies P. Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circulation research. 2009;105(5): 453-61. PMID: 19661457 | PMCID: PMC2746924
  • Civelek M, Ainslie K, Garanich J, Tarbell J. Smooth muscle cells contract in response to fluid flow via a Ca2+-independent signaling mechanism. Journal of applied physiology (Bethesda, Md. : 1985). 2002;93(6): 1907-17. PMID: 12391063
  • Sharma R, Yellowley C, Civelek M, Ainslie K, Hodgson L, Tarbell J, Donahue H. Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow. Annals of biomedical engineering. 2002;30(3): 371-8. PMID: 12051621 | PMCID: PMC4472337