Clint L. Miller

GetPhoto.ashx?photo=cm6bt_1378

Primary Appointment

Assistant Professor, Public Health Sciences

Education

  • PhD, Pharmacology, University of Rochester
  • Postdoc, Human Genetics, Stanford University

Research Disciplines

Biochemistry, Bioinformatics and Genomics, Cardiovascular Biology, Computational Biology, Epigenetics, Experimental Pathology, Genetics, Molecular Biology, Molecular Pharmacology, Physiology

Research Interests

Genetic variation, Complex diseases, Coronary artery disease, Genomics, Epigenomics, Regulatory mechanisms, Vascular biology, Pharmacology and Physiology

Research Description

My laboratory's research focus involves the application of modern genomics and bioinformatics approaches to unravel complex and rare cardiovascular diseases. By integrating large-scale human genetic association and whole genome sequencing data with multi-omic profiles and clinically-relevant models, our work seeks to better understand causal disease mechanisms. We are dissecting the role of genetic and drug perturbations on vascular wall processes during atherosclerosis progression. We are also studying gene-gene and gene-environment interactions at the molecular level to further inform translational targeting of multiple risk loci.

Training

  • Basic Cardiovascular Research Training Grant

Selected Publications

Wirka RC, Wagh D, Paik DT, Pjanic M, Nguyen T, Miller CL, Kundu R, Nagao M, Coller J, Koyano TK, Fong R, Woo YJ, Liu B, Montgomery SB, Wu JC, Zhu K, Chang R, Alamprese M, Tallquist MD, Kim JB, Quertermous T, Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis., 2019; Nature medicine. 25(8) 1280-1289. PMID: 31359001

Turner AW, Wong D, Khan MD, Dreisbach CN, Palmore M, Miller CL, Multi-Omics Approaches to Study Long Non-coding RNA Function in Atherosclerosis., 2019; Frontiers in cardiovascular medicine. 6() 9. PMID: 30838214 | PMCID: PMC6389617

Zhao Q, Wirka R, Nguyen T, Nagao M, Cheng P, Miller CL, Kim JB, Pjanic M, Quertermous T, TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression., 2019; Genome medicine. 11(1) 23. PMID: 31014396 | PMCID: PMC6480881

Wong D, Turner AW, Miller CL, Genetic Insights Into Smooth Muscle Cell Contributions to Coronary Artery Disease., 2019; Arteriosclerosis, thrombosis, and vascular biology. 39(6) 1006-1017. PMID: 31043074

Jaffré F, Miller CL, Schänzer A, Evans T, Roberts AE, Hahn A, Kontaridis MI, iPSC-Derived Cardiomyocytes Reveal Aberrant ERK5 and MEK1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome., 2019; Circulation. () . PMID: 31163979

Iyer D, Zhao Q, Wirka R, Naravane A, Nguyen T, Liu B, Nagao M, Cheng P, Miller CL, Kim JB, Pjanic M, Quertermous T, Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk., 2018; PLoS genetics. 14(10) e1007681. PMID: 30307970 | PMCID: PMC6198989

Kojima Y, Werner N, Ye J, Nanda V, Tsao N, Wang Y, Flores AM, Miller CL, Weissman I, Deng H, Xu B, Dalman RL, Eken SM, Pelisek J, Li Y, Maegdefessel L, Leeper NJ, Proefferocytic Therapy Promotes Transforming Growth Factor-β Signaling and Prevents Aneurysm Formation., 2018; Circulation. 137(7) 750-753. PMID: 29440201 | PMCID: PMC5819616

Nanda V, Wang T, Pjanic M, Liu B, Nguyen T, Matic LP, Hedin U, Koplev S, Ma L, Franzén O, Ruusalepp A, Schadt EE, Björkegren JLM, Montgomery SB, Snyder MP, Quertermous T, Leeper NJ, Miller CL, Functional regulatory mechanism of smooth muscle cell-restricted LMOD1 coronary artery disease locus., 2018; PLoS genetics. 14(11) e1007755. PMID: 30444878 | PMCID: PMC6268002

Liu B, Pjanic M, Wang T, Nguyen T, Gloudemans M, Rao A, Castano VG, Nurnberg S, Rader DJ, Elwyn S, Ingelsson E, Montgomery SB, Miller CL, Quertermous T, Genetic Regulatory Mechanisms of Smooth Muscle Cells Map to Coronary Artery Disease Risk Loci., 2018; American journal of human genetics. 103(3) 377-388. PMID: 30146127 | PMCID: PMC6128252

Turner AW, Wong D, Dreisbach CN, Miller CL, GWAS Reveal Targets in Vessel Wall Pathways to Treat Coronary Artery Disease., 2018; Frontiers in cardiovascular medicine. 5() 72. PMID: 29988570 | PMCID: PMC6026658

Wang Z, Civelek M, Miller CL, Sheffield NC, Guertin MJ, Zang C, BART: a transcription factor prediction tool with query gene sets or epigenomic profiles., 2018; Bioinformatics (Oxford, England). 34(16) 2867-2869. PMID: 29608647 | PMCID: PMC6084568

Kim JB, Pjanic M, Nguyen T, Miller CL, Iyer D, Liu B, Wang T, Sazonova O, Carcamo-Orive I, Matic LP, Maegdefessel L, Hedin U, Quertermous T, TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells., 2017; PLoS genetics. 13(5) e1006750. PMID: 28481916 | PMCID: PMC5439967

Miller CL, Leeper NJ, Genome-Wide Association Studies Candidate Gene to Dual Modifier of Nonalcoholic Steatohepatitis and Atherosclerosis., 2017; JACC. Basic to translational science. 1(7) 680-683. PMID: 28603781 | PMCID: PMC5465816

Pjanic M, Miller CL, Wirka R, Kim JB, DiRenzo DM, Quertermous T, Genetics and Genomics of Coronary Artery Disease., 2016; Current cardiology reports. 18(10) 102. PMID: 27586139

Kojima Y, Volkmer JP, McKenna K, Civelek M, Lusis AJ, Miller CL, Direnzo D, Nanda V, Ye J, Connolly AJ, Schadt EE, Quertermous T, Betancur P, Maegdefessel L, Matic LP, Hedin U, Weissman IL, Leeper NJ, CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis., 2016; Nature. () . PMID: 27437576 | PMCID: PMC4980260

Miller CL, Pjanic M, Wang T, Nguyen T, Cohain A, Lee JD, Perisic L, Hedin U, Kundu RK, Majmudar D, Kim JB, Wang O, Betsholtz C, Ruusalepp A, Franzén O, Assimes TL, Montgomery SB, Schadt EE, Björkegren JL, Quertermous T, Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci., 2016; Nature communications. 7() 12092. PMID: 27386823 | PMCID: PMC4941121

Perisic Matic L, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller CL, Ericsson I, Röhl S, Kronqvist M, Aldi S, Magné J, Paloschi V, Vesterlund M, Li Y, Jin H, Diez MG, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, Odeberg J, VukojeviÄ V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson GK, Lindeman JH, Eriksson P, Quertermous T, Hamsten A, Hedin U, Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM., 2016; Arteriosclerosis, thrombosis, and vascular biology. 36(9) 1947-61. PMID: 27470516

Knight WE, Chen S, Zhang Y, Oikawa M, Wu M, Zhou Q, Miller CL, Cai Y, Mickelsen DM, Moravec C, Small EM, Abe J, Yan C, PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction., 2016; Proceedings of the National Academy of Sciences of the United States of America. () . PMID: 27791092 | PMCID: PMC5111646

Nurnberg ST, Cheng K, Raiesdana A, Kundu R, Miller CL, Kim JB, Arora K, Carcamo-Oribe I, Xiong Y, Tellakula N, Nanda V, Murthy N, Boisvert WA, Hedin U, Perisic L, Aldi S, Maegdefessel L, Pjanic M, Owens GK, Tallquist MD, Quertermous T, Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap., 2015; PLoS genetics. 11(5) e1005155. PMID: 26020946 | PMCID: PMC4447275

Dewey FE, Grove ME, Priest JR, Waggott D, Batra P, Miller CL, Wheeler M, Zia A, Pan C, Karzcewski KJ, Miyake C, Whirl-Carrillo M, Klein TE, Datta S, Altman RB, Snyder M, Quertermous T, Ashley EA, Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data., 2015; PLoS genetics. 11(10) e1005496. PMID: 26448358 | PMCID: PMC4598191

Perez MV, Pavlovic A, Shang C, Wheeler MT, Miller CL, Liu J, Dewey FE, Pan S, Thanaporn PK, Absher D, Brandimarto J, Salisbury H, Chan K, Mukherjee R, Konadhode RP, Myers RM, Sedehi D, Scammell TE, Quertermous T, Cappola T, Ashley EA, Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure., 2015; Journal of the American College of Cardiology. 66(22) 2522-33. PMID: 26653627

Miller CL, Pjanic M, Quertermous T, From Locus Association to Mechanism of Gene Causality: The Devil Is in the Details., 2015; Arteriosclerosis, thrombosis, and vascular biology. 35(10) 2079-2080. PMID: 26399919 | PMCID: PMC4594207

Sazonova O, Zhao Y, Nürnberg S, Miller C, Pjanic M, Castano VG, Kim JB, Salfati EL, Kundaje AB, Bejerano G, Assimes T, Yang X, Quertermous T, Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci., 2015; PLoS genetics. 11(5) e1005202. PMID: 26020271 | PMCID: PMC4447360

Miller CL, Haas U, Diaz R, Leeper NJ, Kundu RK, Patlolla B, Assimes TL, Kaiser FJ, Perisic L, Hedin U, Maegdefessel L, Schunkert H, Erdmann J, Quertermous T, Sczakiel G, Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation., 2014; PLoS genetics. 10(3) e1004263. PMID: 24676100 | PMCID: PMC3967965

Kojima Y, Downing K, Kundu R, Miller C, Dewey F, Lancero H, Raaz U, Perisic L, Hedin U, Schadt E, Maegdefessel L, Quertermous T, Leeper NJ, Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis., 2014; The Journal of clinical investigation. 124(3) 1083-97. PMID: 24531546 | PMCID: PMC3938254

Miller CL, Assimes TL, Montgomery SB, Quertermous T, Dissecting the causal genetic mechanisms of coronary heart disease., 2014; Current atherosclerosis reports. 16(5) 406. PMID: 24623178 | PMCID: PMC4015632

Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nürnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T, Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus., 2013; PLoS genetics. 9(7) e1003652. PMID: 23874238 | PMCID: PMC3715442

Oikawa M, Wu M, Lim S, Knight WE, Miller CL, Cai Y, Lu Y, Blaxall BC, Takeishi Y, Abe J, Yan C, Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury., 2013; Journal of molecular and cellular cardiology. 64() 11-9. PMID: 23988739 | PMCID: PMC3869570

Leeper NJ, Raiesdana A, Kojima Y, Kundu RK, Cheng H, Maegdefessel L, Toh R, Ahn GO, Ali ZA, Anderson DR, Miller CL, Roberts SC, Spin JM, de Almeida PE, Wu JC, Xu B, Cheng K, Quertermous M, Kundu S, Kortekaas KE, Berzin E, Downing KP, Dalman RL, Tsao PS, Schadt EE, Owens GK, Quertermous T, Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation., 2012; Arteriosclerosis, thrombosis, and vascular biology. 33(1) e1-e10. PMID: 23162013 | PMCID: PMC3569043

Miller CL, Cai Y, Oikawa M, Thomas T, Dostmann WR, Zaccolo M, Fujiwara K, Yan C, Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart., 2011; Basic research in cardiology. 106(6) 1023-39. PMID: 22012077 | PMCID: PMC4114346

Cai Y, Miller CL, Nagel DJ, Jeon KI, Lim S, Gao P, Knight PA, Yan C, Cyclic nucleotide phosphodiesterase 1 regulates lysosome-dependent type I collagen protein degradation in vascular smooth muscle cells., 2010; Arteriosclerosis, thrombosis, and vascular biology. 31(3) 616-23. PMID: 21148428 | PMCID: PMC4114343

Miller CL, Yan C, Targeting cyclic nucleotide phosphodiesterase in the heart: therapeutic implications., 2010; Journal of cardiovascular translational research. 3(5) 507-15. PMID: 20632220 | PMCID: PMC2966469

Jeon KI, Jono H, Miller CL, Cai Y, Lim S, Liu X, Gao P, Abe J, Li JD, Yan C, Ca2+/calmodulin-stimulated PDE1 regulates the beta-catenin/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cells., 2010; The FEBS journal. 277(24) 5026-39. PMID: 21078118 | PMCID: PMC3059601

Miller CL, Oikawa M, Cai Y, Wojtovich AP, Nagel DJ, Xu X, Xu H, Florio V, Rybalkin SD, Beavo JA, Chen YF, Li JD, Blaxall BC, Abe J, Yan C, Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy., 2009; Circulation research. 105(10) 956-64. PMID: 19797176 | PMCID: PMC2803071

Yan C, Miller CL, Abe J, Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart., 2007; Circulation research. 100(4) 489-501. PMID: 17332439 | PMCID: PMC4115784