Clint L. Miller

Education

  • PhD, University of Rochester
  • Postdoc, Stanford University

Contact

Research Interest(s)

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 to unravel complex human diseases. By integrating large-scale human genetic association data with multi-omic profiling 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.

Selected Publications

  • Kim J, Pjanic M, Nguyen T, Miller C, Iyer D, Liu B, Wang T, Sazonova O, Carcamo-Orive I, Matic L, 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. PLoS genetics. 2017;13(5): e1006750. PMID: 28481916 | PMCID: PMC5439967
  • Miller C, Leeper N. Genome-Wide Association Studies Candidate Gene to Dual Modifier of Nonalcoholic Steatohepatitis and Atherosclerosis. JACC. Basic to translational science. 2017;1(7): 680-683. PMID: 28603781 | PMCID: PMC5465816
  • Knight W, Chen S, Zhang Y, Oikawa M, Wu M, Zhou Q, Miller C, Cai Y, Mickelsen D, Moravec C, Small E, Abe J, Yan C. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction. Proceedings of the National Academy of Sciences of the United States of America. 2016. PMID: 27791092 | PMCID: PMC5111646
  • 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
  • Miller C, Pjanic M, Wang T, Nguyen T, Cohain A, Lee J, Perisic L, Hedin U, Kundu R, Majmudar D, Kim J, Wang O, Betsholtz C, Ruusalepp A, Franzén O, Assimes T, Montgomery S, Schadt E, Björkegren J, Quertermous T. Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. Nature communications. 2016;7 12092. PMID: 27386823 | PMCID: PMC4941121
  • Perisic Matic L, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller C, Ericsson I, Röhl S, Kronqvist M, Aldi S, Magné J, Paloschi V, Vesterlund M, Li Y, Jin H, Diez M, Roy J, Baldassarre D, Veglia F, Humphries S, de Faire U, Tremoli E, Odeberg J, Vukojević V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson G, Lindeman J, 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. Arteriosclerosis, thrombosis, and vascular biology. 2016;36(9): 1947-61. PMID: 27470516
  • Pjanic M, Miller C, Wirka R, Kim J, DiRenzo D, Quertermous T. Genetics and Genomics of Coronary Artery Disease. Current cardiology reports. 2016;18(10): 102. PMID: 27586139
  • Dewey F, Grove M, Priest J, Waggott D, Batra P, Miller C, Wheeler M, Zia A, Pan C, Karzcewski K, Miyake C, Whirl-Carrillo M, Klein T, Datta S, Altman R, Snyder M, Quertermous T, Ashley E. Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data. PLoS genetics. 2015;11(10): e1005496. PMID: 26448358 | PMCID: PMC4598191
  • Miller C, Pjanic M, Quertermous T. From Locus Association to Mechanism of Gene Causality: The Devil Is in the Details. Arteriosclerosis, thrombosis, and vascular biology. 2015;35(10): 2079-2080. PMID: 26399919 | PMCID: PMC4594207
  • Nurnberg S, Cheng K, Raiesdana A, Kundu R, Miller C, Kim J, Arora K, Carcamo-Oribe I, Xiong Y, Tellakula N, Nanda V, Murthy N, Boisvert W, Hedin U, Perisic L, Aldi S, Maegdefessel L, Pjanic M, Owens G, Tallquist M, Quertermous T. Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. PLoS genetics. 2015;11(5): e1005155. PMID: 26020946 | PMCID: PMC4447275
  • Perez M, Pavlovic A, Shang C, Wheeler M, Miller C, Liu J, Dewey F, Pan S, Thanaporn P, Absher D, Brandimarto J, Salisbury H, Chan K, Mukherjee R, Konadhode R, Myers R, Sedehi D, Scammell T, Quertermous T, Cappola T, Ashley E. Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure. Journal of the American College of Cardiology. 2015;66(22): 2522-33. PMID: 26653627
  • Sazonova O, Zhao Y, Nürnberg S, Miller C, Pjanic M, Castano V, Kim J, Salfati E, Kundaje A, 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. PLoS genetics. 2015;11(5): e1005202. PMID: 26020271 | PMCID: PMC4447360
  • 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 N. Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis. The Journal of clinical investigation. 2014;124(3): 1083-97. PMID: 24531546 | PMCID: PMC3938254
  • Miller C, Assimes T, Montgomery S, Quertermous T. Dissecting the causal genetic mechanisms of coronary heart disease. Current atherosclerosis reports. 2014;16(5): 406. PMID: 24623178 | PMCID: PMC4015632
  • Miller C, Haas U, Diaz R, Leeper N, Kundu R, Patlolla B, Assimes T, Kaiser F, 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. PLoS genetics. 2014;10(3): e1004263. PMID: 24676100 | PMCID: PMC3967965
  • Miller C, Anderson D, Kundu R, Raiesdana A, Nürnberg S, Diaz R, Cheng K, Leeper N, Chen C, Chang I, Schadt E, Hsiung C, Assimes T, Quertermous T. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. PLoS genetics. 2013;9(7): e1003652. PMID: 23874238 | PMCID: PMC3715442
  • Oikawa M, Wu M, Lim S, Knight W, Miller C, Cai Y, Lu Y, Blaxall B, Takeishi Y, Abe J, Yan C. Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury. Journal of molecular and cellular cardiology. 2013;64 11-9. PMID: 23988739 | PMCID: PMC3869570
  • Leeper N, Raiesdana A, Kojima Y, Kundu R, Cheng H, Maegdefessel L, Toh R, Ahn G, Ali Z, Anderson D, Miller C, Roberts S, Spin J, de Almeida P, Wu J, Xu B, Cheng K, Quertermous M, Kundu S, Kortekaas K, Berzin E, Downing K, Dalman R, Tsao P, Schadt E, Owens G, Quertermous T. Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arteriosclerosis, thrombosis, and vascular biology. 2012;33(1): e1-e10. PMID: 23162013 | PMCID: PMC3569043
  • Miller C, Cai Y, Oikawa M, Thomas T, Dostmann W, Zaccolo M, Fujiwara K, Yan C. Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Basic research in cardiology. 2011;106(6): 1023-39. PMID: 22012077 | PMCID: PMC4114346
  • Cai Y, Miller C, Nagel D, Jeon K, Lim S, Gao P, Knight P, Yan C. Cyclic nucleotide phosphodiesterase 1 regulates lysosome-dependent type I collagen protein degradation in vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology. 2010;31(3): 616-23. PMID: 21148428 | PMCID: PMC4114343
  • Jeon K, Jono H, Miller C, Cai Y, Lim S, Liu X, Gao P, Abe J, Li J, Yan C. Ca2+/calmodulin-stimulated PDE1 regulates the beta-catenin/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cells. The FEBS journal. 2010;277(24): 5026-39. PMID: 21078118 | PMCID: PMC3059601
  • Miller C, Yan C. Targeting cyclic nucleotide phosphodiesterase in the heart: therapeutic implications. Journal of cardiovascular translational research. 2010;3(5): 507-15. PMID: 20632220 | PMCID: PMC2966469
  • Miller C, Oikawa M, Cai Y, Wojtovich A, Nagel D, Xu X, Xu H, Florio V, Rybalkin S, Beavo J, Chen Y, Li J, Blaxall B, Abe J, Yan C. Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy. Circulation research. 2009;105(10): 956-64. PMID: 19797176 | PMCID: PMC2803071
  • Yan C, Miller C, Abe J. Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart. Circulation research. 2007;100(4): 489-501. PMID: 17332439 | PMCID: PMC4115784