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Robert Wirka, MD

Assistant Professor of Medicine and Cell Biology and Physiology, Division of Cardiology

Specialty Areas

Clinical: General Cardiology
Research: Genetics/Genomics, Cell Biology

Education and Experience

BS: University of Wisconsin – Madison, 2004; MD: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 2010; Internal Medicine Residency: University of California – San Francisco, 2010-2013; Cardiology Fellowship: Stanford University, 2013-2016; Postdoctoral Fellowship: Stanford University, 2016-2018; Instructor: Stanford University, 2018-2020; Assistant Professor of Medicine and Cell Biology and Physiology: University of North Carolina 2020-present

Clinical and Research Interests

Genetics/Genomics, Cell Biology

Personal Statement

I am a physician-scientist who uses human genetics to uncover new mechanisms driving coronary artery disease (CAD). As a cardiologist, I see the devastation this disease continues to cause, despite our current therapies. This has motivated me to study the molecular drivers of this disease, with the goal of identifying new therapeutic targets that can reduce the burden of CAD. By studying how the genomes of patients with CAD differ from healthy people, scientists have identified signals in the human genome that point to the most critical genes and pathways driving CAD. Starting with these genetic signals, my lab 1) identifies the genes underlying these signals, 2) studies how these genes affect coronary artery biology during disease, using mouse models and human vascular samples, 3) identifies the molecular pathways affected and 4) determines how these pathways converge, like spokes on a wheel, to the central drivers of CAD. By prioritizing the study of genes and pathways we know are the most critical in driving clinical CAD, we have the best chance at developing effective therapies to mitigate this devastating disease.

Selected Bibliography

Pedroza AJ, TashimaY, Shad R, Cheng P, Wirka R, Churovich S, Nakamura K, Yokoyama N, Cui JZ, Iosef C, Hiesinger W, Quertermous T, Fischbein MP. “Single-Cell Transcriptomic Profiling of Vascular Smooth Muscle Cell Phenotype Modulation in Marfan Syndrome Aortic Aneurysm” Arterioscler Thromb Vasc Biol., 2020 Sep. PMID: 32698686

Zhao Q, Dacre M, Nguyen T, Pjanic M, Liu B, Iyer D, Cheng P, Wirka R, Kim JB, Fraser HB, Quertermous T. “Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping”. Genome Biol., 2020 Jun 8. PMCID: PMC7278146

Kim JB, Zhao Q, Nguyen T, Pjanic M, Cheng P, Wirka R, Travisano S, Nagao M, Kundu R, Quertermous R. “Environment-Sensing Aryl Hydrocarbon Receptor Inhibits the Chondrogenic Fate of Modulated Smooth Muscle Cells in Atherosclerotic Lesions”. Circulation, 2020 Aug 11. PMID: 32441123

Rykaczewska U, Suur BE, Röhl S, Razuvaev A, Lengquist M, Sabater-Lleal M, van der Laan SW, Miller CL, Wirka RC, Kronqvist M, Gonzalez Diez M, Vesterlund M, Gillgren P, Odeberg J, Lindeman JH, Veglia F, Humphries SE, de Faire U, Baldassarre D, Tremoli E; IMPROVE study group, Lehtiö J, Hansson GK, Paulsson-Berne G, Pasterkamp G, Quertermous T, Hamsten A, Eriksson P, Hedin U, Matic L “PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling”. Circulation Research, 2020 Feb 28. PMID 31893970

Flores AM, Hosseini-Nassab N, Jarr KU, Ye J, Zhu X, Wirka R, Koh AL, Tsantilas P, Wang Y, Nanda V, Kojima Y, Zeng Y, Lotfi M, Sinclair R, Weissman IL, Ingelsson E, Smith BR, Leeper NJ. “Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis”. Nat Nanotechnol. 2020 Feb 15. PMID 31988506

Nagao M, Lyu Q, Zhao Q, Wirka RC, Bagga J, Nguyen T, Cheng P, Kim JB, Pjanic M, Miano JM, Quertermous T. “Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway”. Circulation Research, 2020 Feb 14. PMID 31815603

Nurnberg ST, Guerraty MA, Wirka RC, Rao HS, Pjanic M, Norton S, Serrano F, Perisic L, Elwyn S, Pluta J, Zhao W, Testa S, Park Y, Nguyen T, Ko YA, Wang T, Hedin U, Sinha S, Barash Y, Brown CD, Quertermous T, Rader DJ. “Genomic profiling of human vascular cells identifies TWIST1 as a causal gene for common vascular diseases”. PLoS Genetics 2020 Jan 9. PMID 31917787

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”. Nature Medicine, 2019 July 29. PMID: 31359001

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”. Genome Med. 2019 May 2. PMCID 6480881

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”. PLoS Genet. 2018 Oct 11;14(10):e1007681. PMID 30307970

Paik DT, Tian L, Lee J, Sayed N, Chen IY, Rhee S, Rhee JW, Kim Y, Wirka RC, Buikema JW, Wu SM, Red-Horse K, Quertermous T, Wu JC. “Large-Scale Single-Cell RNA-Seq Reveals Molecular Signatures of Heterogeneous Populations of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells”. Circ Res. 2018 Jul 9. pii:CIRCRESAHA.118.312913. PMID 29986945

Wirka RC, Pjanic M, Quertermous T. “Advances in Transcriptomics: Investigating Cardiovascular Disease at Unprecedented Resolution”. Circ Res. 2018 Apr 27;122(9):1200-1220. PMID 29700068

Wirka RC, Quertermous T. “Circulating peptide prevents preeclampsia”. Science. 2017 Aug 18;357(6352):643-644. PMID 28818928

Xu B, Fu Y, Liu Y, Agvanian S, Wirka RC, Baum R, Zhou K, Shaw RM, Hong T. “The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles”. PLoS Biol. 2017 Aug 14;15(8). PMID 28806752

Pjanic M, Miller CL, Wirka R, Kim JB, DiRenzo DM, Quertermous T. “Genetics and genomics of coronary artery disease”. Curr Cardiol Rep. 2016(Oct 18). PMID 27586139

Tchou GD, Wirka RC, Van Wagoner DR, Barnard J, Chung MK, Smith JD. “Low prevalence of connexin-40 gene variants in atrial tissues and blood from atrial fibrillation subjects”. BMC Med Genet, 2012(Nov 7). PMID 23134779

Kim JJ, Vaziri SA, Rini BI, Elson P, Garcia JA, Wirka RC, Dreicer R, Ganapathi MK, Ganapathi R. “Association of VEGF and VEGFR2 Single Nucleotide Polymorphisms With Hypertension and Clinical Outcome in Metastatic Clear Cell Renal Cell Carcinoma Patients Treated With Sunitinib Association of VEGF and VEGFR2 Single Nucleotide Polymorphisms With Hypertension and Clinical Outcome in Metastatic Clear Cell Renal Cell Carcinoma Patients Treated With Sunitinib”. Cancer, 2011(Aug 31). PMID 21882181

Wirka RC, Gore S, Van Wagoner DR, Barnard J, Arking DE, Lubitz SA, Benjamin EJ, Alonzo A, Ellinor PT, Chung MK, Smith JD. ” A Common Connexin-40 Gene Promoter Variant Affects Connexin-40 Expression in Human Atria and Is Associated with Atrial Fibrillation”. Circulation Arrhythmia and Electrophysiology, 2010(Nov 13). PMID 21076161

https://www.ncbi.nlm.nih.gov/myncbi/1DI_a9UA67GQJ/bibliography/public/

 

 

  • Phone Number

    Office: 919-445-1300 (Office Phone)

  • Address

    McAllister Heart Institute

    111 Mason Farm Road, MBRB 3312B

    Chapel Hill, NC 27599-7126