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Gary K. Owens

Gary K. Owens

Robert M. Berne Professor of Cardiovascular Research, Molecular Physiology and Biological Physics

Primary Location
PO Box 800736
Room 1322 MR5
Primary Phone Number
434.924.2652
Email
[email protected]
Website
https://www.cvrc.virginia.edu/Owens/

Bio & Overview

Identification of Factors and Mechanisms that Regulate the Stability of Late Stage Atherosclerotic Lesions and the Probability of Thromboembolic Events Including a Heart Attack or Stroke Atherothrombosis, resulting from rupture or erosion of unstable atherosclerotic plaques, is the leading cause of death worldwide. However, the mechanisms that regulate the stability of late stage atherosclerotic lesions remain poorly understood. The general dogma based on extensive human histopathology studies is that: 1) plaque composition not size is a critical determinant of late stage lesion stability and the probability of rupture or erosion and a possible heart attack or stroke; 2) plaques containing a large necrotic core, a thin fibrous cap, and large numbers of CD68+ cells relative to Acta2+ cells [presumed to be macrophages (MФ) and smooth muscle cells (SMC) respectively] are more prone to rupture or erosion; and 3) the primary role of the SMC is athero-protective by virtue of them being the primary cell type responsible for formation of a protective fibrous cap. However, several recent Nature Medicine studies1, 2 by our lab involving simultaneous SMC lineage tracing and SMC-specific knockout (KO) of the stem cell pluripotency genes Oct4 or Klf4, have provided compelling evidence challenging this dogma and showing that SMC play a much greater role in lesion pathogenesis than has been generally appreciated [see our recent review3]. For example, we showed that >80% of SMC-derived cells within advanced lesions of ApoE-/- mice fed a Western diet (WD) for 18 weeks lacked detectable expression of SMC markers such as Acta2 typically used to identify them meaning that previous studies in the field have grossly under-estimated the number of SMC-derived cells within advanced lesions. Moreover, >30% of cells previously identified as MФ within advanced mouse brachiocephalic artery (BCA) lesions and human advanced coronary artery lesions were found to be of SMC not myeloid origin meaning that previous estimates of SMC/ MФ ratios are highly inaccurate. Even more importantly, we found that SMC can play either a beneficial or detrimental role in lesion pathogenesis depending on the nature of their phenotypic/functional transitions. For example, Klf4-dependent transitions, including formation of SMC-derived MФ-marker+ foam cells1 exacerbated lesion pathogenesis whereas Oct4-dependent transitions2 were atheroprotective including being critical for migration and investment of SMC into a protective fibrous cap. Indeed, remarkably, results of RNAseq and Oct4/Klf4 CHIPseq analyses of advanced brachiocephalic lesions from SMC Klf4 versus SMC Oct4 knockout mice showed virtually completely opposite genomic signatures. Taken together, results show that SMC play an absolutely critical, even dominant role, in late stage lesion pathogenesis in that conditional loss of a single gene in SMC can completely alter lesion pathogenesis [see our recent review3]. A major focus of our current studies is to identify factors, mechanisms, and potential therapeutic targets that can promote beneficial, and/or inhibit detrimental SMC phenotypic transitions within advanced lesions and thereby promote increased plaque stability. In addition, we are determining if mutations or gene polymorphisms that are linked to increased cardiovascular disease in humans may function, at least in part, by promoting detrimental changes in SMC phenotype and their associated functions. Finally, we have initiated additional studies investigating the potential role of SMC and pericyte phenotypic transitions in the pathogenesis of microvascular disease associated with Type II diabetes/metabolic disease, and in regulation of tumor cell growth and metastasis. The latter studies, which were published in Nature Medicine4 and done in collaboration with Dr. Kaplan’s lab at NIH, showed that highly metastatic tumor cells secrete factors that circulate in blood and induce Klf4-dependent reprogramming of SMC and pericytes within metastatic niches that make them permissive for tumor cell invasion and survival. Remarkably, we found that SMC-pericyte specific knockout of the stem cell pluripotency gene Klf4 dramatically reduced tumor metastasis by >70%. Reference List:
(1) Shankman LS, Gomez D, Cherepanova OA, Salmon M, Alencar GF, Haskins RM, Swiatlowska P, Newman AA, Greene ES, Straub AC, Isakson B, Randolph GJ, Owens GK. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med 2015 May 18;21(6):628-37.
(2) Cherepanova OA, Gomez D, Shankman LS, Swiatlowska P, Williams J, Sarmento OF, Alencar GF, Hess DL, Bevard MH, Greene ES, Murgai M, Turner SD, Geng YJ, Bekiranov S, Connelly JJ, Tomilin A, Owens GK. Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nat Med 2016 May 16;22(6):657-65.
(3) Bennett MR, Sinha S, Owens GK. Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res 2016 February 19;118(4):692-702.
(4) Murgai M, Ju W, Eason M, Kline J, Beury DW, Kaczanowska S, Miettinen MM, Kruhlak M, Lei H, Shern JF, Cherepanova OA, Owens GK, Kaplan RN. KLF4-dependent perivascular cell plasticity mediates pre-metastatic niche formation and metastasis. Nat Med 2017 October;23(10):1176-90. List of Publications in Pubmed

Academic Information

Department
Molecular Physiology and Biological Physics
Academic Title
Professor

Primary Education

  • BS, Animal Science, Pennsylvania State University, 1976
  • MS, Biology and Physiology, Pennsylvania State University, 1977
  • PhD, Biology and Physiology, Pennsylvania State University, 1979
  • Postdoc, Pathology, University of Washington, Seattle, 1981

Other Appointments

  • Pathology
  • Professor, BMBG
  • Professor, MCDB
  • Professor, Medicine- Cardiovascular Medicine
  • Professor, MOMD

Other Affiliations

  • Member, Cancer Cell Signaling Program
  • Director, Cardiovascular Research Center
  • MSTP
  • Professor, BIMS

Research Interests

Identification of Factors and Mechanisms that Regulate the Stability of Late Stage Atherosclerotic Lesions and the Probability of Thromboembolic Events Including a Heart Attack or Stroke

Research Disciplines

  • Cancer Biology
  • Cardiovascular Biology
  • Epigenetics
  • Experimental Pathology
  • Physiology

Research Opportunities

  • Bioinformatics & Genomics
  • Cancer Biology
  • Cardiovascular Disease
  • Cellular and Molecular Metabolism
  • Epigenetics
  • Experimental Pathology
  • Physiological Basis of Human Disease

PhD Programs

  • Biochemistry & Molecular Genetics
  • Experimental Pathology
  • Physiology

Selected Publications

2024

Shamsuzzaman, S., Deaton, R. A., Salamon, A., Doviak, H., Serbulea, V., Milosek, V. M., . . . Owens, G. K. (2024). Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition.. Circulation. doi:10.1161/circulationaha.123.067931

Karnewar, S., Karnewar, V., Deaton, R. A., Shankman, L. S., Benavente, E. D., Williams, C. M., . . . Owens, G. K. (2024). IL-1β Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 44(6), 1379-1392. doi:10.1161/ATVBAHA.124.320800

Mocci, G., Sukhavasi, K., Ord, T., Bankier, S., Singha, P., Arasu, U. T., . . . Bjorkegren, J. L. M. (2024). Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis. CIRCULATION RESEARCH, 134(11), 1405-1423. doi:10.1161/CIRCRESAHA.123.323184

Aherrahrou, R., Baig, F., Theofilatos, K., Lue, D., Beele, A., Oerd, T., . . . Civelek, M. (2024). Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 44(4), 898-914. doi:10.1161/ATVBAHA.123.320274

Karnewar, S., Karnewar, V., Shankman, L. S., & Owens, G. K. (2024). Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality. JCI INSIGHT, 9(2). doi:10.1172/jci.insight.173863

2023

Karnewar, S., Karnewar, V., Deaton, R., Shankman, L. S., Benavente, E. D., Williams, C. M., . . . Owens, G. K. (2023). IL-1β inhibition partially negates the beneficial effects of diet-induced lipid lowering.. bioRxiv. doi:10.1101/2023.10.13.562255

Benavente, E. D., Karnewar, S., Buono, M., Mili, E., Hartman, R. J. G., Kapteijn, D., . . . den Ruijter, H. M. (2023). Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 43(10), 1836-1850. doi:10.1161/ATVBAHA.123.319325

Karnewar, S., Karnewar, V., Shankman, L. S., & Owens, G. K. (2023). Treatment of advanced atherosclerotic mice with the senolytic agent ABT-263 is associated with reduced indices of plaque stability and increased mortality.. bioRxiv. doi:10.1101/2023.07.12.548696

Benavente, E. D., Karnewar, S., Buono, M., Mili, E., Hartman, R. J. G., Kapteijn, D., . . . den Ruijter, H. M. (2023). Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques.. bioRxiv. doi:10.1101/2023.02.08.527690

Deaton, R. A., Bulut, G., Serbulea, V., Salamon, A., Shankman, L. S., Nguyen, A. T., & Owens, G. K. (2023). A New Autosomal Myh11-CreERT2 Smooth Muscle Cell Lineage Tracing and Gene Knockout Mouse Model-Brief Report. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 43(2), 203-211. doi:10.1161/ATVBAHA.122.318160

Serbulea, V., Deaton, R. A. A., & Owens, G. K. K. (2023). Old bones control smooth muscle clones. NATURE AGING, 3(1), 9-10. doi:10.1038/s43587-022-00346-1

2022

Owens, G. K., & Deaton, R. A. (2023). Response by Owens and Deaton to Letter Regarding Article, "Dichotomous Roles of Smooth Muscle Cell-Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis". ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 43(1), E64. doi:10.1161/ATVBAHA.122.318638

Owsiany, K. M., Deaton, R. A., Soohoo, K. G., Anh, T. N., & Owens, G. K. (2022). Dichotomous Roles of Smooth Muscle Cell-Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 42(8), 942-956. doi:10.1161/ATVBAHA.122.317882

Li, J., Shen, H., Owens, G. K., & Guo, L. -W. (2022). SREBP1 regulates Lgals3 activation in response to cholesterol loading. MOLECULAR THERAPY-NUCLEIC ACIDS, 28, 892-909. doi:10.1016/j.omtn.2022.05.028

Shin, J., Tkachenko, S., Chaklader, M., Pletz, C., Singh, K., Bulut, G. B., . . . Cherepanova, O. A. (2022). Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction. CARDIOVASCULAR RESEARCH, 118(11), 2458-2477. doi:10.1093/cvr/cvac036

2021

Ma, W. F., Hodonsky, C. J., Turner, A. W., Wong, D., Song, Y., Mosquera, J. V., . . . Miller, C. L. (2022). Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets. ATHEROSCLEROSIS, 340, 12-22. doi:10.1016/j.atherosclerosis.2021.11.025

Hartmann, F., Gorski, D. J., Newman, A. A. C., Homann, S., Petz, A., Owsiany, K. M., . . . Fischer, J. W. (2021). SMC-Derived Hyaluronan Modulates Vascular SMC Phenotype in Murine Atherosclerosis. CIRCULATION RESEARCH, 129(11), 992-1005. doi:10.1161/CIRCRESAHA.120.318479

Liu, M., Espinosa-Diez, C., Mahan, S., Du, M., Nguyen, A. T., Hahn, S., . . . Gomez, D. (2021). H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity. DEVELOPMENTAL CELL, 56(19), 2765-+. doi:10.1016/j.devcel.2021.09.001

Newman, A. A. C., Serbulea, V., Baylis, R. A., Shankman, L. S., Bradley, X., Alencar, G. F., . . . Owens, G. K. (2021). Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms. NATURE METABOLISM, 3(2), 166-+. doi:10.1038/s42255-020-00338-8

Hartman, R. J. G., Owsiany, K., Ma, L., Koplev, S., Hao, K., Slenders, L., . . . den Ruijter, H. M. (2021). Sex-Stratified Gene Regulatory Networks Reveal Female Key Driver Genes of Atherosclerosis Involved in Smooth Muscle Cell Phenotype Switching. CIRCULATION, 143(7), 713-726. doi:10.1161/CIRCULATIONAHA.120.051231

2020

Bulut, G. B., Alencar, G. F., Owsiany, K. M., Nguyen, A. T., Karnewar, S., Haskins, R. M., . . . Owens, G. K. (2021). KLF4 (Kruppel-Like Factor 4)-Dependent Perivascular Plasticity Contributes to Adipose Tissue inflammation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 41(1), 284-301. doi:10.1161/ATVBAHA.120.314703

Aherrahrou, R., Guo, L., Nagraj, V. P., Aguhob, A., Hinkle, J., Chen, L., . . . Civelek, M. (2020). Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells. CIRCULATION RESEARCH, 127(12), 1552-1565. doi:10.1161/CIRCRESAHA.120.317415

Ray, H. C., Corliss, B. A., Bruce, A. C., Kesting, S., Dey, P., Mansour, J., . . . Yates, P. A. (2020). Myh11+microvascular mural cells and derived mesenchymal stem cells promote retinal fibrosis. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-72875-x

Alencar, G. F., Owsiany, K. M., Karnewar, S., Sukhavasi, K., Mocci, G., Nguyen, A. T., . . . Owens, G. K. (2020). Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis. CIRCULATION, 142(21), 2045-2059. doi:10.1161/CIRCULATIONAHA.120.046672

Wang, Y., Nanda, V., Direnzo, D., Ye, J., Xiao, S., Kojima, Y., . . . Leeper, N. J. (2020). Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(27), 15818-15826. doi:10.1073/pnas.2006348117

Corliss, B. A., Ray, H. C., Doty, R. W., Mathews, C., Sheybani, N., Fitzgerald, K., . . . Peirce, S. M. (2020). Pericyte Bridges in Homeostasis and Hyperglycemia. DIABETES, 69(7), 1503-1517. doi:10.2337/db19-0471

2019

Cherepanova, O. A., Srikakulapu, P., Greene, E. S., Chaklader, M., Haskins, R. M., McCanna, M. E., . . . Owens, G. K. (2020). Novel Autoimmune IgM Antibody Attenuates Atherosclerosis in IgM Deficient Low-Fat Diet-Fed, but Not Western Diet-Fed Apoe-/- Mice. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 40(1), 206-219. doi:10.1161/ATVBAHA.119.312771

Owsiany, K. M., Alencar, G. F., & Owens, G. K. (2019). Revealing the Origins of Foam Cells in Atherosclerotic Lesions. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 39(5), 836-838. doi:10.1161/ATVBAHA.119.312557

Owens, G. K., & Pasterkamp, G. (2019). PlaqOmics Leducq Fondation Trans-Atlantic Network Defining the Roles of Smooth Muscle Cells and Other Extracellular Matrix-Producing Cells in Late-Stage Atherosclerotic Plaque Pathogenesis. CIRCULATION RESEARCH, 124(9), 1297-1299. doi:10.1161/CIRCRESAHA.119.314989

Hess, D. L., Kelly-Goss, M. R., Cherepanova, O. A., Nguyen, A. T., Baylis, R. A., Tkachenko, S., . . . Owens, G. K. (2019). Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. NATURE COMMUNICATIONS, 10. doi:10.1038/s41467-019-08811-z

Salmon, M., Schaheen, B., Spinosa, M., Montgomery, W., Pope, N. H., Davis, J. P., . . . Ailawadi, G. (2019). ZFP148 (Zinc-Finger Protein 148) Binds Cooperatively With NF-1 (Neurofibromin 1) to Inhibit Smooth Muscle Marker Gene Expression During Abdominal Aortic Aneurysm Formation (Publication with Expression of Concern. See vol. 39, 2019). ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 39(1), 73-88. doi:10.1161/ATVBAHA.118.311136

2018

Newman, A. A. C., Baylis, R. A., Hess, D. L., Griffith, S. D., Shankman, L. S., Cherepanova, O. A., & Owens, G. K. (2018). Irradiation abolishes smooth muscle investment into vascular lesions in specific vascular beds. JCI INSIGHT, 3(15). doi:10.1172/jci.insight.121017

Gomez, D., Baylis, R. A., Durgin, B. G., Newman, A. A. C., Alencar, G. F., Mahan, S., . . . Owens, G. K. (2018). Interleukin-1β has atheroprotective effects in advanced atherosclerotic lesions of mice. NATURE MEDICINE, 24(9), 1418-+. doi:10.1038/s41591-018-0124-5

Haskins, R. M., Nguyen, A. T., Alencar, G. F., Billaud, M., Kelly-Goss, M. R., Good, M. E., . . . Owens, G. K. (2018). Klf4 has an unexpected protective role in perivascular cells within the microvasculature. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 315(2), H402-H414. doi:10.1152/ajpheart.00084.2018

Starke, R. M., Thompson, J. W., Ali, M. S., Pascale, C. L., Lege, A. M., Ding, D., . . . Dumont, A. S. (2018). Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 38(3), 610-621. doi:10.1161/ATVBAHA.117.310478

Owsiany, K., Anh, N., & Owens, G. K. (2018). Vascular Smooth Muscle derived Macrophage are a Major Source of MCP1 in Atherosclerosis. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 38. doi:10.1161/atvb.38.suppl_1.582

Hess, D. L., Kelly-Goss, M. R., Cherepanova, O., Nguyen, A. T., Annex, B. H., Peirce, S. M., & Owens, G. K. (2018). Perivascular Cell-specific Knockout of the Stem Cell Pluripotency Gene Oct4 Inhibits Angiogenesis in Part by Attenuating Perivascular and Endothelial Cell Migration. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 38. doi:10.1161/atvb.38.suppl_1.008

2017

Baylis, R. A., Gomez, D., Mallat, Z., Pasterkamp, G., & Owens, G. K. (2017). The CANTOS Trial One Important Step for Clinical Cardiology but a Giant Leap for Vascular Biology. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 37(11), E174-E177. doi:10.1161/ATVBAHA.117.310097

Murgai, M., Ju, W., Eason, M., Kline, J., Beury, D. W., Kaczanowska, S., . . . Kaplan, R. N. (2017). KLF4-dependent perivascular cell plasticity mediates pre-metastatic niche formation and metastasis. NATURE MEDICINE, 23(10), 1176-+. doi:10.1038/nm.4400

Durgin, B. G., Cherepanova, O. A., Gomez, D., Karaoli, T., Alencar, G. F., Butcher, J. T., . . . Connelly, J. J. (2017). Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 312(5), H943-H958. doi:10.1152/ajpheart.00029.2017

Baylis, R. A., Gomez, D., & Owens, G. K. (2017). Shifting the Focus of Preclinical, Murine Atherosclerosis Studies From Prevention to Late-Stage Intervention. CIRCULATION RESEARCH, 120(5), 775-777. doi:10.1161/CIRCRESAHA.116.310101

DiRenzo, D., Owens, G. K., & Leeper, N. J. (2017). "Attack of the Clones" Commonalities Between Cancer and Atherosclerosis. CIRCULATION RESEARCH, 120(4), 624-626. doi:10.1161/CIRCRESAHA.116.310091

2016

Gomez, D., & Owens, G. K. (2016). Reconciling Smooth Muscle Cell Oligoclonality and Proliferative Capacity in Experimental Atherosclerosis. CIRCULATION RESEARCH, 119(12), 1262-1264. doi:10.1161/CIRCRESAHA.116.310104

Cherepanova, O. A., Gomez, D., Shankman, L. S., Swiatlowska, P., Williams, J., Sarmento, O. F., . . . Owens, G. K. (2016). Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. NATURE MEDICINE, 22(6), 657-+. doi:10.1038/nm.4109

Bennett, M. R., Sinha, S., & Owens, G. K. (2016). Vascular Smooth Muscle Cells in Atherosclerosis. CIRCULATION RESEARCH, 118(4), 692-702. doi:10.1161/CIRCRESAHA.115.306361

Shankman, L. S., Gomez, D., Cherepanova, O. A., Salmon, M., Alencar, G. F., Haskins, R. M., . . . Owens, G. K. (2016). Corrigendum: KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis.. Nature medicine, 22(2), 217. doi:10.1038/nm0216-217a

Shankman, L. S., Gomez, D., Cherepanova, O. A., Salmon, M., Alencar, G. F., Haskins, R. M., . . . Owens, G. K. (2016). KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis (vol 21, pg 628, 2015). NATURE MEDICINE, 22(2), 217. doi:10.1038/nm0216-217a

2015

Wu, J., Montaniel, K. R. C., Saleh, M. A., Xiao, L., Chen, W., Owens, G. K., . . . Harrison, D. G. (2016). Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension. HYPERTENSION, 67(2), 461-468. doi:10.1161/HYPERTENSIONAHA.115.06123

Cuttano, R., Rudini, N., Bravi, L., Corada, M., Giampietro, C., Papa, E., . . . Dejana, E. (2016). KLF4 is a key determinant in the development and progression of cerebral cavernous malformations. EMBO MOLECULAR MEDICINE, 8(1), 6-24. doi:10.15252/emmm.201505433

Gomez, D., Swiatlowska, P., & Owens, G. K. (2015). Epigenetic Control of Smooth Muscle Cell Identity and Lineage Memory. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 35(12), 2508-2516. doi:10.1161/ATVBAHA.115.305044

Nurnberg, S. T., Cheng, K., Raiesdana, A., Kundu, R., Miller, C. L., Kim, J. B., . . . Quertermous, T. (2015). Coronary artery disease associated transcription factor TCF21 regulates smooth muscle precursor cells that contribute to the fibrous cap. GENOMICS DATA, 5, 36-37. doi:10.1016/j.gdata.2015.05.007

Shankman, L. S., Gomez, D., Cherepanova, O. A., Salmon, M., Alencar, G. F., Haskins, R. M., . . . Owens, G. K. (2015). KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. NATURE MEDICINE, 21(6), 628-637. doi:10.1038/nm.3866

Nurnberg, S. T., Cheng, K., Raiesdana, A., Kundu, R., Miller, C. L., Kim, J. B., . . . Quertermous, T. (2015). Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. PLOS GENETICS, 11(5). doi:10.1371/journal.pgen.1005155

Tabas, I., Garcia-Cardena, G., & Owens, G. K. (2015). Recent insights into the cellular biology of atherosclerosis. JOURNAL OF CELL BIOLOGY, 209(1), 13-22. doi:10.1083/jcb.201412052

2014

Bhamidipati, C. M., Whatling, C. A., Mehta, G. S., Meher, A. K., Hajzus, V. A., Su, G., . . . Ailawadi, G. (2014). 5-Lipoxygenase Pathway in Experimental Abdominal Aortic Aneurysms. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 34(12), 2669-2678. doi:10.1161/ATVBAHA.114.304016

Johnston, W. F., Salmon, M., Pope, N. H., Meher, A., Su, G., Stone, M. L., . . . Ailawadi, G. (2014). Inhibition of Interleukin-1β Decreases Aneurysm Formation and Progression in a Novel Model of Thoracic Aortic Aneurysms. CIRCULATION, 130(11), S51-+. doi:10.1161/CIRCULATIONAHA.113.006800

Starke, R. M., Chalouhi, N., Jabbour, P. M., Tjoumakaris, S. I., Gonzalez, L. F., Rosenwasser, R. H., . . . Dumont, A. S. (2014). Critical role of TNF-α in cerebral aneurysm formation and progression to rupture. JOURNAL OF NEUROINFLAMMATION, 11. doi:10.1186/1742-2094-11-77

Ding, D., Starke, R. M., Dumont, A. S., Owens, G. K., Hasan, D. M., Chalouhi, N., . . . Lin, C. -L. (2014). Therapeutic Implications of Estrogen for Cerebral Vasospasm and Delayed Cerebral Ischemia Induced by Aneurysmal Subarachnoid Hemorrhage. BIOMED RESEARCH INTERNATIONAL, 2014. doi:10.1155/2014/727428

2013

Starke, R. M., Chalouhi, N., Ding, D., Raper, D. M. S., Mckisic, M. S., Owens, G. K., . . . Dumont, A. S. (2014). Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis. TRANSLATIONAL STROKE RESEARCH, 5(3), 338-346. doi:10.1007/s12975-013-0290-1

Starke, R. M., Raper, D. M. S., Ding, D., Chalouhi, N., Owens, G. K., Hasan, D. M., . . . Dumont, A. S. (2014). Tumor Necrosis Factor-α Modulates Cerebral Aneurysm Formation and Rupture. TRANSLATIONAL STROKE RESEARCH, 5(2), 269-277. doi:10.1007/s12975-013-0287-9

Salmon, M., Johnston, W. F., Woo, A., Pope, N. H., Su, G., Upchurch, G. R. J., . . . Ailawadi, G. (2013). KLF4 Regulates Abdominal Aortic Aneurysm Morphology and Deletion Attenuates Aneurysm Formation. CIRCULATION, 128(11), S163-S174. doi:10.1161/CIRCULATIONAHA.112.000238

Ali, M. S., Starke, R. M., Jabbour, P. M., Tjoumakaris, S. I., Gonzalez, L. F., Rosenwasser, R. H., . . . Dumont, A. S. (2013). TNF-α induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 33(10), 1564-1573. doi:10.1038/jcbfm.2013.109

Murgai, M., Thomas, J., Cherepanova, O., Delviks-Frankenberry, K., Deeble, P., Pathak, V. K., . . . Owens, G. (2013). Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels. RETROVIROLOGY, 10. doi:10.1186/1742-4690-10-34

Bhamidipati, C. M., Mehta, G. S., Moehle, C. W., Meher, A. K., Su, G., Vigneshwar, N. G., . . . Ailawadi, G. (2013). Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms. FASEB JOURNAL, 27(6), 2122-2131. doi:10.1096/fj.12-214197

Gomez, D., Shankman, L. S., Nguyen, A. T., & Owens, G. K. (2013). Detection of histone modifications at specific gene loci in single cells in histological sections. NATURE METHODS, 10(2), 171-177. doi:10.1038/NMETH.2332

Johnston, W. F., Salmon, M., Su, G., Lu, G., Stone, M. L., Zhao, Y., . . . Ailawadi, G. (2013). Genetic and Pharmacologic Disruption of Interleukin-1β Signaling Inhibits Experimental Aortic Aneurysm Formation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 33(2), 294-+. doi:10.1161/ATVBAHA.112.300432

Starke, R. M., Ali, M. S., Jabbour, P. M., Tjoumakaris, S. I., Gonzalez, F., Hasan, D. M., . . . Dumont, A. S. (2013). Cigarette Smoke Modulates Vascular Smooth Muscle Phenotype: Implications for Carotid and Cerebrovascular Disease. PLOS ONE, 8(8). doi:10.1371/journal.pone.0071954

2012

Leeper, N. J., Raiesdana, A., Kojima, Y., Kundu, R. K., Cheng, H., Maegdefessel, L., . . . Quertermous, T. (2013). Loss of CDKN2B Promotes p53-Dependent Smooth Muscle Cell Apoptosis and Aneurysm Formation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 33(1), E1-+. doi:10.1161/ATVBAHA.112.300399

Nguyen, A. T., Gomez, D., Bell, R. D., Campbell, J. H., Clowes, A. W., Gabbiani, G., . . . Owens, G. K. (2013). Smooth Muscle Cell Plasticity Fact or Fiction?. CIRCULATION RESEARCH, 112(1), 17-22. doi:10.1161/CIRCRESAHA.112.281048

Salmon, M., Gomez, D., Greene, E., Shankman, L., & Owens, G. K. (2012). Cooperative Binding of KLF4, pELK-1, and HDAC2 to a G/C Repressor Element in the SM22α Promoter Mediates Transcriptional Silencing During SMC Phenotypic Switching In Vivo. CIRCULATION RESEARCH, 111(6), 685-+. doi:10.1161/CIRCRESAHA.112.269811

Gomez, D., & Owens, G. K. (2012). Smooth muscle cell phenotypic switching in atherosclerosis. CARDIOVASCULAR RESEARCH, 95(2), 156-164. doi:10.1093/cvr/cvs115

Alexander, M. R., Murgai, M., Moehle, C. W., & Owens, G. K. (2012). Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms. PHYSIOLOGICAL GENOMICS, 44(7), 417-429. doi:10.1152/physiolgenomics.00160.2011

2011

Alexander, M. R., Moehle, C. W., Johnson, J. L., Yang, Z., Lee, J. K., Jackson, C. L., & Owens, G. K. (2012). Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice. JOURNAL OF CLINICAL INVESTIGATION, 122(1), 70-79. doi:10.1172/JCI43713

Moehle, C. W., Bhamidipati, C. M., Alexander, M. R., Mehta, G. S., Irvine, J. N., Salmon, M., . . . Ailawadi, G. (2011). Bone marrow-derived MCP1 required for experimental aortic aneurysm formation and smooth muscle phenotypic modulation. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 142(6), 1567-1574. doi:10.1016/j.jtcvs.2011.07.053

Alexander, M. R., & Owens, G. K. (2012). Epigenetic Control of Smooth Muscle Cell Differentiation and Phenotypic Switching in Vascular Development and Disease. ANNUAL REVIEW OF PHYSIOLOGY, VOL 74, 74, 13-40. doi:10.1146/annurev-physiol-012110-142315

Gan, Q., Thiebaud, P., Theze, N., Jin, L., Xu, G., Grant, P., & Owens, G. K. (2011). WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(24), 21853-21864. doi:10.1074/jbc.M111.233098

Hoofnagle, M. H., Neppl, R. L., Berzin, E. L., Pipes, G. C. T., Olson, E. N., Wamhoff, B. W., . . . Owens, G. K. (2011). Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 300(5), H1707-H1721. doi:10.1152/ajpheart.01192.2010

2010

Dioufa, N., Schally, A. V., Chatzistamou, I., Moustou, E., Block, N. L., Owens, G. K., . . . Kiaris, H. (2010). Acceleration of wound healing by growth hormone-releasing hormone and its agonists. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(43), 18611-18615. doi:10.1073/pnas.1013942107

Jin, L., Gan, Q., Zieba, B. J., Goicoechea, S. M., Owens, G. K., Otey, C. A., & Somlyo, A. V. (2010). The Actin Associated Protein Palladin Is Important for the Early Smooth Muscle Cell Differentiation. PLOS ONE, 5(9). doi:10.1371/journal.pone.0012823

Yoshida, T., Gan, Q., Franke, A. S., Ho, R., Zhang, J., Chen, Y. E., . . . Owens, G. K. (2010). Smooth and Cardiac Muscle-selective Knock-out of Kruppel-like Factor 4 Causes Postnatal Death and Growth Retardation. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(27), 21175-21184. doi:10.1074/jbc.M110.112482