Timothy O'Toole, Ph.D.

Assistant Professor of Medicine

Department of Medicine, Division of Cardiovascular Medicine

502-852-5886 tim.otoole@louisville.edu

Research Interests:

Dr. O'Toole's research interests focus on the function and regulation of the endothelium in various disease states. The endothelial progenitor cells (EPCs) are a bone marrow-derived stem cell type that participate in neo-vascularization and wound repair. Upon ischemic insult or other vascular injury, these cells are mobilized from the bone marrow and home to the site of injury. The importance of these cells for vascular health has been suggested in several studies, which suggest that levels of these cells are inversely correlated with risk factors for cardiovascular disease. Accordingly, in preliminary studies it has been demonstrated that there is a mobilization defect of EPCs in murine models of diabetes and in humans or mice exposed to certain environmental pollutants. The efforts in Dr. O’Toole’s laboratory seek to better characterize these observations, understand their molecular basis, and seek therapeutic means to alleviate this defect. In other studies, Dr. O’Toole is interested in the role of miRNA in endothelial regulation. These ubiquitously expressed small RNA species are important regulators of protein expression. The cellular repertoire of miRNAs at any given time is influenced by differentiation state, growth properties, and external signals among others factors. Thus Dr. O’Toole is interested in understanding how diabetic conditions and pollutant exposure affects endothelial miRNA content and the consequent changes in protein expression levels and cellular function.

Selected Publications:

  • Haberzettl P, Conklin DJ, Abplanalp WT, Bhatnagar A, O'Toole TE. Inhalation of Fine Particulate Matter Impairs Endothelial Progenitor Cell Function Via Pulmonary Oxidative Stress. Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):131-142. doi: 10.1161/ATVBAHA.117.309971. Epub 2017 Nov 30. PubMed PMID: 29191925; PubMed Central PMCID: PMC5746456.
  • Abplanalp W, DeJarnett N, Riggs DW, Conklin DJ, McCracken JP, Srivastava S, Xie Z, Rai S, Bhatnagar A, O'Toole TE. Benzene exposure is associated with cardiovascular disease risk. PLoS One. 2017 Sep 8;12(9):e0183602. doi: 10.1371/journal.pone.0183602. eCollection 2017. PubMed PMID: 28886060; PubMed Central PMCID: PMC5590846.
  • Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress. Environ Health Perspect. 2016 Dec;124(12):1830-1839. Epub 2016 Apr 29. PubMed PMID: 27128347; PubMed Central PMCID: PMC5132639.
  • Abplanalp WT, Conklin DJ, Cantor JM, Ginsberg MH, Wysoczynski M, Bhatnagar A, O'Toole TE. Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes. Diabetes. 2016 Nov;65(11):3505-3515. Epub 2016 Aug 5. PubMed PMID: 27495221; PubMed Central PMCID: PMC5079633.
  • Pope CA 3rd, Bhatnagar A, McCracken JP, Abplanalp W, Conklin DJ, O'Toole T. Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation. Circ Res. 2016 Nov 11;119(11):1204-1214. doi: 10.1161/CIRCRESAHA.116.309279. Epub 2016 Oct 25. PubMed PMID: 27780829; PubMed Central PMCID: PMC5215745.
  • DeJarnett N, Yeager R, Conklin DJ, Lee J, O'Toole TE, McCracken J, Abplanalp W, Srivastava S, Riggs DW, Hamzeh I, Wagner S, Chugh A, DeFilippis A, Ciszewski T, Wyatt B, Becher C, Higdon D, Ramos KS, Tollerud DJ, Myers JA, Rai SN, Shah J, Zafar N, Krishnasamy SS, Prabhu SD, Bhatnagar A. Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells. Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2468-77. doi: 10.1161/ATVBAHA.115.305724. Epub 2015 Aug 20. PubMed PMID: 26293462; PubMed Central PMCID: PMC4862408.
  • O'Toole TE, Abplanalp W, Li X, Cooper N, Conklin DJ, Haberzettl P, Bhatnagar A. Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a. Toxicol Sci. 2014 Aug 1;140(2):271-82. doi: 10.1093/toxsci/kfu087. Epub 2014 May 8. PubMed PMID: 24812010; PubMed Central PMCID: PMC4176051.
  • O'Toole TE, Bialkowska K, Li X, Fox JE. Tiam1 is recruited to β1-integrin complexes by 14-3-3ζ where it mediates integrin-induced Rac1 activation and motility. J Cell Physiol. 2011 Nov;226(11):2965-78. doi: 10.1002/jcp.22644. PubMed PMID: 21302295.
  • O'Toole TE, Hellmann J, Wheat L, Haberzettl P, Lee J, Conklin DJ, Bhatnagar A, Pope CA 3rd. Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells. Circ Res. 2010 Jul 23;107(2):200-3. doi: 10.1161/CIRCRESAHA.110.222679. Epub 2010 Jul 1. PubMed PMID: 20595651; PubMed Central PMCID: PMC2943671.
  • O'Toole TE, Zheng YT, Hellmann J, Conklin DJ, Barski O, Bhatnagar A. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages. Toxicol Appl Pharmacol. 2009 Apr 15;236(2):194-201. doi: 10.1016/j.taap.2009.01.024. Epub 2009 Feb 7. PubMed PMID: 19371603; PubMed Central PMCID: PMC2677519.