Timothy E. O'Toole, Ph.D.

Associate Professor of Medicine
Core Director, Flow Cytometry

502-852-5886 E-mail

Education and Training

Ph.D.: University of Michigan, Biological Chemistry
Postdoctoral Fellowship: Scripps Research Institute

Research Interests

The goal of studies in Dr. O'Toole's lab is to develop a mechanistic understanding whereby environmental exposure adversely impact cardiovascular function. Prior work from this lab characterized the cardiovascular and immune responses of exposure to fine air-borne particulate matter (PM2.5). In humans, exposure to PM2.5 resulted in endothelial damage, deficits of circulating angiogenic cells (CACs), changes in immune cell populations, changes in plasma cytokines, and increased thrombogenicity. In animal models, exposure to concentrated ambient particles induced quantitative and qualitative defects in CACs and platelet activation. Some of these outcomes in mice were mitigated when means were taken to limit oxidative stress. Current efforts seek to identify additional, adverse outcomes in response PM2.5 exposure, the molecular basis of these outcomes, and effective strategies to limit these outcomes. A study characterizing the efficacy and feasibility of carnosine (a naturally occurring β-alanyl-L-histidine dipeptide) supplementation in mitigating adverse outcomes in humans is currently ongoing. In addition to particulate air pollution, Dr. O'Toole's laboratory is also examining the cardiovascular consequences of exposure to volatile organic compounds. Mice exposed to benzene develop insulin resistance while mice exposed to either acrolein or benzene also have CAC deficits. Mechanistic studies to better understand these outcomes of VOC exposure are underway.

Featured Publications

Find all papers and citations via ResearchGate

  • Zhao J, Gomes D, Jin L, Mathis SP, Li X, Rouchka EC, Bodduluri H, Conklin DJ, O'Toole TE. Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice. Ecotoxicol Environ Saf. 2022 Mar 1;232:113239. doi: 10.1016/j.ecoenv.2022.113239. Epub 2022 Jan 29. PMID: 35093814; PMCID: PMC8860873.
  • Malovichko MV, Abplanalp WT, McFall SA, Taylor BS, Wickramasinghe NS, Sithu ID, Zelko IN, Uchida S, Hill BG, Sutaria SR, Nantz MH, Bhatnagar A, Conklin DJ, O'Toole TE, Srivastava S. Subclinical markers of cardiovascular toxicity of benzene inhalation in mice. Toxicol Appl Pharmacol. 2021 Nov 15;431:115742. doi: 10.1016/j.taap.2021.115742. Epub 2021 Oct 5. PMID: 34624356; PMCID: PMC8647905.
  • Haberzettl P, Jin L, Riggs DW, Zhao J, O'Toole TE, Conklin DJ. Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction. Physiol Rep. 2021 Aug;9(15):e14980. doi: 10.14814/phy2.14980. PMID: 34327871; PMCID: PMC8322754.
  • Li X, Haberzettl P, Conklin DJ, Bhatnagar A, Rouchka EC, Zhang M, O'Toole TE. Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice. Genes (Basel). 2021 Jul 10;12(7):1058. doi: 10.3390/genes12071058. PMID: 34356074; PMCID: PMC8307414.
  • Singh P, O'Toole TE, Conklin DJ, Hill BG, Haberzettl P. Endothelial progenitor cells as critical mediators of environmental air pollution-induced cardiovascular toxicity. Am J Physiol Heart Circ Physiol. 2021 Apr 1;320(4):H1440-H1455. doi: 10.1152/ajpheart.00804.2020. Epub 2021 Feb 19. PMID: 33606580; PMCID: PMC8260385.
  • O'Toole TE, Li X, Riggs DW, Hoetker DJ, Baba SP, Bhatnagar A. Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk. Int J Mol Sci. 2021 Jan 30;22(3):1383. doi: 10.3390/ijms22031383. PMID: 33573153; PMCID: PMC7866516.
  • O'Toole TE, Amraotkar AA, DeFilippis AP, Rai SN, Keith RJ, Baba SP, Lorkiewicz P, Crandell CE, Pariser GL, Wingard CJ, Pope Iii CA, Bhatnagar A. Protocol to assess the efficacy of carnosine supplementation in mitigating the adverse cardiovascular responses to particulate matter (PM) exposure: the Nucleophilic Defense Against PM Toxicity (NEAT) trial. BMJ Open. 2020 Dec 28;10(12):e039118. doi: 10.1136/bmjopen-2020-039118. PMID: 33372072; PMCID: PMC7772308.
  • O'Toole TE, Li X, Riggs DW, Hoetker DJ, Yeager R, Lorkiewicz P, Baba SP, Cooper NGF, Bhatnagar A. Urinary levels of the acrolein conjugates of carnosine are associated with inhaled toxicants. Inhal Toxicol. 2020 Nov-Dec;32(13-14):468-476. doi: 10.1080/08958378.2020.1845257. Epub 2020 Nov 12. PMID: 33179563; PMCID: PMC7875462.
  • Li X, Cooper NGF, O'Toole TE, Rouchka EC. Choice of library size normalization and statistical methods for differential gene expression analysis in balanced two-group comparisons for RNA-seq studies. BMC Genomics. 2020 Jan 28;21(1):75. doi: 10.1186/s12864-020-6502-7. PMID: 31992223; PMCID: PMC6986029.
  • Riggs DW, Zafar N, Krishnasamy S, Yeager R, Rai SN, Bhatnagar A, O'Toole TE. Exposure to airborne fine particulate matter is associated with impaired endothelial function and biomarkers of oxidative stress and inflammation. Environ Res. 2020 Jan;180:108890. doi: 10.1016/j.envres.2019.108890. Epub 2019 Nov 5. PMID: 31718786; PMCID: PMC6899204.