Timothy O’Toole Lab

About

My lab uses a variety of cellular and molecular approaches, and both human and animal models, to study how environmental exposures promote cardiovascular disease. Previously, we determined that murine exposure to fine airborne particulate matter (PM2.5) induced vascular dysfunction, altered the abundance and functionality of endothelial progenitor cells, promoted inflammatory responses, and induced defects in hematopoiesis and insulin signaling. In subsequent studies, we determined that means taken to limit oxidative stress can mitigate these adverse outcomes and we have recently completed a randomized human clinical trial examining the efficacy of carnosine supplementation in doing the same. Related, we have also examined the effects of inhalation exposure to acrolein and benzene in mice. As with PM2.5, exposure to these two volatiles disrupts glucose homeostasis and vascular repair processes. More recent studies have focused on the potential toxicity of environmental microplastics (MP) exposure. In mouse studies, we determined that oral polystyrene consumption promotes adiposity, hyperglycemia, and elevated HOMA IR scores, and potentiates atherosclerotic lesion size in disease-prone strains as well. Ongoing efforts seek to further evaluate the outcomes of PM2.5 and MP exposure, the mechanistic basis for these effects, and the identification of practical interventional approaches.

Team

Timothy O’Toole Ph.D., Associate Professor and Lab PI, tim.otoole@louisville.edu
Jingjing Zhao Ph.D., Research Associate, jingjing.zhao@louisville.edu
Daniel Gomes M.S., Department of Pharmacology and Toxicology Ph.D. candidate, daniel.gomes@louisville.edu

Our Work

Exposure to microplastics and impacts on health
PM2.5 exposure and cellular aging
Health-promoting effects of carnosine supplementation

Impacts of polystyrene, polyethylene, and polyvinyl chloride on glucose homeostasis, hepatic function, and atherogenesis in mice; defining the cellular mechanisms for these effects; identifying interventional approaches
Impacts of PM2.5 exposure on telomere dynamics, cell growth, and senescence in mice; defining the mechanisms for these effects; identifying interventional approaches
Evaluating how PM2.5 exposure impacts cardiovascular disease risk, cognition, and physical strength in a human cohort; examining how these effects are modified by carnosine

Zhao, J., Gomes, D., Yuan, F., Feng, J., Zhang, X., O’Toole, T.E. Oral polystyrene consumption potentiates atherosclerotic lesion formation in ApoE-/- mice. Circ. Res. 134: 1228-1230, 2024. PMID: 38662862
Baba, S.P., Amraotkar, A.R., Hoetker, D., Gao, H., Gomes, D., Zhao, J., Wempe, M.F., Rice, P.J., DeFilippis, A.P., Rai, S.N., Pope, C.A. III, Bhatnagar, A., O’Toole, T.E. Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial. Amino Acids 56: 55, 2024. PMID: 29215872
Zhao, J., Adiele, N., Gomes, D., Malovichko, M., Conklin, D.J., Ekuban, A., Luo, J., Gripshover, T., Watson, W.H., Banerjee, M., Smith, M.L., Rouchka, E.C., Xu, R., Zhang, X., Gondim, D.D., Cave, M.C., O’Toole, T.E. Obesogenic polystyrene microplastic exposures disrupt the gut-liver-adipose axis. Tox. Sci., 26: 210-220, 2024. PMID: 38291899
Amraotkar, A.R., Hoetker, D., Negahdar, M.J., Ng, C.J., Lorkiewicz, P., Owolabi, U.S., Baba, S.P., Bhatnagar, A., O’Toole, T.E. Comparative evaluation of different modalities for measuring in vivo carnosine levels. PLOS One. 19: e0299872, 2024. PMID:38536838
Zhao, J., Gomes, D., Jin, L., Mathis, S.P., Li, X., Rouchka. E.C., Bodduluri, H., Conklin, D.J., and O’Toole, T.E. Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice. Ecotoxicology and Environmental Safety. 232: 113239. 2022. PMID: 35093814
Li, X., Haberzettl, P., Conklin, D.J., Bhatnagar, A., Rouchka, E.C., Zhang, M., and O’Toole, T.E. Exposure to fine particulate matter air pollution alters mRNA and miRNA expression in bone marrow-derived endothelial progenitor cells from mice. Genes. 12: 1058, 2021. PMID: 34356074
O’Toole, T.E., Li, X., Riggs, D.W., Hoetker, D.J., Baba, S., and Bhatnagar, A. Urinary levels of the acrolein conjugates of carnosine are associated with cardiovascular disease risk. Int. J. Mol. Sci. 22:1383, 2021. PMID: 33573153.
Abplanalp, W., Haberzettl, P., Bhatnagar, A., Conklin, D.J., and O’Toole T.E. Carnosine supplementation mitigates the deleterious effects of particulate matter exposure in mice. Journal of the American Heart Association, 8: e013041, 2019. PMID: 31234700
Abplanalp, W., Wickramasinghe, N.S., Sithu, S.D., Conklin, D.J., Xie, Z., Bhatnagar, A., Srivastava, S., and O’Toole, T.E. Benzene exposure induces insulin resistance in mice. Tox. Sci. 167: 426-437, 2019. PMID: 30346588
Pope, C.A.III, Bhatnagar, A., McCracken, J.P., Abplanalp, W., Conklin, D.J., and O’Toole, T.E. Exposure to fine particulate air pollution is associated with endothelial injury and systemic inflammation. Circ. Res. 119: 1204-1214, 2016. PMID: 27780829