O'Toole, Timothy - University of Louisville - Department of Biochemistry and Molecular Genetics

研究领域

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.

近期论文

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Wheat LA, Haberzettl P, Hellmann J, Baba SP, Bertke M, Lee J, McCracken J, O'Toole TE, Bhatnagar A, Conklin DJ. Acrolein inhalation prevents vascular endothelial growth factor-induced mobilization of Flk-1+/Sca-1+ cells in mice.Arterioscler Thromb Vasc Biol.2011 Jul;31(7):1598-606. doi: 10.1161/ATVBAHA.111.227124. Epub 2011 Apr 28. Haberzettl P, Lee J, Duggineni D, McCracken J, Bolanowski D, O'Toole TE, Bhatnagar A, Conklin DJ. Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow.Environ Health Perspect.2012 Jun;120(6):848-56. doi: 10.1289/ehp.1104206. Epub 2012 Mar 14. 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. 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. Sithu SD, Srivastava S, Siddiqui MA, Vladykovskaya E, Riggs DW, Conklin DJ, Haberzettl P, O'Toole TE,Bhatnagar A, D'Souza SE. Exposure to acrolein by inhalation causes platelet activation.Toxicol Appl Pharmacol. 2010 Oct 15;248(2):100-10. doi: 10.1016/j.taap.2010.07.013. Epub 2010 Aug 3. 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. Podolnikova NP, O'Toole TE, Haas TA, Lam SC, Fox JE, Ugarova TP. Adhesion-induced unclasping of cytoplasmic tails of integrin alpha(IIb)beta3.Biochemistry. 2009 Jan 27;48(3):617-29. doi: 10.1021/bi801751s. Buensuceso CS, Woodside D, Huff JL, Plopper GE, O'Toole TE.The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration.J Cell Sci. 2001 May;114(Pt 9):1691-8. O'Toole TE, Ylanne J, Culley BM. Regulation of integrin affinity states through an NPXY motif in the beta subunit cytoplasmic domain.J Biol Chem. 1995 Apr 14;270(15):8553-8.