Winn | Biomedical and Molecular Sciences | School of Medicine

Louise M. Winn PhD

Position(s)

Professor

Contact Info

winnl@queensu.ca

Botterell Hall Room 557

613-533-6465

Faculty Bio

Ph.D. (1999) - University of Toronto, Collaborative Program in Toxicology and Faculty of Pharmacy

M.Sc. (1995) - University of Toronto, Faculty of Pharmacy

B.Sc. (1990) - University of Minnesota, Biochemistry

My research focuses on the evidence suggesting that fetal toxicity may be mediated, at least in part, by the embryonic bioactivation of xenobiotics (i.e. pharmaceutical drugs and environmental chemicals) to free radical intermediates, which can lead to increased oxidative stress and ultimately teratogenesis. I am particularly interested in the effects of increased oxidative stress on embryonic signalling pathways and embryonic homologous DNA recombination. Currently my lab is focusing on several xenobiotics including benzene, flame retardants and valproic acid as models of xenobiotic-initiated teratogenesis. Using both in vivo animal and cell culture models, we are evaluating the effects of these xenobiotics on embryonic signalling pathways involving several proteins including c-Myb, Pim-1, Ras and p300/CBP. Additionally, we are investigating mechanisms of xenobiotic-initiated homologous recombination and the role of oxidative stress in this process. Examples of the kinds of studies that my lab is interested in include: the evaluation of the molecular biological effects of in utero xenobiotic exposure on the offspring of exposed female mice, including alterations in cell signalling pathways; the evaluation of xenobiotic-initiated ROS production and embryonic oxidative damage; and the effects of xenobiotic exposure on homologous DNA recombination

Research Interests

My research focuses on the evidence suggesting that fetal toxicity may be mediated, at least in part, by the embryonic bioactivation of xenobiotics (i.e. pharmaceutical drugs and environmental chemicals) to free radical intermediates, which can lead to increased oxidative stress and ultimately teratogenesis. I am particularly interested in the effects of increased oxidative stress on embryonic signalling pathways and embryonic homologous DNA recombination. Currently my lab is focusing on several xenobiotics including benzene, flame retardants, and valproic acid as models of xenobiotic-initiated teratogenesis. Using both in vivo animal and cell culture models, we are evaluating the effects of these xenobiotics on embryonic signalling pathways involving several proteins including c-Myb, Pim-1, Ras and p300/CBP. Additionally, we are investigating mechanisms of xenobiotic-initiated homologous recombination and the role of oxidative stress in this process. Examples of the kinds of studies that my lab is interested in include: the evaluation of the molecular biological effects of in utero xenobiotic exposure on the offspring of exposed female mice, including alterations in cell signalling pathways; the evaluation of xenobiotic-initiated ROS production and embryonic oxidative damage; and the effects of xenobiotic exposure on homologous DNA recombination and other DNA repair mechanisms.

Selected Publications

Philbrook, N.A. and Winn, L.M. (2015) Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice. Toxicol. Appl. Pharmacol. (accepted)
Philbrook, N.A. and Winn, L.M. (2015) Benzoquinone-mediated increased DNA damage and decreased Ogg1 gene expression are not altered by sulforaphane pretreatment in cultured CD-1 mouse fetal liver cells. (submitted)
Lamparter, C and Winn, L.M. (2014) Tissue-specific effects of valproic acid on DNA repair genes and apoptosis in post-implantation mouse embryos. Toxicol. Sci. 141: 59-67.
Tung, E.W.Y., Philbrook, N.A., Belanger, C.L., Ansari, A. and Winn, L.M. (2014) Benzo[a]pyrene increases DNA double strand break repair in vitro and in vivo: a possible mechanism for benzo[a]pyrene-induced toxicity. Mutation Research – Genetic Toxicology and Environmental Mutagenesis 760: 64-69.
Stokes, S.E. and Winn, L.M. (2014) NK-kB signaling is increased in HD3 cells following exposure to 1,4-benzoquinone: Role of reactive oxygen species and p38-MAPKa. Toxicol. Sci. 137: 303-310.
Philbrook, N.A. and Winn, L.M. (2014) Sub-chronic sulforaphane exposure in CD-1 pregnant mice enhances maternal NADPH quinone oxidoreductase 1 (NQO1) activity and mRNA expression of NQO1, glutathione S-transferase, and glutamate-cysteine ligase: Potential implications for fetal protection against toxicant exposure. Repro. Toxicol. 43: 30-37.
Tung, E. Y.Y., Philbrook, N.A , MacDonald, K.D.D. and Winn, L.M. (2012) DNA double strand breaks and DNA recombination in benzene-metabolite induced genotoxicity. Toxicol. Sci. 126: 569-577.
Philbrook, N.A., Walker, V.K., Afrooz, A.R.M.N, Saleh, N.V. and Winn, L.M. (2011) Investigating the effects of functionalized carbon nanotubes on reproduction and development in Drosophila melanogaster and CD-1 mice. Repro. Toxicol. 32: 442-448.
Philbrook, N.A., Winn, L.M., Afrooz, A.R.M.N, Saleh, N.V. and Walker, V.K. (2011) The effect of TiO2 and Ag nanoparticles on reproduction and development of Drosophila melanogaster and CD-1 mice. Toxicol. Appl. Pharmacol. 257: 429-436.
Tung, E. Y.Y. and Winn, L.M. (2011) Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: A role for oxidative stress in valproic acid-induced neural tube defects. Mol. Pharmacol. 80: 979-987.
Tung, E. Y.Y. and Winn, L.M. (2011) Valproic acid induced DNA damage increases embryonic p27KIP1 and caspase-3 expression: A mechanism for valproic acid-induced neural tube defects. Repro. Toxicol. 32:255-260.