Distinguished University Emeritus Professor
MSc University of Manitoba
PhD Sydney University, Australia
Office: SDRI 107C
Phone: (519) 850.2456 x82456
Keywords: mechanisms of toxicity of endogenous (bilirubin) and exogenous (methylmercury; polycyclic hydrocarbons; persistent organic chemicals or POPs including PCBs, insecticides and dioxins) chemicals; oxidative stress; disulphide proteome; mitochondrial damage; antioxidants of synthetic and natural (e.g. herbal) origin; attenuation of adverse drug reactions
Description of Research Activities: Research in this laboratory is directed towards an understanding of the molecular mechanisms by which endogenous and exogenous (xenobiotic) chemicals cause toxicity, and the mechanisms by which pre-existing pathological conditions such as oxidative stress/infection, dramatically enhance this toxicity. An integrated experimental approach is used so that mechanistic observations elucidated with purified enzymes, subcellular fractions or cell culture are pursued in vivo, an approach facilitated by genomics and proteomics techniques. Special attention is given to chemicals that exert their toxicity through activation of cell signaling networks (e.g. ligands for the aryl hydrocarbon receptor); to electrophilic metabolites of drugs or environmental contaminants which cause toxicity subsequent to covalent reaction with nucleophilic sites on proteins and nucleic acids; and to chemicals (bilirubin; sulfonamides, anti-epileptic drugs: POPs and heavy metals) that exert their toxicity by oxidative and/or nitrosative stress. Studies are performed with compounds that are either of clinical (bilirubin; sulphamethoxazole) or environmental (methylmercury; polycyclic aromatic hydrocarbons; PCBs; heavy metals) significance and include laboratory and clinical studies (in collaboration with Professor Michael Rieder, MD, PhD) and field work (in collaboration with members of the Ecosystem Health Group, Schulich School of Medicine & Dentistry; the Walpole Island First Nation (WIFN) Heritage Centre and Health Centre; and the Attawapiskat First Nation (AttFN)). Current investigations are correlating genomic (gene microarray) and proteomic (protein thiol-glutathione mixed disulphides; protein sulphinic and sulphonic acids) endpoints of bilirubin toxicity with intracellular redox status determined by confocal microscopy with novel, mutated green fluorescence proteins; evaluating the use of compounds of herbal origin to attenuate the adverse drug effects caused by sulphamethoxazole and its electrophilic metabolites; and determining the current exposures of members of the WIFN and AttFN to environmental contaminants for potential correlation with adverse health outcomes such as enhanced risk for type 2 diabetes.