Finding Your Way

Bend

Jack Bend

Distinguished University Professor

MSc University of Manitoba
PhD Sydney University, N.S.W., Australia

Office: Siebens Drake Research Institute, Room 107C
1400 Western Road, London ON N6G 2V4
Phone: (519) 850-2456
Fax: (519) 661-3370

Research Interests

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.

Selected Publications

  1. Koren, G. and Bend, J.R.: Fish consumption in pregnancy and fetal risks of methylmercury. Canadian Family Physician, Manuscript ID 2010-04-CFP-0132; In press.
  2. Schoeman, K., Bend, J.R. and Koren, G. Hair methylmercury: A new indication for therapeutic monitoring. Ther. Drug Monit. 32: 289-93, 2010.
  3. Schoeman, K., Tanaka, T., Bend, J.R. and Koren, G. Hair mercury levels of women of reproductive age in Ontario, Canada: Implication to fetal safety and fish consumption. J Pediatr. 157: 127-31, 2010.
  4. Oakes, G.H. and Bend, J.R.: Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J. Biochem. Mol. Toxicol. 24: 73-88, 2010.
  5. Bend, J.R. Invited Speaker, 6th Canadian Oxidative Stress Conference, May 7-10, 2009, Winnipeg, MA. Topic: Micromolar unconjugated bilirubin causes oxidation of the disulfide proteome, apoptosis via mitochondrial signaling and upregulation of several genes involved in ER stress.
  6. Distinguished University Professorship Lecture, University of Western Ontario, April 29, 2009. “Some contributions to molecular, clinical and environmental toxicology”
  7. Elzagallaai, A.A., Knowles, S.P., Rieder, M.J., Bend, J.R., Shear, N.H. and Koren, G.: Systematic review of different in vivo and in vitro tests used for the diagnosis of anticonvulsant hypersensitivity syndrome (AHS): I-Patch Test. Drug Safety 32: 1-18, 2009.
  8. Herbert, C.P., (Presenting Author); Walpole Island First Nation Heritage Centre Team: Jacobs, D., White, D., Williams, N.C., Williams, R., UWO Ecosystem Health Research Team: Bend, J.R., Corbett, B., Darnell, R., Herbert, C.P., Hill, J., Koren, G., Rieder, M.J., Schoeman, K., Stephens, C.V., Trick, C.G., Van Uum, S. "Health Risk of the Walpole Island First Nation Community from Exposure to Environmental Contaminants: a Community-Based Participatory Research Partnership", 2009 Aboriginal Policy Research Conference, Ottawa, Ontario, March 9, 2009  (online paper),

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