Peter
Wells
Area of Research
Professor Peter Wells’ research focuses on the body’s adverse reactions to drugs and environmental chemicals, and to forms of activated oxygen in the body, termed reactive oxygen species (ROS), that are essential for life but can cause disease in predisposed people. By investigating the molecular and biochemical pathways of these reactions, Wells is working to explain the genetic and environmental determinants of susceptibility to disease and chemical toxicity. This includes a number of both drug-induced and spontaneous diseases such as cancer, neurodevelopmental disorders and neurodegenerative diseases.
Research Challenge
Drugs and other chemicals that enter the body can be converted into highly reactive intermediates by a process called bioactivation. These toxic compounds can react with proteins, lipids and DNA, to cause disrupted cellular function and even cell death. Even in the absence of chemical exposure, the body naturally converts oxygen to reactive oxygen species (ROS) which, while essential for life, can cause the same adverse effects as drug reactive intermediates. Some drugs also increase the body’s formation of ROS. Luckily, the human body has evolved mechanisms to clear these reactive intermediates, including ROS, and repair the damage they cause. However, some individuals are predisposed to increased production or impaired clearance of these intermediates, or are unable to efficiently repair the damage. These imbalances lead them to experience disease at normally safe doses of a drug, or in the absence of drug exposure, from increased ROS effects.
Proposed Solution
Wells studies the molecular mechanisms and role of drug reactive intermediates and ROS in toxicity and diseases of the brain, both in utero and after birth. Drug-induced toxicity or an improper balance of ROS in the fetus may be the basis for some developmental disorders and fetal death. The Wells group uses a combination of chemical, biochemical, molecular biological and behavioural techniques in the context of in vivo and in vitro experiments including animal models and cell and whole embryo culture.
Impact to date
The Wells group has made numerous contributions to our understanding of toxic mechanisms and genetic determinants of neurodevelopmental and neurodegenerative diseases. They recently discovered that knocking out just a single copy of the breast cancer 1 gene (Brca1), generally known to protect against cancers, can cause abnormal embryonic development and neurodevelopmental disorders after birth in animal models. If a similar effect occurs in humans, changes in this gene and/or its BRCA1 protein could be key to identifying embryos at risk of developmental disorders. This and other knowledge gained from these studies may inform research on the mechanism of related disease factors in humans and clear the path for the development of diagnostic tests and preventative treatments.
Publications
Awards
Scientific Achievement Award, Society of Toxicology (USA), Reproductive and Developmental Toxicology Specialty Section, March 2019.
Awarded for lifetime achievement for a particularly influential body of work in the field of reproductive and developmental toxicology.
Gabriel L Plaa Award of Distinction, Society of Toxicology Canada, December 2018.
To honour those individuals who have made outstanding and sustained contributions to the science of toxicology in Canada and/or the Society of Toxicology of Canada.
2015 Chappel Memorial Lecturer, University of Guelph, Ontario Veterinary College, Guelph, Ontario, April 2015.
Awarded every other year to “an internationally renowned scientist who plays a key leadership role in the biomedical sciences”. Lecture title: “Oxidative stress and DNA damage in the fetal basis of adult disease.”
AFPC-Pfizer Research Career Award, Association of Faculties of Pharmacy of Canada, June 2011.
Awarded for “a distinguished career in pharmaceutical research, and for exerting a broad influence on pharmaceutical research, including the supervision of graduate students and/or postdoctoral fellows, as recognized by peers at national and international levels”.
Keywords: toxicology, drug metabolism, animal models, disease, metabolism, bioactivation, cellular death, pathological sequelae, neurodegenerative disease, cancer, CNS, developmental deficits, drug toxicity
