Dr. Bradly Wouters
Executive Vice President, Science & Research | University Health Network
Toronto, ON, CA
Dr. Wouters’ lab has identified new signaling pathways that influence how tumours respond to environments with reduced oxygenation
Dr. Bradly G. Wouters is Executive Vice President, Science & Research, and a full professor in the Departments of Radiation Oncology and Medical Biophysics at the University of Toronto. He is cross appointed as an Associate Chair of Graduate Studies and Director of Radiation Biology within the Department of Radiation Oncology as well as Senior Investigator in the Selective Therapy Program at the Ontario Institute for Cancer Research. He has been a faculty member on the European Society for Radiotherapy and Oncology (ESTRO) teaching course on Basic Clinical Radiobiology in Europe for the past 10 years and was also the director of the ESTRO Molecular Oncology for the Radiation Oncologist course for more than 5 years. He has contributed as an author to several of the chapters in the Basic Clinical Radiobiology textbook used in Europe and many other parts of the world. Dr. Wouters is the recipient of several prestigious awards and honors. As well, Dr Wouters was named the recipient of the ESTRO Klaas Breur Award – Annual Gold Medal Award Lecture for 2011. Other notable awards include the Michael Fry Radiation Research Award in 2009 from the Radiation Research Society and the Senior Investigator Award with the Ontario Institute for Cancer Research. Brad is an internationally recognized leader in the field of molecular radiation oncology with a primary interest in understanding the cellular and molecular responses to hypoxia and their influence on the biological behavior of tumours.
Industry Expertise (4)
Areas of Expertise (2)
University of Saskatchewan: BSc, Science
University of British Columbia: MSc, Science
University of British Columbia: PhD, Science
- Professor, Department of Radiation Oncology, University of Toronto
- Professor, Department of Medical Biophysics, University of Toronto
- Academic Program Director, Radiation Biology
- Director, Hypoxia and Microenvironment Program, Ontario Cancer Institute
Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.
Mass cytometry (MC) offers unparalleled potential for the development of highly parameterized assays for characterization of single cells within heterogeneous populations. Current reagents compatible with MC analysis employ antibody-metal-chelating polymer conjugates to report on the presence of biomarkers. Here, we expand the utility of MC by developing the first activity-based probe designed specifically for use with the technology. A compact MC-detectable telluroether is linked to a bioreductively sensitive 2-nitroimidazole scaffold, thereby generating a probe sensitive to cellular hypoxia. The probe exhibits low toxicity and is able to selectively label O2 -deprived cells. A proof-of-concept experiment employing metal-bound DNA intercalators demonstrates that a heterogeneous mixture of cells with differential exposure to O2 can be effectively discriminated by the quantity of tellurium-labeling. The organotellurium reagents described herein provide a general approach to the development of a large toolkit of MC-compatible probes for activity-based profiling of single cells.
Regions of acute and chronic hypoxia exist within solid tumors and can lead to increased rates of mutagenesis and/or altered DNA damage and repair protein expression. Base excision repair (BER) is responsible for resolving small, non-helix-distorting lesions from the genome that potentially cause mutations by mispairing or promoting DNA breaks during replication.
Conditions of poor oxygenation (hypoxia) are present in the majority of solid human tumors and are associated with poor patient prognosis due to both hypoxia-mediated resistance to treatment, and to hypoxia induced biological changes that promote increased malignancy, including metastasis. Tumor cells respond to hypoxia by activating several oxygen-sensitive signaling pathways that include the hypoxia inducible factor 1/2 (HIF1/2) signalling pathways and the unfolded protein response (UPR), which alter gene expression to promote adaptation and survival during hypoxic conditions. Furthermore, these hypoxia responsive pathways can lead to changes in gene expression and cellular phenotype that influence the potential of cancer cells to metastasize. However, the hypoxia-induced signaling events that promote tumor metastasis are still relatively poorly understood. Previous studies have largely focused on the contribution of the HIF signaling pathway to hypoxia-mediated metastasis. However, recent evidence demonstrates that hypoxic activation of the UPR is also an important mediator of metastasis.
The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage.