Education and Professional Standing
PhD, University College London (UK), 1968
BSc, McMaster University, 1964
Chronic inflammation and tissue remodeling
For a number of years our group has been interested in the molecular events that control the complex process of chronic inflammation. Acute events resulting in the initiation of the inflammatory response are in the most protective and lead to normal tissue repair and return to normal function. We have been studying the molecular controls that govern the conversion of acute responses to chronic inflammatory responses. The chronic nature of the response results in on-going repair and tissue remodeling, with altered cell and matrix deposition and compromise to tissue function. Such is the case in fibrosis, with common mechanisms and mediators in pulmonary, hepatic and dermal fibrosis, as well as joint remodeling.
We use gene transfer technologies to determine the role(s) of individual cytokine genes to the process of fibrogenesis and have shown that over-expression of active TGF 1 in a tissue- or organ-restricted manner leads to chronic fibrogenesis that involves, but is restricted to, the entire organ of expression. TGF 1 delivered to the lung induces progressive pulmonary fibrosis and represents an ideal model of this disease for therapeutic drug discovery. We also use drug- (bleomycin) and radiation-induced models to test the concepts of gene therapy in fibrosis using genes encoding natural inhibitors of TGF. Using a similar approach we are investigating the involvement of fibrogenesis in peritoneal dialysis membrane failure and uses of gene therapy for intervention.
Cytokine gene transfer and models of inflammation will be developed to identify new targets for therapeutic drug discovery through gene array assessments.
See selected publications here
See team members here