Grant: Operating Grant

The exact role of heme oxygenase-2 is not known although results obtained from genetic models suggest that under or over-activity of this enzyme may be involved in a number of diseases. Potentially, heme oxygenase-2 could be involved in range of human conditions that affect Canadians; these include chronic pain (arguably the costliest disease in developed countries), endometriosis (which affects ~10% of women of child bearing age), blindness due to diabetes and some dementias (Alzheimer Disease). One reason for our lack of understanding of the function of heme oxygenase-2 is the lack of pharmacological tools (drugs) that can be used to study it; we are poised to fill this void. Thus, we have identified drug "hits" as inhibitors and activators of heme oxygenase-2. We propose to exploits these hits as the basis of designing new and better drugs that can be used to study heme oxygenase-2 by using the breadth of expertise possessed by our research team; this includes- medicinal chemistry, x-ray crystallography, computer-assisted drug design, pharmacological testing. We plan to lay the ground work for the full exploitation of heme oxygenase inhibitor and activator drugs by ensuring that they function in the full range of research models used in drug development.