Cardiovascular Pharmacology & Drug Design
While my present research has its roots in cardiovascular pharmacology, it now applies also to other areas of pharmacology, including cancer and CNS. My research interests lie in the pharmacology of carbon monoxide (CO) and heme oxygenase (HO), and how CO as well as inhibitors and activators of HO can be developed for human use. This has evolved from earlier research on the pharmacology of organic nitrate vasodilators (nitroglycerin, glyceryl trinitrate) and nitric oxide (NO). HO catabolizes heme to liberate CO, biliverdin and iron, one of the questions that we addressed previously was the importance of the availability of heme for HO as well as other heme-requiring enzymes in the context of hypertension.
In our earlier work on CO and other gasotransmitters, the requirement for better pharmacological tools to study the HO system became a progress-limiting impediment. This led to our present research, which focuses on the creation and application of novel inhibitors of HO, both HO-1 and HO-2, and activators of HO-1 and HO-2. Some of our new compounds have been observed to be selective for inhibition of the inducible isoform, HO-1, and others show selectivity for the constitutive isoform, HO-2. These second generation HO inhibitors are being investigated for their application to various disease states for which current pharmacological treatment requires significant improvement. In parallel with our work on HO inhibitors, we have identified drugs that selectively activate HO-2, and others that activate both HO-1 and HO-2.
This work is done in collaboration with Drs. James Brien, Zhongchao Jia & Bruce Elliott, School of Medicine; Dr. Walter Szarek, Department of Chemistry; off campus private sector companies. Other members of the research team are: Maaike Hum, Brian McLaughlin, and Drs. Mona Rahman and Dragic Vukomanovic.
I am also participating in clinical research projects that involve CO and HO; the principal investigators for these projects are Drs. Paul Belliveau & Darrin Payne, Surgery.
We are grateful to Canadian taxpayers for their support through the Canadian Institutes of Health Research; we also recognize donors to the Heart & Stroke Foundation of Ontario for their support of many earlier publications.