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Researcher, Children’s Hospital Research Institute of Manitoba; Professor & Head, Department of Pharmacology and Therapeutics, University of Manitoba.
Adenosine receptor signalling plays an important role in a wide range of neurological conditions, including epilepsy, stroke, Parkinson’s Disease, and has been suggested to be important in psychiatric conditions such as psychosis and depression. Two of the world’s most popular drugs, caffeine and ethanol, owe some (ethanol) or all (caffeine) of their effects to altering adenosine receptor activity; this further underlines the importance and relevance of our studies.
Adenosine is an important inhibitory neuromodulator in the brain. Its concentration is controlled by purine enzymes as well as by cellular transport processes (nucleoside transporters) that carry adenosine across cell membranes. ATP is also an important signalling molecule, in addition to its role as an energy molecule. Both ATP receptors (termed purinergic; P2) and adenosine receptors are located on cell surfaces, so the extracellular concentrations of ATP and adenosine determine their level of activity. Adenosine can be formed from ATP both inside and outside cells. Understanding where adenosine comes from (e.g. which cell types, enzymes, transporters), and how it can be produced so rapidly during ischemic events, are major focuses of my research.
Many drugs, including caffeine and ethanol, act at least in part through effects of adenosine receptor signalling. Another focus of my research is investigating the mechanisms of action of these drugs, and others, that affect adenosine signalling.
Using a wide range of techniques, from molecular to behaviour, my laboratory is investigating the cellular sources of neuroactive adenosine and mechanisms by which drugs or diseases enhance adenosine receptor signalling.
Current funding for this research is from Natural Sciences and Engineering Research Council, the Canadian Institutes of Health Research and the University of Manitoba.