B.Sc. (Liverpool), M.Sc. (Alberta), Ph.D. (B.C.).
A. Calpain protease activation and myocardial ischemia/reperfusion injury.
B. Identification and purification of nuclear calcium-binding proteins
The current research interests are directed towards understanding the biological role of an intracellular protease known as calpain. Calpain is unique amongst endopeptidases in that it acts as a "biotransformer" rather than performing "housekeeping" duties. Enzyme substrates, for example, are mostly activated rather than degraded and the functions of many other proteins are altered rather than destroyed.
Because of these characteristics and the facts that (a) calpain is activated by calcium ions at physiological pH and (b) cleavage sites are between functional domains rather than within, calpain is now recognized as an important mediator of intracellular calcium signalling. The controlled activation of calpain appears to be central to a variety of intracellular processes including cyto/karyoskeletal remodelling, mitosis, platelet activation and the expression of transcriptional factor activity.
In this capacity calpain can be thought of as a "molecular monkeywrench". However, in some nerve and muscle pathologies the activation of calpain is uncontrolled due to intracellular calcium overload and results in impaired intracellular structure and function. If we can inhibit this uncontrolled calpain activity we may be able to minimize cell injury.
A principal hypothesis in our work, therefore, is that calpain-specific inhibitors will be useful in arresting tissue necrosis associated with myocardial infarct. This will be the focus of our work in the next 3 to 5 years
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- J.S.C. Gilchrist, G.N. Pierce. Isolation and characterization of a Calcium binding protein in the nuclear membrane. J. Biol. Chem. 268 (6), 4291-4299, 1993
- Ramjiawan, B., Czubryt, M., Gilchrist, J.S.C., Pierce, G.N. Nuclear membrane cholesterol can modulate nuclear nucleoside triphosphatase activity. J. Cell. Biochem., 63 (4) 442-52, 1996
- Abrenica, B. and Gilchrist, J.S.C. Nucleoplasmic calcium loading regulated by mobilization of perinuclear calcium. Cell Calcium 28(2); 127-36, 2000
- Gilchrist, J.S.C., Abrenica, B., DiMario, P., Czubryt, M., Pierce, G. Nucleolin is a Ca2+-binding protein. J. Cell. Biochem. 85: 268-78, 2002.
- Abrenica, B., Pierce, G.N. and Gilchrist, J.S.C. Nucleoplasmic Calcium regulation in Aortic Vascular Smooth Muscle Cells. Can. J. Physiol. Pharmacol. 81(3): 301-310, 2003
- Gilchrist, J.S.C., Palahniuk, C., Abrenica, B., Rampersad, P., Mutawe, M., and Cook, T. RyR1/SERCA1 Cross-Talk Regulation of Calcium Transport in Heavy Sarcoplasmic Reticulum Vesicles . Can. J. Physiol. Pharmacol. 81(2): 220-233, 2003
- Ander, B.P., Weber, A.R., Rampersad, P., Gilchrist, J.S.C., Pierce, G.N., Lukas, A. Dietary Flaxseed Protects Against Ventricular Fibrillation Induced by Ischemia- Reperfusion in Normal and Hypercholesterolemic Rabbits. The Journal of Nutrition (2004, in press)