The program presented is focused on understanding the mechanisms of action of kinins, natural substances in the body, as well as synthetic analogues. It also focuses on their potential usefulness in the treatment of cardiovascular diseases, diabetes and brain cancer. This program has three components:
The first, most basic, is interested in the signalling process and the biological roles of kinin receptors in normal physiology and in pathologies. My laboratory and those of my collaborators recently demonstrated the existence of receptors in the nucleus of cells, which bind different hormones including bradykinin. These "nuclear" receptors are capable of modulating expression of some of our genes associated with inflammation. The impact of this "compartmentalization" in the cell nucleus on the biological functions of kinin receptors is central to this component.
The second part relates more specifically to the potential use of kinins to improve the management of diabetes with insulin. Indeed, kinins promote vasodilatation which can lead to better absorption of insulin injected. This project aims to demonstrate the superiority of the clinical effectiveness of insulin when combined with a kinin in obese people with type 2 diabetes. These constitute the majority of patients treated with intensive insulin therapy.
The third part will evaluate kinin analogues as adjunctive therapy to chemotherapy to treat malignant brain tumours. Our preclinical studies have shown that a synthetic agonist of the kinin B1 receptor allowed non-therapeutic molecules of various sizes to reach more easily and selectively brain tumours by increasing the permeability of blood vessels in the brain.
Through this program, we will contribute to the fight against diseases that afflict many Quebecers and Canadians.