Professor of Biochemistry and Biomedical Sciences
Atherosclerosis is a major cause of heart disease and stroke, among the leading causes of hospitalization and death in Western countries. It is a multifactorial disease involving a variety of physiological pathways. These include innate immunity, inflammation and lipoprotein metabolism.
Our laboratory utilizes mouse molecular genetics to delineate the contribution of components of these pathways to the development of atherosclerosis. The mouse has been an extremely useful model genetic system to analyze pathways involved in atherosclerosis. In conventional mouse models of atherosclerosis, including the workhorse apoE and LDL receptor knockout mouse strains, atherosclerosis develops primarily in the aorta while coronary arteries, which feed the heart, appear resistant to disease. In contrast, mice that lack a receptor for high density lipoproteins develop extensive atherosclerosis in their coronary arteries as well as increased atherosclerosis in their aortas. These mice develop myocardial infarction as a result of the extensive coronary artery atherosclerosis. This suggests that the HDL receptor, called SR-BI, plays a key role in protection against coronary artery atherosclerosis. One of the main focuses of the lab is to delineate the mechanisms by which expression of SR-BI in bone marrow derived cells including macrophages, protects against atherosclerosis. In particular, we are interested in understanding the role of this receptor in lipid transport as well as cell signalling.
We are also making use of our mouse models of coronary artery atherosclerosis to delineate the factors that normally contribute to the resistance of mouse coronary arteries to atherosclerosis development, as well as to test the contribution of different physiological pathways to the development of coronary artery atherosclerosis and myocardial infarction.