We study the mechanisms of formation of high density lipoproteins (HDL) in order to develop novel therapies to increase HDL for the treatment and prevention of ischemic vascular disease.
HDL, lipoproteins, cholesterol metabolism, cardiovascular risk factors, prevention of cardiovascular disease and diabetes
The Francis laboratory studies the mechanisms of formation of high density lipoproteins (HDL), in order to develop novel methods of increasing HDL production in the body for the prevention of ischemic cardiovascular disease. A major focus is the regulation of the key protein needed to produce new HDL, the ATP-binding cassette transporter A1 (ABCA1), using cellular and animal models. Our current projects are focused on: 1) our demonstration, using cells from humans with the lysosomal cholesterol storage disorders Niemann-Pick Disease type C and Cholesteryl Ester Storage Disease, that cholesterol coming specifically out of lysosomes is a key regulator of ABCA1 gene expression; 2) the demonstration that proteins in a modified form of HDL, tyrosyl radical-oxidized HDL, have the unique ability to stabilize ABCA1 against degradation, suggesting peptides based on the structure of these proteins may be useful to enhance ABCA1 activity therapeutically; and 3) our previous finding that ABCA1 expression is low in atherosclerotic plaque smooth muscle cells. This provides a new explanation for the over accumulation of cholesterol in plaques leading to heart attacks and strokes, and a novel target to reduce this accumulation for the prevention of these diseases. Dr. Francis is also Director of the Healthy Heart Program Prevention (previously Lipid) Clinic at St. Paul’s Hospital, and directs multiple clinical projects into effective treatments for the prevention of cardiovascular disease and diabetes.
Non-work interests include being the father of three children, cycling (GranFondo), swimming, paddleboarding, and home improvement.
Choi HY, Rahmani M, Wong BW, Allahverdian S, McManus BM, Pickering JG, Chan T, Francis GA. ATP-Binding Cassette Transporter A1 Expression and Apolipoprotein A-I Binding Are Impaired in Intima-Type Arterial Smooth Muscle Cells. Circulation. 2009;119(25):3223-31.
Francis, GA. The Complexity of HDL. Biochim Biophys Acta 2010;1801:1286-93.
Bowden KL, Bilbey NJ, Bilawchuk LM, Boadu E, Sidhu R, Ory DS, Chan T, and Frans GA. Lysosomal acid lipase deficiency impairs regulation of ABCA1 and formation of high density lipoproteins in cholesteryl ester storage disease. The Journal of Biological Chemistry 2011;286(35):30624-35.
Sandhu S, Al-Sarraf A, Taraboanta C, Frohlich J, and Francis GA. Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: A retrospective cohort study. Lipids in Health and Disease 2011, Sept 11, 10:157.
Royal College of Physicians and Surgeons of Canada Medal in Medicine (2004); University of Alberta Department of Medicine Award for Excellence in Academic Mentoring (2003); Chair, 2010 International Atherosclerosis Society Workshop on HDL