Alberta Innovates- Health Solutions

Dr. Gordon Francis, (front) and his research team, (left to right) Audic Moses, Ethel Reteff, Ryan Perry, Dr. Dawn Macdonald, Tim Terry, and Dr. Wen Qi Wong.

Dr. Gordon Francis had a hard time choosing between a career as a physician or one as a basic medical researcher. Happily, he is able to combine both as a Heritage researcher studying lipids and as an endocrinologist specializing in lipid disorders. He emphasizes that the strength of lipid research at the University of Alberta, support from the Faculty of Medicine, and funding from AHFMR were what drew him to Alberta in 1994.

His focus on cholesterol comes from his physician's concern about the enormous loss of life from heart disease and stroke. His researcher's curiosity was intrigued by the role that high-density lipoproteins (HDL, also known as "good cholesterol) plays in the risk for heart disease. People can raise their HDL levels through weight loss, aerobic exercise, and, for post-menopausal women, estrogen replacement. Dr. Francis comments, "There is an inverse relationship between HDL and the risk for heart disease. The more HDL you have, the more protected you are. So if you have a low level of HDL you are at greater risk for heart disease no matter how low your LDL 'bad' cholesterol, reading is. The protective action of HDL seems to override the negative effects of LDL."

Yet most of the drugs used to treat high cholesterol problems target lowering LDL. The protective action of HDL has not been exploited for the treatment of heart disease, a situation Dr. Francis hopes to see changed through his research into how HDL works, and what triggers its production in the body. It's a new frontier for lipid research because HDL is still not well understood. What scientists do know about HDL is that it turns on the removal of cholesterol from artery walls. Once removed, the cholesterol is sent to the liver to be excreted as bile.

Dr. Francis has found a way of modifying HDL so that it's even better at initiating cholesterol removal. "The 'super' HDL not only picks up cholesterol from the cell surface, but signals cholesterol to move from within the cell to the outer membrane pick-up site. This decreases the amount of cholesterol inside the cell and makes more cholesterol available for pick-up by newly secreted HDL. When these new HDL particles get larger by removing cholesterol, they aren't cleared from the bloodstream as quickly, which increases the level and, therefore, the protective actions of HDL."

The protective action of the altered HDL could potentially be used to help fight heart disease, especially since similarly altered HDL may occur naturally in the body in certain situations, including inflammation. Dr. Francis is testing the actions of HDL found in fluid from the knee joint of people who have rheumatism. This naturally occurring HDL has the same key protein as his laboratory-altered HDL, and shows the same super-efficient cholesterol-removing properties as well.

Dr. Francis and his colleagues are concentrating on developing this modified HDL protein with the help of Dr. Robert Hodges in the Protein Engineering Group. The Francis lab is also testing the HDL to see if it actually retards the development of atherosclerosis. Their goal is to develop new therapies for the treat- ment of coronary heart disease and stroke.

Dr. Gordon Francis is a Heritage Clinical Investigator. He also receives support from the MRC and Daiichi Pharmaceutical Inc.

Relevant websites about cholesterol levels:
Cardiac Prevention and Rehabilitation Research Centre (Canadian)
http://adminweb.ucis.dal.ca/cprrc/cholest.htm

Doctor's Guide to Elevated Cholesterol Information and resources
http://www.pslgroup.com/ELEVCHOL.HTM