Research Pillar: Biomedical

Mona Kwong’s research focuses on gaining a better understanding of how the body responds to drugs whose molecular structure is similar to that of lipids (fatty, waxy or oily compounds that are major structural components of living cells). Mona is studying cyclosporine, a drug with a lipid-like structure that is used primarily to prevent organ rejection in transplant patients. One of the major potential complications of cyclosporine is that it can behave differently from one patient to the next. For example, a dosage that works for one person may cause toxicity in another. Previous studies have shown a link between patients’ cholesterol levels and their toxicity with the use of cyclosporine. Mona hopes to determine whether lipid transfer protein I and a protein that transports lipids such as cholesterol and is also involved in binding and transporting cyclosporine. A better understanding of this mechanism and the factors that affect it will help provide an explanation for the differences and inconsistencies seen in patients taking cyclosporine. Clinicians could then measure different cholesterol levels in patients, predict the level of cyclosporine that would cause toxicity, and adjust the dosage to prevent adverse side effects

An estimated quarter million Canadians are infected with the hepatitis C virus, a chronic disease that inflames and damages the liver and, in some people, can lead to cirrhosis or liver cancer. There is currently no effective therapy to treat hepatitis C, nor any vaccine to prevent its transmission. Morgan Martin is studying the function of the HCV NS3 protease, an enzyme required for the hepatitis C virus to make copies of itself inside a cell. Morgan hopes to better understand how this interaction works, so she can identify potential ways to interfere with its functioning. This approach, known as protease inhibition, has already proven useful in drug treatment for HIV infection and may lead to new, effective interventions for hepatitis C.

Mild electrical stimulation of various brain sites leads to the development of seizures, which intensify over time. Called the kindling phenomenon, this process has been widely studied as a model of epilepsy, neuroplasticity (learning, memory and various mental disorders) and the interictal (emotional) changes that occur between seizures in certain types of epilepsy. In his previous research, Steven Barnes demonstrated that learning plays a major role in this process. His studies show that rats learn to associate particular environments with seizures and this awareness greatly affects the intensity of seizures and interictal behaviours. People with epilepsy also tend to have more seizures in certain situations than others, a pattern that has not been widely studied. Steven is investigating how conditioning affects these responses. His research will ultimately reveal insights about the role of conditioning in the kindling phenomenon associated with epilepsy.

White blood cells are the key elements of the immune system that keep our bodies healthy. Normally these cells circulate in the bloodstream, but upon infection or injury, the cells exit from blood vessels and enter the damaged tissue to promote healing. Proteins on the cell surface, called cell adhesion molecules, take white blood cells to the afflicted site. These molecules are tightly regulated to ensure they only allow cell migration into damaged tissues. When regulation fails, cell adhesion molecules may promote inflammatory diseases such as arthritis, inflammatory bowel disease and atherosclerosis or metastasis (transfer from one organ or body part to another) of cancer. Kelly Brown is studying CD44, a cell adhesion molecule found in mice and humans on virtually all cell types. Kelly is investigating CD44 on particular white blood cells called monocytes. Once in damaged tissues, these cells eliminate pathogens and alert the rest of the immune system. She is examining the changes that occur in CD44 when monocytes are activated and how the regulation of CD44 contributes to monocyte function during an inflammatory response. Kelly ultimately hopes to learn how to block or promote CD44, which could lead to new treatments for inflammatory diseases and cancer.

Pulmonary hypertension (PHT) is a life-threatening disease; people with PHT experience shortness of breath, chest pain and fainting and live an average of 2.5 years after diagnosis. The disease involves increased production of endothelins in the lungs, which constrict blood vessels in the lungs. Endothelin is a potent vasoconstrictor (constrictor of blood vessels). Xing Cheng is investigating how certain substances produced in the lungs with PHT influence the ability of endothelin to constrict blood vessels. She is also examining how anti-inflammatory drugs that inhibit the formation of these substances affect production of endothelin. Her research will help identify drug combinations that may reverse the cardiovascular abnormalities causing pulmonary hypertension.

The Ichthyosporea are a group of single-celled parasites that infect a variety of animals, including humans. The group has only very recently been identified on the basis of some preliminary genetic data, and appears to have evolved from animals and fungi. Very little is known about these parasites, and genetic data is needed to understand their evolution and how they function. Audrey de Koning is determining the DNA sequences of some common genes in several Ichthyosporeans and comparing these sequences to the genes of other organisms. This will allow her to identify similar genetic patterns and learn more about how Ichthyosporeans evolved. She is also generating a large number of DNA sequences for expressed genes-genes that have had their coded information converted into the structures present and operating in a cell-in a representative member of the Ichthyosporea. This will give a broad picture of how these parasites function, and may uncover weaknesses that can be exploited to develop new disease treatments.