Program: Scholar

Coxsackievirus infections can cause a variety of illnesses, including heart disease. In North America, the coxsackievirus is estimated to cause up to 30 percent of new cases of dilated cardiomyopathy, a condition in which the heart becomes enlarged and pumps less strongly. Dr. Marc Horwitz is studying how viruses such as coxsackievirus can induce autoimmune diseases such as chronic heart disease, and how immune system components shape and control development of the disease. Studies have shown that the body’s immune response has a profound effect on the development of chronic heart disease after infection with the virus, revealing that immune cells and antibodies that attack infection also damage heart tissues. Dr. Horwitz is examining how innate and adaptive immune responses following viral infection contribute to development of chronic heart disease. He will use findings from the study to design and test new methods to prevent heart disease, which could also lead to new treatments.

Tumour suppressor genes, such as ING1, help regulate normal cell growth by encoding proteins that inhibit abnormal proliferation of cells. Dr. LeAnn Howe is studying the molecular properties and function of ING1 proteins to understand the processes that lead to the development and growth of tumours. Research has linked ING1 proteins to modification of histones, the main protein component of chromatin, which makes up our chromosomes and genes. Evidence suggests that defects in regulation of chromatin structure may improperly activate or silence genes, leading to disease. Dr. Howe is examining the way ING proteins interact with chromatin to determine whether the proteins can modify chromatin. This research could help explain the role of ING1 genes in cancer development and contribute to new cancer therapies.

Canada has a growing diabetes epidemic, which costs the Canadian health care system an estimated $13 billion annually. More than two million Canadians have the disease, and by 2010, the number is expected to increase to three million. Diabetes is also a major health problem worldwide. Although diabetes can be treated with insulin, a cure for this devastating disease remains elusive. All forms of diabetes are associated with the loss of functional pancreatic islet cells. However, very little is known about the underlying factors controlling how and why pancreatic islet cells die. Dr. James Johnson recently discovered important networks of molecules that control survival of islet cells. For example, one such network includes the RyR2 protein, which controls the release of calcium in the cell, and the calpain protein, which can split other proteins in response to increased calcium. Dr. Johnson is comparing the role of this survival network to other molecular networks to investigate how pancreatic islet cells die. The research could lead to better therapies for diabetes, including more successful pancreatic islet transplantation, a promising experimental treatment that depends critically on the continued survival of the donated cells. The findings could also improve understanding of other diseases where calcium is involved in cell death, such as heart failure, Alzheimer’s disease and stroke.

Parkinson’s disease is a chronic, progressive disorder that affects about 100,000 Canadians, at an annual cost of more than $2.5 billion. The disease involves loss of both brain cells and chemicals that modulate communications between brain cells – causing not only motor symptoms of tremor, stiffness, and slow movements but also cognitive and behavioural changes. Conventional drug therapy for Parkinson’s disease replaces dopamine in the brain. Although most motor deficits usually improve after therapy, more than 50 percent of patients (particularly those in the later stages of the disease) may develop difficult problems, such as involuntary movements, dementia and psychosis. Dr. Chong Lee is studying neural mechanisms of these complications, which are resulting from the disease itself or the chronic use of Parkinson’s drugs. Dr. Lee is also evaluating the effectiveness of neuro-protective treatment, a strategy to prolong the survival of injured cells and slow the progression of Parkinson’s disease. He ultimately aims to develop strategies to treat dementia and behavioural symptoms of the disease and to reduce or prevent treatment-induced complications in patients with Parkinson’s disease.

Cells must accurately duplicate their chromosomes (genes in the cell’s nucleus) and segregate them equally to daughter cells for proper cell growth and division. Errors in segregation results in cells with abnormal numbers of chromosomes (aneuploidy), which can lead to birth defects, Down’s syndrome and cancer. Cells have developed safeguards to ensure chromosomes are accurately segregated. A region of each chromosome called the centromere is bound by kinetochore proteins which attach to spindle microtubules, tiny fibres that pull newly separated chromosomes to each side of a dividing cell. If any mistakes occur in spindle attachment, kinetochore proteins signal the spindle checkpoint machinery, which delays segregation until the defects are corrected. Using yeast as a model, Dr. Vivien Measday is studying how kinetochore proteins attach to spindle microtubles and communicate with the checkpoint machinery. The research will improve understanding of chromosome segregation and could lead to treatments for diseases caused by abnormal numbers of chromosomes.