This multi-disciplinary unit is focused on improving current treatment of fractures, developing and implementing primary and secondary prevention strategies and developing new knowledge about mechanisms underlying bone health and disease. This includes research exploring the role of bone mineral as an important determinant of joint health. The unit’s goal is the development and translation of new knowledge to optimize bone health and minimize the burden of osteoporosis and fracture.
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This unit’s overall mission is to advance understanding of the human immune response involved in transplantation and mitigation of infectious diseases. The unit brings together a multidisciplinary team of basic scientists, clinicians and health professionals who are undertaking basic and translational research involving molecular and cellular mechanisms of immunity. Their goal: to improve transplantation outcomes and the ability to understand and deal effectively with infectious diseases.
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Serious mental disorders affect thinking, mood and behaviour. The consequences are suffering, impaired function in daily life and yearly costs estimated in Canada at tens of billions of dollars. Like diabetes, hypertension and asthma, mental disorders are complex disorders, meaning there is no single gene mutation, experience or environmental effect that can be held responsible. With a history of focused but isolated research strategies that have failed to address these complexities, present day treatments for schizophrenia and bipolar disorder are no more effective than those developed 50 years ago. There is also a lack of effective treatments for Alzheimer’s disease. The Centre for Complex Disorders (CCD) will seek integrative and transformative solutions to these health problems, with an initial focus on psychotic illnesses, such as bipolar disorder and some types of depression. These often begin in adolescence and cause those affected to lose contact with reality, and chronically become socially isolated and unable to work. The unit’s secondary focus will be complex disorders affecting memory in old age.
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Transplantation is the treatment of choice for many forms of end-stage organ failure and cancers of the immune system. Due to the difficulty in finding fully compatible donors, the patient’s immune system must be suppressed with drugs to prevent it from rejecting the transplanted tissue. While necessary, these drugs suppress all immune response, causing serious side effects including increased risk for infections, cancers, damage to kidneys, hypertension, diabetes and seizures. Dr. Megan Levings is looking for a way to protect the transplanted tissue without compromising other aspects of the normal immune response. She is studying a novel class of white blood cells, known as T regulatory (Tr) cells, which are thought to have the ability to selectively suppress immune responses. Dr. Levings is exploring the molecular and cellular biology of Tr cells to better understand how they develop and act to induce an immune response. Potentially, these cells might be the basis for a more directed approach to controlling rejection.
Retinitis pigmentosa (RP) is a form of inherited blindness that results from the death of light-detecting neurons called rod cells. It is usually diagnosed in children, adolescents and young adults and typically begins with night blindness followed by progressive deterioration of peripheral vision (tunnel vision). Dr. Orson Moritz is studying transgenic frogs with the same genetic mutations that cause the condition in humans. His goal is to identify the biochemical pathways that are activated by these mutations and lead to the death of rod cells. To confirm the involvement of these pathways, he is studying transgenic frogs in which these pathways are disrupted to determine whether this prevents development of RP. The research could enable design of therapies to prevent the progression of RP in humans.
Physical activity can help prevent a host of chronic diseases, including osteoporosis and obesity, two major medical conditions that likely begin with childhood inactivity. But it’s estimated that three out of five Canadian youths between five and 17 years of age are not physically active enough to ensure optimal growth and development. Weight reduction programs targeting children who are already obese have largely been unsuccessful, which indicates the need for a stronger focus on developing more effective prevention strategies. Several studies have shown that school-based programs can effectively improve bone health. Dr. Heather McKay is evaluating the impact of innovative physical activity programs on bone health and weight of elementary school children, research that could lead to the development and implementation of public health programs to encourage physical activity and improve the health of Canadian children.
Research has shown that psychosocial treatments, such as cognitive-behavioural therapy, can reduce symptoms and improve overall well-being of people who are experiencing a first psychotic episode. Yet, studies also show that only about one-third of potential candidates for treatment agree to participate in and complete the therapy. Dr. Tania Lecomte is exploring why some individuals experiencing a first psychotic episode refuse or fail to adhere to treatment. Besides assessing whether or not motivation enhancement therapy improves adherence to treatment, she is also evaluating the impact on symptoms and patient well-being when they receive both motivation therapy and cognitive-behavioural therapy, or just the latter. If motivation therapy is shown to be effective, results from the study could help young people cope better with psychotic symptoms. Her research may also reveal new information about factors that motivate individuals with psychotic symptoms to seek help.
Prostate cancer is the second leading cause of cancer-related deaths in men. Advanced prostate cancer is often treated with androgen withdrawal therapy, which blocks the growth-promoting effects of androgens (such as testosterone). Unfortunately, the cancer eventually progresses to an androgen-independent state, allowing for tumour growth without androgens. Dr. Michael Cox is studying how prostate tumour cells with neuroendocrine characteristics contribute to the disease’s progression to androgen independence. His research aims to understand how these cells develop within prostate tumours, what effect such cells have on the growth rate of prostate tumours, and how hormones secreted by these cells influence therapeutic resistance and metastatic preferences during disease progression. Dr. Cox is also working to determine the molecular mechanisms by which prostate tumour cells develop genetic mutations and become less susceptible to cancer treatment. He is identifying how tumour cells respond to growth factors in the presence or absence of testosterone and the cellular changes that allow prostate tumour cells to utilize these growth factors to aid development of testosterone independence.
While there has been significant research conducted about how bacteria and viruses cause disease, in comparison, relatively little is known about eukaryotic pathogenic processes – specifically, the disease-causing mechanisms of parasitic protozoans, which are single-celled, nucleated organisms. Dr. Michael Grigg is investigating the protozoan parasite Toxoplasma gondii, a common eukaryotic pathogen capable of infecting essentially any nucleated cell in most warm-blooded species. This highly successful parasite currently infects close to one-third of the human population. There are only three main strains of the parasite in nature and each line causes profoundly different disease in animals. Toxoplasma is known to stimulate a variety of immunological responses in infected hosts. Hosts are unable to clear the parasite, resulting in a life-long infection. Dr. Grigg is studying the immunological and molecular interactions that modulate Toxoplasma pathogenesis in an animal model of the disease, and identifying the virulence factors that are essential to the success of particular strains of the pathogen. From his work, he hopes to uncover new mechanisms and principles of pathogenesis.
Much of the resurgence of tuberculosis during the past decade can be attributed to the fast spread of new bacterial strains that are resistant to the conventional anti-tuberculosis drugs. New therapeutic strategies are urgently needed, requiring a better understanding of the interaction of the causal agent, Mycobacterium tuberculosis, with the host cells. Monocyte/macrophages are the principal targets for mycobacterium. These cells possess a powerful intracellular killing mechanism and play an essential role in the clearance of bacteria. However, one of the major features of tuberculosis pathogenesis is the residency of bacteria in an intracellular vacuole that evades intracellular killing. Mycobacterium tuberculosis interacts with specific cell surface molecules, acting as “”an entrance gate”” and ultimately producing factors that inhibit the intracellular killing. Dr. Zakaria Hmama’s research focuses on the molecular mechanisms regulating the entry of the bacteria into macrophages and the resistance to intracellular killing. Such studies will provide a rational basis for the development of new drug strategies.
