Regulations of the endocannabinoid receptor system of glucocorticoid hormones: Implications for Schizophrenia

The onset and development of many mental illnesses, such as schizophrenia, are believed to be affected by stress and the hormones produced as a result of stress. Research has shown that these stress hormones act upon receptors in the brain that interact with the endocannabinoid system. The endocannabinoid system is a neurochemical system which contains receptors that respond to both cannabis (marijuana) and naturally produced substances known as endocannabinoids. People with schizophrenia have been shown to have elevated levels of naturally-occurring endocannabinoids, and there is evidence that alteration of the endocannabinoid system through the use of marijuana reduces the effectiveness of anti-psychotic medication. Matthew Hill is investigating links between the endocannabinoid system, exposure and hormonal responses to stress and the development of schizophrenia. Matthew’s research may improve understanding of the neurobiological mechanisms involved in schizophrenia and suggest future treatments to manage this mental illness.

Role of Nrf2 mediated transcriptional events in neuroprotection during stroke

Free radicals are potentially damaging molecules produced in cells, particularly in response to injury. Certain free radicals cause tissue damage and trigger cell death. To combat the effects of free radicals, healthy people produce adequate quantities of antioxidants, scavenging enzymes that defend cells from free-radical destruction. When a person suffers a stroke, free radicals known as reactive oxygen species may cause cell death in large areas of the brain, resulting in brain damage and disability. It is believed that by increasing the number of antioxidants in the brain, cell death and damage following stroke might be minimized. Sophie Imbeault is working to clarify the role of the transcription factor Nrf2, which regulates the production of antioxidants in the brain. By studying the basic mechanisms underlying Nrf2 activation both during normal functioning and during stroke, she hopes her work will ultimately point to new treatment possibilities for minimizing stroke damage.

Toxicogenetic analysis of valproic acid-associated hepatotoxicity in pediatric epileptic patients

Valproic acid is a drug that has been used successfully for the treatment of many types of seizures. Yet for some patients, the drug is associated with liver failure. Clinicians are not able to predict which patient will be at risk for this serious and sometime fatal side effect, but it is known that liver failure is more common in the very young patients and when the drug is used together with other anticonvulsants. Tony Kiang is studying the possibility that individuals could have a genetic predisposition for developing liver failure following valproic acid therapy. In his research project, Tony will be using advanced genomic technologies to test this hypothesis. Results from this research will help clinicians identify which patients are suitable to be prescribed valproic acid.

Mechanistic investigations of retaining glycosyl transferases from Neisseria meningitidis and Saccharomyces cerevisiae

The complex arrangement of carbohydrates that cover the surface of cells is known to play a key role in gene activation and cell-to-cell recognition processes. Changes in the composition of these carbohydrates can lead to many pathological conditions, including the proliferation of cancerous cells and compromised immune function. Research suggests that elevated activity in the enzymes that place these carbohydrates on the cell surface is primarily responsible for changes in cell surface composition, however, the chemical mechanisms these enzymes use to function are not well understood. Working in collaboration with the McGill Cancer Centre in Montreal, Luke Lairson is researching how these enzymes function. This knowledge may be used to design effective new drug therapies to inhibit enzyme activity and help prevent and treat various human diseases ranging from cancer to AIDS.

Identification of Phosphoregulation pathways involved in Hematopoetic Stem cell self-renewal

In recent years it has been suggested that hematopoietic stem cells (HSCs) possess the ability to develop into different types of tissue in the body. Conceivably this phenomenon could one day facilitate treatment of a variety of degenerative diseases via harvesting a patient’s own HSCs, genetically modifying them, and then transplanting them back into the body. Unfortunately at present there is no effective way to maintain HSCs outside of the body, as the cells self-renew only in response to the unique combination of growth factors present within the specialized environment of the bone marrow. Michael Long is comparing how different environments affect the pathways by which HSCs receive chemical signals to renew. By studying HSC activity within bone marrow as well as an environment that does not promote HSC renewal such as the spleen he hopes to determine which signalling pathways are vital for HSC renewal. Ultimately, this information may allow researchers to identify how to recreate an environment outside the body that promotes HSC growth.

Facial indicators of heart rate reactivity in a stress induced state

Studies show that stress can increase the risk of heart disease and other conditions. Therefore, identifying people who are most likely to have strong reactions to stress is an important goal in the prevention of heart disease. David Nordstokke believes facial expressions may be key markers for identifying people at risk of stress-induced heart disease. He is studying the relationship between facial expressions and stress by giving participants a test of social anxiety. During the videotaped test, David compares changes in heart rate with specific facial movements to determine if there is a link. He hopes the research will reveal patterns of facial expression that provide information about heart rate reactivity. Ultimately, David aims to help health care practitioners in the early detection of individuals at risk of developing heart disease so they can intervene with stress management programs.

Finding the metaphorical road back to health: Understanding the illness experience and locating the means of recovery

MSFHR Distinguished Scholar Michael Chandler is researching individual and cultural factors that could help reduce the high rate of suicide among youth in certain First Nations communities. His research is directed at understanding the ways cultural differences help or hinder young people’s ability to insulate themselves from risks of self-injury and suicide. With Dr. Chandler as his supervisor, Jesse Phillips is building on the focus of this research by examining how Aboriginal and non-Aboriginal youth view the relationship between their health and well-being, and the health and well-being of their community and culture as a whole. Jesse is exploring the notion that Aboriginal youth understand their health and well-being in ways that are more rooted in community life and cultural tradition than is ordinarily the case for non-Aboriginal youth. Achieving a better appreciation of such cultural difference could work to ensure that the health concerns and ability of First Nations youth are more adequately met by means sensitive to their cultural diversity.

Coping in serodiscordant couples: the role of HIV-negative partners' coping strategies in health outcomes of their HIV-positive partners

Effective anti-retroviral drug regimes are helping people with HIV live healthy for longer periods of time. As a result, people with HIV are increasingly able to enter long-term relationships, a development which has implications for the course of their disease. For example, there is research indicating that people with HIV have a higher risk of their disease progressing when they perceive negative support from family or friends. Eli Puterman is examining coping methods in relationships involving an HIV-negative person with a HIV-positive partner. He is studying how these couples cope with both HIV disease and the interpersonal problems that emerge from the illness. Eli hopes to reveal insights about how the interaction of coping methods affects the mental and physical health of people with HIV. The research will help identify coping strategies that either buffer the effects of HIV disease or contribute to increased suffering. The study could also help improve mental health treatments for couples coping with chronic illnesses in general.

Role of DNA methylation and histone modification in the transcriptional regulation of mouse Ly49 genes

Natural killer (NK) cells are a subset of white blood cells and are part of the innate immune system. Their activation, unlike that of the adaptive immune system, does not require exposure to a foreign substance. NK cells are considered a first line of immune defense in the body, as they can recognize and destroy altered cells such as virus-infected or tumour cells. On the surface of normal cells there are receptor molecules called MHC class-I, which are recognized by receptors on the surface of NK cells. The interaction of NK receptors and MHC class-I prevents NK cells from destroying normal cells. NK cells are able to destroy virus-infected cells and cancer cells because in these cells, MHC class-I molecules are often not expressed (shut off). In both human and mouse, the repertoire of receptors varies among different NK cells. To better understand how NK genes are regulated, Arefeh Rouhi is studying the mechanisms that control these variations among NK cells. Ultimately, this knowledge may lead to ways to use the body’s own immune system to protect against infections and malignancy.

Immunomodulation using the modified transporter associated with antigen processing (TAP)

The immune system constantly monitors all cells in the body to identify and eliminate any cell that becomes infected or cancerous. A key component of the immune system is a transporter called TAP, which resides inside the cell on the membrane of a compartment called the endoplasmic reticulum (ER). Normally, TAP imports protein fragments called peptides into the ER, after which they are displayed on the cell surface and examined by immune system cells. If the immune system recognizes peptides derived from a virus or tumour, the cell is destroyed. In many cancer cells, TAP is present in very low levels, so viral or tumour peptides do not get into the ER for identification. As a result, the T cells that recognize and kill aberrant cells are not activated and diseased cells continue to grow. At the opposite end of the immunity spectrum, T cells may identify cells from a donor organ as being foreign to the host’s body and kill these cells, resulting in transplant rejection. Robyn Seipp is investigating whether different forms of TAP can be used to improve the immune system’s ability to recognize and respond appropriately to both tumour cells and donor cells from a transplanted organ. The results may be used to improve cancer treatments and reduce transplant rejection.