Complementary therapies are a diverse set of treatment approaches that fall outside of mainstream medicine. The majority of cancer patients – especially those with breast cancer – use a form of complementary therapies. While there is growing evidence that some of these therapies can contribute to effective cancer care, their use has not become part of standard cancer care. Patients often research complementary care options and investigate ways of integrating them in their treatment plan, without discussing these approaches with conventional health care providers. This can lead to poorly integrated care, which raises concerns about potential toxicities, adverse reactions and patients engaging in therapies with little therapeutic value. Alison Brazier is researching health care providers’ perceptions of the factors that either serve as barriers or facilitate an integrative approach to breast cancer care. Alison is conducting a series of in-depth qualitative interviews with health care providers and women living with breast cancer in four Canadian cities. She is also developing a survey instrument, to be used in a large national survey, which examines the attitudes and knowledge of complementary and conventional health care providers about integrative cancer care. The results of this study are aimed to enable a more integrative approach to cancer care in Canada that provides safer, more effective and more comprehensive cancer care.
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Investigation of the impact of HLA genetic diversity on HIV sequence evolution and clinical correlates of HIV disease
One of the major challenges facing HIV treatment and vaccine design is the virus’ capacity to mutate extremely rapidly in response to a changing environment. The course of HIV infection within a given individual is characterized by a constant, dynamic evolution of the virus. It is now appreciated that a wide range of host genetic factors influences the course of HIV infection and disease progression. The proposed research project seeks to investigate the effects of genetic variation within specific genes of the human immune system (called the “”Major Histocompatibility Complex”” or “”MHC”” genes) on the clinical course of HIV infection. The results of this project will help us gain a more detailed understanding of the multiple genetic factors that affect the course of HIV infection, and help bring us closer to the potential incorporation of human genetic information into the clinical management and treatment of this disease. In addition, this research will be of relevance in the continuing efforts to develop a vaccine against HIV. Research such as this will help us develop and implement strategies for clinical management of HIV/AIDS and will therefore ultimately be of benefit to individuals living with HIV.
Investigation of the factors secreted by feeders used in the maintenance of human embryonic stem cells
Embryonic stem cells can continually replicate themselves and also have the capacity to differentiate into other types of cells. Consequently, stem cells have the potential to replace damaged tissues in our bodies, which could revolutionize the treatment of degenerative diseases and traumatic injuries. Currently the production of human embryonic stem cells in the lab setting requires use of “feeder cells” from mice in order for the stem cells to grow. Having to depend on feeder cells limits large-scale production and also could introduce unacceptable risks in clinical applications. Dr. Nicolas Caron is investigating which proteins from feeder cells nourish stem cell growth. His goal is to develop a feeder-free culture that would be equally effective for growing stem cells. This research could lead to the development of cell-based therapies for genetic diseases, and support research into ways of shifting from organ, to cell-based transplants.
Alterations in cellular signalings in human diabetic vasculature contribute to diabetes-associated cardiovascular complications
The prominence of diabetes as a risk factor for cardiovascular complications has been rising in recent years, largely attributed to increased longevity combined with a non-active lifestyle and an unhealthy diet. Up to 80 per cent of deaths in diabetic patients are related to cardiovascular disease. The cardiovascular complications associated with diabetes occur when blood vessel walls thicken in response to changes in intracellular signaling within the vascular tissue. Dr. Ada Chung is identifying the underlying molecular mechanisms responsible for accelerated thickening of vessel walls and poor blood vessel formation, which lead to vessel blockage, hypertension, angina and other cardiovascular complications in patients with diabetes. Understanding these molecular mechanisms may be beneficial to medical innovations in diagnosis and treatment that can delay the onset and slow the progression of diabetes and its related cardiovascular complications.
The Zot system of intercellular tight junction regulation
In order to improve the effectiveness of drugs taken orally (by mouth), researchers need to understand how the lining of the gut (intestinal epithelium) functions to block drugs from being absorbed into the circulation system. The lining provides a protective barrier that selectively allows certain molecules to flow across it. While larger molecules typically are blocked from crossing the intestinal epithelium, recent evidence suggests that there may be ways of manipulating the system to optimize the uptake of drug molecules. Dr. Igor D’Angelo is investigating the permeability of the intestinal epithelium lining the gut. Permeability is controlled by sites (intracellular tight junctions) that link these cells together – it is a complex, but poorly understood structure. Research indicates that Increased permeability of the lining is associated with severe allergies, autoimmune diseases like diabetes, tissue inflammation and cancer metastasis. It also is known that several types of bacteria produce toxins that increase permeability by opening up the tight junctions between these cells. Igor’s research is directed at understanding how these tight junctions are altered and how the mechanisms underlying those changes could be exploited to improve uptake of drugs in the treatment of disease.
Development of a genetic-based prediction model for cardiovascular disease and cancer risk assessment in neurofibromatosis type 1
Neurofibromatosis 1 (NF1) is a genetic disease associated with a variety of skin abnormalities and an increased risk of developing cardiovascular disease and cancer. About one third of people with NF1 die before age 45; usually from one of these complications. However, the risk of developing cardiovascular disease and cancer is not the same in all NF1 patients, with some people at higher risk of developing these complications. These differences are seen both between families with different mutations of the gene that causes NF1 and within families with the same mutation. Alessandro De Luca is exploring whether certain specific alterations of the NF1 gene and differences in other genes that interact with the NF1 gene are linked to an increased risk of cardiovascular disease and cancer. Alessandro is studying the frequency of particular NF1 mutations and variants of interacting genes in NF1 patients with and without cancer and cardiovascular disease. The ultimate aim of his research is to develop a panel of genetic markers that can be used to predict the risk of developing cardiovascular disease or cancer in patients with NF1.
Supporting Success: The Role of Mentorship in Increased Health Services Research Capacity
Research programs in Canada embrace mentorship as a way to increase research capacity, with experienced researchers mentoring more junior investigators. The three major research granting agencies in Canada (CIHR, SSHRC and NSERC) identify mentorship of new researchers as integral to research training. But few questions have been asked about how to make mentorship effective. For example, is an effective mentor someone who oversees career development, or provides guidance for a trainee? Dr. John Egan is evaluating how mentorship works in collaborations between university and community-based researchers. He is examining how mentors and their trainees experience mentorship, in a program jointly funded by the Canadian Institutes of Health Research and MSFHR. This research should identify what creates successful, productive mentoring, and lead to evidence-based practices and policies for effective mentorship
InnateDB: A Systems Biology Approach to Understanding the Pathogenomics of Innate Immunity
Although humans come into contact with pathogens (disease-causing microorganisms) regularly, these encounters only rarely result in infections. Most of the time, our innate immune response system quickly eradicates potentially harmful bacteria. Innate immunity is always available, rapidly turned on, and effective against a broad range of pathogens. However, the innate immune response can also lead to tissue damage and sepsis (bloodstream infection) if over-stimulated. For her PhD research, Jennifer Gardy fine-tuned PSORT-B, a software program she developed. The program examines the biological features of proteins in disease-causing bacteria to predict where they will most likely reside. As a Post Doctoral Fellow, Jennifer is creating a computer model of the genes and proteins that comprise the innate immune system and their interactions with each other. The model will enable her to predict the effect of removing a specific gene on the immune system as a whole. This research could reveal important insights about the functions of many of the genes involved in innate immunity, and lead to the development of novel therapeutic approaches to treat a broad range of bacterial infections and autoimmune disorders.
Neuronal astrocyte interactions underlie cerebral vasculature control
How brain cell activity alters blood flow in the brain is unclear, even though the phenomenon was first reported in 1890. Astrocytes are major support cells in the brain, that form enlarged, club-shaped endings called endfeet. These endfeet wrap around all blood vessels, giving them the opportunity to control blood vessel diameter. A recent discovery has shown that changes in calcium levels in the endfeet trigger dramatic constriction in blood vessels. Although nerve cells can initiate this process by signalling to the endfeet, prolonged nerve cell activity can also result in the blood vessels dilating to supply oxygen and other nutrients to the nerve cells. Dr. Grant Gordon is investigating how nerve cell activity counters the constriction caused by the astrocytes to increase the diameter of blood vessels. His goal is to determine whether signals from the nerve cells inhibit constriction, information which could lead to new drugs for people with impaired or damaged cerebral blood vessels, such as stroke patients.
Innate and adaptive immune responses of mast cells during Salmonella infections
Mast cells are part of the body’s immune system, residing in connective tissue and releasing compounds during allergic reaction or in response to injury or inflammation. They are found throughout the body, particularly at sites where pathogens can gain access, such as the gastrointestinal tract and the skin. As one of the first inflammatory cells to encounter an invading pathogen, they play a critical role in innate immunity and defense. Guntram Grassl is examining the role of mast cells in Salmonella infections to increase understanding of how these bacteria interact with host cells and how these interactions result in disease. He is determining how mast cells are activated in response to Salmonella and characterizing which factors mediate these effects. He is also studying how infections progress in the absence of mast cells. An increased understanding of how Salmonella causes disease may ultimately lead to the development of new ways to boost the innate immune response against bacterial infections and may lead to the development of new drugs that interfere with the way pathogens trigger disease.