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.
Program: Trainee
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.
The importance of visual speech information in the recognition of one's native language
Infants are inundated with visual and auditory information that is critical to their development of communication. One important communication skill that infants learn is the ability to discriminate between their native language and an unfamiliar language. Whitney Weikum is studying whether infants can develop the ability to discern people speaking in the infants’ native language, versus other languages, based solely on visual information. The research involves conducting imaging studies that will determine the neural processes responsible for analyzing visual information. Results from the study could help create definitive tests for patterns of normal communication development. Such tests could lead to early identification and treatment of infants with disorders such as Autism.
Effect of glucagon-like peptide-1 on islet transplantation
More than two million Canadians and 135 million people worldwide have diabetes, a chronic medical condition characterized by a lack of insulin to regulate blood sugar levels (Type 1), or insensitivity to insulin (Type 2). Transplanting islets, the cells in the pancreas that produce insulin, can cure Type 1 diabetes. But use of this therapy is limited because of the huge volume of islet tissue required to treat all Type 1 diabetics. As a result, most continue to rely on insulin injections to help control blood glucose. Glucagon-like peptide-1 (GLP-1) is produced in the intestine and has numerous anti-diabetic effects. Clinical trials are currently investigating GLP-1 as a treatment for Type 2 diabetes. Other recent studies show GLP-1 also enhances the growth of islet tissue. Rhonda Wideman is investigating the effects of GLP-1 on the growth and survival of transplanted islets to determine if GLP-1 reduces the amount of islets needed to cure Type 1 diabetes in transplant recipients. If so, more islet tissue could be produced and more patients could be treated with this procedure.
Development of a non-viral DNA cancer vaccine by combining liposome-mediated gene and immunostimulatory oligonucleotide delivery technologies
Vaccines offer a promising approach to prevent and treat cancer. Vaccines have the potential to overcome the failed immune response to cancer cells by priming the immune system to recognize and destroy these cells. But two issues hamper the success of generating cancer vaccines: the difficulty in identifying an appropriate tumour associated antigen (TAA) that would induce an anti-tumour response; and the availability of a safe but potent adjuvant (partner) therapy to boost the immune response against the antigen. Kaley Wilson is researching ways to overcome these obstacles and allow the creation of a non-viral DNA cancer vaccine. To accomplish this, she is using two lipid, or fat-based delivery systems to introduce TAA and adjuvant therapies into tumour cells. The combination of these two lipid-based technologies could support the development of a vaccine targeting a variety of cancers.
Dose corrections for inhomogeneities in small field intensity modulated x-ray radiation therapy
Alanah Bergman’s research focuses on the use of high energy x-ray radiation in cancer treatment. Radiation fields are shaped to deliver high doses that conform closely to the shape of the tumour being targeted. A new technique called Intensity Modulated Radiation Therapy (IMRT) uses a collimator to fine-tune the shape and intensity of the radiation field. But it is difficult to accurately calculate the dose for small fields, especially when inhomogeneous tissue — such as lung, air or bone — is included in the treatment area. Alanah Bergman is investigating methods for improving dose calculations for x-ray radiation treatment. She will quantify errors in dose calculations and modify the calculations to improve their accuracy. Results from the study could provide radiation oncologists with better tools for making treatment decisions and ultimately benefit patients receiving radiation therapy for cancer, particularly cancers of the head/neck, lung and breast.
Examining health care interactions for their influence on effective and equitable perinatal health care services for women and families
Research has shown that quality of health care services influences the health and well-being of women and their families during pregnancy, birth and the first two to three months after birth. Studies also show that access to effective health services is important in helping women follow healthy practices. Less is known about the ways in which relationships between women and their health care providers influence the effectiveness and fair distribution of health services. Helen Brown is investigating this question, with a focus on understanding how these relationships affect healthy practices among women from marginalized or less powerful groups. Helen hopes the research will help improve health care relationships, enhance quality of care, strengthen health promotion and education for childbearing women, and help policy-makers create more effective and equitable services.
Molecular mechanism of genomic instability and telomere shortening in Dog-1 mutants
BRCA1 is a breast cancer susceptibility gene found in more than 80 per cent of families in which six or more family members have had breast cancer. A protein that interacts with this gene is very similar to a specialized enzyme, called a helicase, in the worm. Iris Cheung and her colleagues have demonstrated that the helicase is required to prevent the loss of DNA that is rich in guanine (one of the four components of DNA). Without the enzyme, DNA is lost in multiple sites in the worm genome, resulting in genetic instability and opening the door for normal cells to develop into tumour cells. Iris Cheung is researching how the prevention of genetic mutations in the worm may provide clues to how mutations arise and are prevented in the gene known to cause breast cancer. Findings may help improve researchers’ understanding of the development and properties of breast cancer, and potentially the development of new therapies.
Functional role of p33ING1 phosphorylation in cellular stress responses to DNA damage
The organization of DNA sequences within a structured framework is vital to maintain the stability of a cell’s genetic material. When DNA damage occurs and is left unrepaired, it can affect cell division and normal cellular functions and ultimately lead to cancer. Eric Campos is expanding previous knowledge generated in Dr. Gang Li’s lab around a tumour suppressing protein known as p33ING1. This protein has been found to play an important role in the cell’s response to ultraviolet radiation, enhancing the repair of UV-damaged DNA. Eric’s research focuses on the biochemical processes by which p33ING1 is activated. This work could lead to novel treatments for cancer, a disease caused by the onset of genomic instability.