John Pospisilik’s research centres on glucagon, an important hormone involved in regulating blood sugar levels between meals. Glucagon prevents hypoglycemia (low blood sugar) by releasing sugar stored in liver, fat and muscle. While type 1 and type 2 diabetes both involve excessive release of glucagon, until recently, little was known about how the body inactivates and clears glucagons from the blood stream. Pospisilik contributed to research that showed the DP IV enzyme may inactivate glucagon. Now using state-of-the-art and conventional techniques, he is examining the process in which DP IV may inactivate and clear glucagon, and developing tools to measure active glucagon. He hopes this research will lead to novel treatments for diabetes.
Year: 2001
The role of SHIP in normal and aberrant macrophage and osteoclast development and function
Michael Rauh believes the best approach to health research is to acquire insights from patients, and then to explore those insights in the laboratory. That’s why he’s enrolled in a combined MD/PhD program at UBC to become a clinician-scientist. Rauh’s research focuses on the molecular pathways that lead to the development of cancer cells. His particular interest involves the SHIP gene and its possible use as a therapeutic target in the treatment and prevention of leukemia and other diseases such as osteoporosis. Rauh is investigating whether SHIP can inhibit development of the diseases by preventing inappropriate cell growth. The research will contribute to his ultimate goal of learning how to identify cancer at its earliest, most treatable stages to enable more effective preventative strategies.
Growth and Signaling pathways involved in prostate cancer progression
Prostate cancer is the second leading cause of death in North American men. Treatment of the disease often involves blocking testosterone, an important regulator of cell survival and division in the prostate. But prostate tumours can eventually survive and grow even without testosterone, and once this occurs, there is no alternative therapy. Dr. Sandra Krueckl is investigating changes within cells that lead to testosterone-independence and progression of prostate cancer. She is also exploring evidence that suggests insulin-like growth factor 1 (IGF-1), and cellular signalling molecules influenced by IFG-1, are key to the development of testosterone-independence. By illuminating these genetic changes, Krueckl hopes to identify molecular targets for cancer prevention and treatment strategies.
The Role of Presenilin Genes in Learning and Memory in C. elegans may Reveal Early Occurring Memory Deficits in Alzheimer's Disease
Jacqueline Rose aims to answer crucial questions about learning and memory loss associated with Alzheimer’s disease. In the later stages of the disease, patients’ memory and cognitive abilities decrease, eventually leading to dementia and death. Early detection of Alzheimer’s is difficult because a large amount of brain dysfunction must occur before memory and cognitive disabilities become evident. However, researchers have been able to link mutations in a group of genes, called Presenilins, to the most aggressive form of Alzheimer’s, called Familial Alzheimer’s Disease. Two presenilin genes have been identified in the microscopic worm Caenorhabditis elegans. Rose is using C. elegans as a model to analyze how mutations in these genes affect learning and memory. She hopes knowledge from this research will help characterize learning and memory deficits of Alzheimer’s patients during the early stages of the disease.
Characterization of murine macrophage responses to Salmonella typhimurium infection
Carrie Rosenberger’s research focuses on Salmonella, the bacteria responsible for an estimated 16 million cases of typhoid fever worldwide each year. Research has shown that Salmonella typhimurium, a strain of the bacteria, causes widespread disease by penetrating the inner membrane of the intestinal wall and residing in macrophages (immune cells that normally help destroy bacteria). Rosenberger is investigating how Salmonella typhimurium avoids destruction by altering macrophage genes. To study the complex interactions between cells and the bacteria, she is using gene arrays, technology that enables simultaneous measurement of how hundreds of macrophage genes change during infection. Rosenberger hopes the research will increase understanding of how Salmonella causes disease and helps in the design of more effective treatments. She also hopes to broaden knowledge of how cells and pathogens (disease-producing organisms) interact.
Molecular Basis of Mammary Epithelial Cell Polarization
Aruna Somasiri has long been interested in how cells function at the molecular level. Somasiri believes understanding errors in cell regulation will provide the most valuable information in designing treatments for cancer. He’s contributing to that knowledge by investigating the process that causes benign cancer tumours to metastasize – travel from their original tissue and form secondary tumours that are difficult to eliminate. Research has revealed that certain disruptions to cellular activity influence this process. Somasiri aims to understand the normal process of differentiation – cells forming other cells – in breast cells. He hopes the research will reveal insights about how misregulation of the process can initiate breast cancer metastasis.
Prediction and prevention of autoimmune diabetes mellitus
Jacqueline Trudeau’s research focuses on autoimmune disease – disorders that cause the immune system to destroy normal body tissues. She’s specifically interested in how a specific type of immune cell, T-cells, are mistakenly activated in autoimmune disorders. Type 1 diabetes is an autoimmune disease in which T-cells destroy insulin-producing B-cells in the pancreas. This leads to hyperglycemia (high blood glucose), insulin dependence and other complications associated with diabetes. Given that autoimmune diseases may develop and be present for years before being diagnosed, they are difficult to treat. It is also challenging to understand how the disease process is initiated and the course of development thereafter. Jacqueline is developing techniques to identify T-cells that specifically destroy B-Cells before hyperglycemia sets in. She aims to design an approach for identifying children at the early stage of developing diabetes, a critical window of opportunity when treatment could save remaining B-cells
Pathogenesis and Treatment of Huntington's Disease
There is currently no effective treatment for Huntington’s disease, a progressive and ultimately fatal neurological disorder caused by a defect in the Huntington Disease gene. Symptoms of the inherited disease, which usually appear at mid-life, include abnormalities in movement, difficulties with awareness and judgement, and emotional instability. Using genetically altered mice, Jeremy Van Raamsdonk is investigating the underlying genetic and cellular changes that give rise to Huntington’s disease and potential treatment strategies. The research involves testing both drug and gene-based treatments targeted at the root cause of the disease, as well as assessing treatments to minimize the damage to the nervous system. By developing specific treatment strategies, Van Raamsdonk aims to limit damage to nervous system cells and increase the lifespan and quality of life for people with Huntington’s disease.
Regulation of inhibitory receptor gene expression by Natural Killer cells
Natural Killer (NK) cells play an important role in the immune system: targeting and destroying tumour and virus infected cells that evade other branches of the immune system. Brian Wilhelm is striving to understand what regulates the ability of NK cells to distinguish between abnormal cells and healthy cells. While it’s known that receptors on NK cells enable them to distinguish between cells, there is little knowledge about the genetic mechanisms that direct the process. He hopes that the research on receptor genes will provide insights about how individual genes and sets of genes specific to NK cells are regulated. As well, the work may shed light on the role of receptor genes in developing blood disorders and also about the use of NK cells in immune-based therapies.
Host Cell Signalling Following Coxsackievirus B3 Infection: Elucidation of Anti-Apoptotic Survival Mechanisms
Robert Yanagawa’s overall goal as a researcher is to increase our understanding of cardiovascular diseases. With that in mind Yanagawa is investigating Coxsackievirus B3, the primary cause of viral myocarditis (inflammation of the heart muscle), a condition that may result in chronic irregular heart beats, heart failure and sudden death. Organ transplantation is the only definitive treatment for heart failure caused by this virus. Yanagawa is examining the ability of host cells within infected cardiac muscle to activate protective signalling mechanisms. When stimulated, these mechanisms may maintain heart muscle viability, slow replication of the virus and preserve heart function. Yanagawa hopes that establishing new insights about protective mechanisms will ultimately lead to more effective treatments for viral myocarditis.