In 1996, Dr. Gerald Krystal’s lab identified and cloned a protein named SHIP. Janet Kalesnikoff, a doctoral student studying with Krystal, is examining how SHIP regulates mast cell function. Mast cells are activated by a number of different antigens/allergens, which bind to IgE antibodies on the surface of mast cells. IgE-induced mast cell activation results in the release of chemicals (eg. histamine) which are responsible for the common symptoms of allergic reactions such as hay fever and asthma. Studies in Dr. Krystal’s lab have revealed that SHIP negatively regulates the process of mast cell activation. She hopes this research will ultimately increase the understanding of SHIP’s role in mast cell function and reveal way to reduce the symptoms associated with allergic disease.
Research Pillar: Biomedical
Structural Determinants of Kvl.5 Inactivation
Harley Kurata wants to contribute to the development of highly specific drugs with low toxicity for treating arrhythmia (irregular heartbeat). He’s focusing on potassium channels, the proteins that play a critically important role in regulating heartbeat. Because it is difficult to study potassium channels in isolated human heart cells, his research involves cloning genes to create these proteins in the laboratory. Kurata’s goal is to reveal how individual parts of the potassium channels are involved in regulating the channels’ function. He hopes the results can be applied to evaluation of current or potential anti-arrhythmia drugs. He also hopes that studying the effects of drugs on individual potassium channels will lead to new and more effective drugs to regulate irregular heartbeat.
Anticancer Drug Penetration into Solid Tumors
Solid tumours consist of a complex network of blood vessels surrounded by normal and malignant cells. They pose a particular challenge in the effort to develop anti-cancer drugs because malignant cell growth results in the development of regions in solid tumours that are resistant to radiation therapy. Anti-cancer drugs must overcome the barriers this environment poses, but there are currently no standard techniques for assessing a drug’s penetration in tumours. Alastair Kyle is addressing that gap by studying two techniques to examine the penetration of existing and new anti-cancer drugs. A better understanding of drug penetration in solid tumours could lead to the development of drugs that are more effective in entering the tumour. It could also lead to new insights into ways of modifying the tumour itself to make it more susceptible to specific cancer drugs.
Transgenic mouse models of congenital malignancies via expression of the ETV6-NTRK3 oncoprotein
During his Master’s research Christopher Lannon studied sensitivity to chemotherapy in adult and pediatric leukemias. Now Lannon is focusing on childhood cancers, which are biologically distinct from adult cancers and therefore present unique and interesting research challenges. He’s investigating a childhood tumour known as congenital fibrosarcoma (CFS). Several pediatric tumours, including CFS, are characterized by the fusion of two normal genes to form an abnormal fusion gene. Lannon aims to understand why this rearrangement of genetic material leads to malignant childhood tumours, with the goal of developing a mechanism to block the fusion.
Temperature Dependence of the Cardiac Sodium Calcium Exchanger
Mortality associated with open-heart surgery is two to three times higher in newborns than in adults. Christian Marshall believes this is due to a lack of knowledge about heart function in newborns, including how the neonatal heart responds to surgery. He’s focusing, in particular, on the inability of newborn heart cells to control calcium levels. When unregulated, calcium can initiate destructive events leading to cell death. Marshall is examining the effects of changes in temperature on the sodium-calcium exchanger (NCX), a protein in the heart cell membrane that is key to calcium regulation. Since surgeons need to reduce the temperature of the heart to perform open-heart surgery, and much of the cell damage occurs when warming the heart after surgery, Marshall is seeking a better understanding about temperature effects on NCX. He hopes this will reveal ways to reduce cell death during heart surgery and contribute to a better survival rate for these tiny patients.
The Role of the Rap1 GTPase in B Lymphocyte Migration and Adhesion
Sarah McLeod is examining the role of a protein, Rap 1 GTPase, in regulating essential cells in the immune system. In her previous research, McLeod discovered that this protein activates after B cells bind with antigens (substances that stimulate an immune response). Now McLeod is furthering that research by studying whether activation of the protein regulates the B cell activity, which enables the cells to produce antibodies for defense against harmful microbes and other infectious agents. Determining the overall function of Rap 1 in B cells and understanding how the protein regulates B cell adhesion and migration may provide insights into how these processes are regulated in B cells and other cell types.
Metabolism and Inactivation of Glucagon by Dipeptidyl Peptidase IV (DPIV)
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.
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.