The Hereditary Cancer Program at the BC Cancer Agency provides genetic testing and counseling services. The demand for these services in BC depends on many factors, each of which is subject to change. Factors include the growing knowledge in basic, applied and social sciences relating to hereditary cancer; the size of BC’s population and its characteristics in terms of age, ethnicity and family size; the evolving criteria by which people are deemed eligible for services; and people’s desire for these services. Through his research, Dr. Chris Bajdik is determining the demand for hereditary cancer services in BC and predicting how this demand may change in the future. He has created a computerized simulation model of the BC population, based on information about demography, cancer epidemiology and etiology, genetics, genetic technology, and human behaviour. The results from this model will help the BC Cancer Agency plan its services and assess the health benefits and costs of its Hereditary Cancer Program.
Research Location: BC Cancer Agency - Vancouver
Identification of Notch4-Modulated Genes in Vascular endothelia Cells
Graeme McLean’s research focuses on angiogenesis, the process by which a person’s existing blood vessels sprout extensions from themselves to enhance blood flow or nutrient delivery. The process is critical in embryo development, wound healing and inflammation. Defects in angiogenesis can interfere with wound healing and contribute to conditions such as rheumatoid arthritis. Abnormal patterns of angiogenesis also contribute to the growth of cancerous tumours that are capable of co-opting the process to increase their blood supply. In addition, the ability to increase blood flow to the heart is crucial to the survival of heart attack victims. McLean is studying Notch4, a protein in endothelial cells that line the blood vessel wall and participates in the regulation of angiogenesis. Investigating how this protein works will lead to a better understanding of angiogenesis and provide insights into correcting defects in the process.
Genetic analysis of natural killer cell functions
Linnea Veinotte believes immunology (studying the immune system’s functions and disorders) and molecular genetics (studying the molecular structure and function of genes) will be an important research combination in the future. Linnea worked in both areas during her Master’s Research, studying natural killer (NK) cells, unique types of lymphocytes (white blood cells). Distributed in various tissues, the cells are thought to be the body’s first line of natural defense against cancers and viruses. NK cells can kill a wide range of cancer and virus-infected cells but not normal cells. Linnea aimed to better understand their development during varying stages. Linnea discovered, unexpectedly, that a small percentage of NK cells in the neonatal and adult stage express a gene specific to T cells: the T cell receptor gamma gene (TCR). This suggests that a population of NK cells shares extensive characteristics with T cell development, and that multiple developmental pathways of of NK cells may exist. She continues to further define NK cell differentiation in her PhD program, and hopes that the research will contribute to treatments for cancer and virus infection.
Role of complement in the antitumor effect of photodynamic therapy and its exploitation for therapeutic gain
Ivana Cecic is investigating a novel strategy in the fight against cancer. Her research concerns the complement system, a series of proteins that help the body protect itself from harm due to infection and injury. During the course of certain diseases, such as heart attack and stroke, complement activates against tissues and can result in life-threatening consequences. Cecic conducted research that revealed complement contributes to the effectiveness of photodynamic therapy, a new method of activating light-sensitive drugs in specific tissues as part of the treatment of a variety of cancerous and non-cancerous lesions. Now she’s examining the potential of harnessing complement’s tissue-destructive power in cancer treatment involving photodynamic therapy. Cecic hopes the research will contribute to more effective treatment of malignant tumours.
The Role of Homeobox Transcription Factors in Hematopoietic Stem Cell Function
For her Master’s research, Rhonna Gurevich studied the prevention of apoptosis (programmed cell death) in cardiac cells. Now she’s examining the genes that transform normal blood cells into malignant ones in leukemia patients. Gurevich is focusing on hematopoietic stem cells, which can self-renew to produce more stem cells with non-specific function or divide to create highly specialized cells to replace others that die or are lost. Maintaining the balance between stem cell self-renewal and division is a tightly controlled process. Gurevich is investigating how certain genes regulate hematopoietic stem cells, and specifically, how they may cause leukemia by disrupting the normal balance of cell renewal and division. She hopes that increasing knowledge of these genetic alterations can enable development of drugs to treat and potentially cure leukemia patients.
The characterization of bone marrow-derived mast cells (BMMCs) from SH2-containing inositol 5'-phosphatase (SHIP) knock-out mice
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.
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.
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.
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.
Mechanisms and functions of activin/nodal signaling in early embryogenesis
We all start as a single cell, which divides and eventually forms the body. A great deal of cell communication goes into making decisions about this body plan. My research examines how cells communicate with one another during embryonic development. The body plan is set up by organizing centres, or groups of cells that dictate signals to other parts of the early embryo. Two centres have been identified in mammals: the anterior visceral endoderm (AVE) coordinates the development of the head, and the node arranges the trunk into front, back, left and right. The way these organizing centres control growth of the embryo, and the cell-to-cell signalling involved in the process, are poorly understood. The same signalling systems used in creating an embryo break down during cancer. Ultimately, if we can identify what happens under normal circumstances, we can better understand what goes wrong with signalling pathways during the development of cancer or congenital defects. The results of my research also have implications for stem cell research. Stem cells have the potential to differentiate into various types of cells. If we can determine the signals that cause particular cells to become liver, brain or kidney cells during embryonic development, researchers should be able to cue stem cells to differentiate into specific cell types.