Cystic fibrosis (CF) is a severe genetic disorder caused by one gene: the cystic fibrosis transmembrane regulator gene (CFTR). Inheriting the gene from both parents leads to CF. People with CF experience chronic respiratory infections that cause lung damage and ultimately lead to lung failure and death. Lung damage in CF is not fully understood and cannot be completely explained by the CFTR gene defect. There are considerable differences in the severity and progression of lung disease, for example, among patients with the same mutation in the CF gene. Some may require lung transplantation by their teenage years, while others may not experience severe lung disease until adulthood. Daisy Frangolias is looking specifically at two types of genes: ones that are involved in fighting lung infections, and those that are involved in initiating and controlling the inflammatory response to the bacteria that cause lung infections. Her findings will increase the understanding of the relationship between the CF gene disorder and other genes in defining the long-term progression of CF, and may provide therapeutic targets for reducing lung damage.
Year: 2002
Phylogeny of the Ichthyosporea
The Ichthyosporea are a group of single-celled parasites that infect a variety of animals, including humans. The group has only very recently been identified on the basis of some preliminary genetic data, and appears to have evolved from animals and fungi. Very little is known about these parasites, and genetic data is needed to understand their evolution and how they function. Audrey de Koning is determining the DNA sequences of some common genes in several Ichthyosporeans and comparing these sequences to the genes of other organisms. This will allow her to identify similar genetic patterns and learn more about how Ichthyosporeans evolved. She is also generating a large number of DNA sequences for expressed genes-genes that have had their coded information converted into the structures present and operating in a cell-in a representative member of the Ichthyosporea. This will give a broad picture of how these parasites function, and may uncover weaknesses that can be exploited to develop new disease treatments.
Contribution of granzyme B-induced cell death to atherosclerotic plaque rupture
Jonathan Choy brings previous research experience in the mechanisms of controlled cell death to his work at the Cardiovascular Research Laboratory in the McDonald Research Laboratories at St. Paul’s Hospital. His research focuses on atherosclerotic plaques in the vascular system—also known as hardening of the arteries—caused by a buildup of lipids on the innermost portion of the arteries. Advanced plaques tend to break down and rupture, and can lead to blood clots and heart attack. Jonathan is specifically studying the role of granzyme B—a protein normally used by the immune system to kill abnormal and infected cells—in causing plaque rupture. He is investigating whether granzyme B destroys structural cells in the plaques, thereby reducing the integrity of this part of the vessel wall. Understanding the processes that alter the structural integrity of the atherosclerotic plaques could enable control of some of the events that lead to heart attacks.
Abnormal response to vasoactive agents in pulmonary hypertension
Pulmonary hypertension (PHT) is a life-threatening disease; people with PHT experience shortness of breath, chest pain and fainting and live an average of 2.5 years after diagnosis. The disease involves increased production of endothelins in the lungs, which constrict blood vessels in the lungs. Endothelin is a potent vasoconstrictor (constrictor of blood vessels). Xing Cheng is investigating how certain substances produced in the lungs with PHT influence the ability of endothelin to constrict blood vessels. She is also examining how anti-inflammatory drugs that inhibit the formation of these substances affect production of endothelin. Her research will help identify drug combinations that may reverse the cardiovascular abnormalities causing pulmonary hypertension.
Molecular mechanisms that control CD 44 mediated binding to hyaluronan in monocytes
White blood cells are the key elements of the immune system that keep our bodies healthy. Normally these cells circulate in the bloodstream, but upon infection or injury, the cells exit from blood vessels and enter the damaged tissue to promote healing. Proteins on the cell surface, called cell adhesion molecules, take white blood cells to the afflicted site. These molecules are tightly regulated to ensure they only allow cell migration into damaged tissues. When regulation fails, cell adhesion molecules may promote inflammatory diseases such as arthritis, inflammatory bowel disease and atherosclerosis or metastasis (transfer from one organ or body part to another) of cancer. Kelly Brown is studying CD44, a cell adhesion molecule found in mice and humans on virtually all cell types. Kelly is investigating CD44 on particular white blood cells called monocytes. Once in damaged tissues, these cells eliminate pathogens and alert the rest of the immune system. She is examining the changes that occur in CD44 when monocytes are activated and how the regulation of CD44 contributes to monocyte function during an inflammatory response. Kelly ultimately hopes to learn how to block or promote CD44, which could lead to new treatments for inflammatory diseases and cancer.
Conditioned effects in the kindling model of epilepsy
Mild electrical stimulation of various brain sites leads to the development of seizures, which intensify over time. Called the kindling phenomenon, this process has been widely studied as a model of epilepsy, neuroplasticity (learning, memory and various mental disorders) and the interictal (emotional) changes that occur between seizures in certain types of epilepsy. In his previous research, Steven Barnes demonstrated that learning plays a major role in this process. His studies show that rats learn to associate particular environments with seizures and this awareness greatly affects the intensity of seizures and interictal behaviours. People with epilepsy also tend to have more seizures in certain situations than others, a pattern that has not been widely studied. Steven is investigating how conditioning affects these responses. His research will ultimately reveal insights about the role of conditioning in the kindling phenomenon associated with epilepsy.
Parent-child interactions in families of children with Attention Deficit Hyperactivity Disorder
Approximately four percent of children in elementary schools suffer from Attention Deficit Hyperactivity Disorder (ADHD). This disorder places children at an increased risk for developing problems such as antisocial behaviour, substance abuse and career difficulties. Carla Seipp is examining whether parents’ responsiveness to a child may be an important influence on the risks and impairments associated with ADHD. Carla will compare responsiveness during interactions between mothers and sons with ADHD, and mothers and sons with no behavioural difficulties. By focusing on the family environments of children with ADHD, Carla hopes to identify parenting behaviours that could reduce the risks and impairments associated with the disorder.
Therapeutic existential experiences during wilderness exposure: Implications for wilderness therapy programs
Mark Ring already holds a PhD in Biochemistry, but his focus shifted recently to work on a degree in the social sciences. He is now researching the therapeutic benefits of exposure to wilderness. Wilderness therapy has been used to help at-risk groups, such as people with mental illness, adolescent alcohol and drug users, adult female survivors of sexual abuse, and war veterans suffering from post-traumatic stress disorder. Programs vary greatly, but include some outdoor adventure activity, from wilderness day trips to three-week hiking and kayaking expeditions. Most research has measured the positive impact of wilderness therapy on self-esteem and ability to interact socially. But participants’ first-hand reports suggest a deeper healing process occurs. Mark is interviewing participants to determine how this experience helps people adapt, live more fully, and find greater meaning in life. He hopes this information can help make wilderness programs more effective at improving participants’ emotional and mental health.
Chemical high-level disinfection in acute care
Most hospital equipment is sterilized by heat or steam after use. But some types of equipment cannot be heat sterilized and must be disinfected using chemical products, which potentially could place employee health at risk. Karen Rideout is surveying BC hospitals and health care centres to assess current practices for using these chemicals. She is focusing on Glutaraldeyde, the most widely used solution in Canadian hospitals to disinfect endoscopy, bronchoscopy, ultrasound, and other equipment. Karen is also examining several new products to assess potential health effects and evaluate whether or not protective measures could reduce these effects. She plans to use this information to develop guidelines for use of disinfectant products, with the goal of making health care environments healthier.
Role of PI3-kinase family in phagocytosis and phagosome maturation
Successful host defense against microorganisms relies heavily upon a population of immune cells called macrophages. These cells are capable of ingesting and destroying pathogens such as bacteria and yeasts. Jimmy Lee’s research will investigate the cellular mechanisms involved when macrophages ingest and destroy pathogens. Specifically, he is studying a protein family called PI(3)K, which is responsible for activating many cellular activities and is believed to enable macrophages to ingest microorganisms. He aims to identify the specific PI(3)K protein involved in this process. This research will increase the understanding of how the body responds to infection and may lead to the design of specific therapeutic approaches to fight infections.