Huntington disease (HD) is an inherited, neurodegenerative disease characterized by loss of motor control and cognitive decline, eventually leading to death. Elizabeth Slow is studying atrophy and cell loss in the striatum, the most affected region of the brain, and the motor dysfunction associated with HD. A group of proteins called caspases split other proteins, including huntingtin, the protein produced by the HD gene. In collaboration with researchers at Harvard, the University of California and the Buck Institute in California, Elizabeth is investigating whether this process triggers inappropriate cell suicide in the neurons affected by HD, thus causing the disease. If so, the results will determine whether caspase inhibitors are an effective treatment option for people with Huntington disease, which currently has no treatments to prevent or delay the condition.
Program: Trainee
Model Membrane studies of Amphotericin B's mechanism of action (towards less toxic AmB formulations and new tools for drug/membrane studies)
Amphotericin B (AmB) is an antifungal antibiotic used to treat infections in patients with depressed immune systems, such as cancer patients, organ donor recipients, diabetics and people with AIDS. Fungal infections are thought to account for up to 30 per cent of deaths among these patients. Although effective, use of AmB is limited because it can also cause kidney toxicity. AmB is known to interact with parts of the cell membrane, forming pores that allow leakage and ultimately cause cell death, but this process is poorly understood. Robin Stoodley is researching how the drug interacts with the body at the cellular and molecular levels, with the goal of finding ways to reformulate AmB to reduce its toxicity and improve effectiveness. The techniques Robin develops for this research may also be used to study chemotherapy and other drugs, leading to the development of better drug therapies.
Pathogenesis of confined placental mosaicism (CMP) during pregnancy
The frequency of chromosomal abnormalities in reproduction is significant — 15 to 20 per cent of all pregnancies end in spontaneous abortion, and half of these miscarriages are associated with chromosomal abnormalities. In 1983, two UBC professors discovered a condition now known as confined placental mosaicism (CPM), where a chromosomal abnormality is present in the placenta but not the fetus. CPM allows a pregnancy that would otherwise spontaneously abort to continue to term, and is present in at least two per cent of pregnancies. In his earlier research, Paul Yong confirmed that some types of CPM increase the risk for poor fetal outcomes such as low birth weight or complications such as pre-eclampsia. Now he is studying how chromosomal abnormalities cause alterations in placental structure and function. The hope is to identify potential therapeutic interventions in pregnancies affected by chromosome abnormalities in the placenta.
Development of a direct computer interface using descending motor potentials recorded from the spinal cord
A variety of devices are available for individuals with motor impairments, such as electrical stimulation systems for locomotion. But people with severe disabilities are often unable to control these devices effectively. Dr. Jaimie Borisoff, who has published research papers on neural regeneration in the journals Experimental Neurology and Molecular and Cellular Neuroscience, is researching assistive technologies to enhance quality of life for people with severe disabilities. Jaimie is investigating whether motor control information can be recorded directly from the spinal cord, since much of the intentional and logistical processing has already been performed in the brain before the signal pathway terminates at the spinal lesion. If so, this information could be used to create a control system that uses signals from the spinal cord.
Gap Junctional Hemichannels in Astrocytes: Regulation in Normal and Injured CNS
Gap junctions are connections between cells that allow free passage of ions and small molecules. Because ions can flow through them, gap junctions permit changes in membrane potential to pass from cell to cell in most body organs, including the brain. Gap junctions are key elements in cellular communication that are essential for normal embryonic development and function in adult organs. Combining his engineering background with more recent training in biochemical research, Dr. Francisco Cayabyab is using a number of research methods to investigate deficient levels of gap junctions and examine their regulation and function. He hopes this research will contribute to the development of new therapeutic strategies targeting gap junction proteins for certain neurological disorders, including stroke, epilepsy and schizophrenia.
Molecular mechanisms of SP12-mediated virulence in Salmonella Typhimurim
Salmonella enterica serovar Typhimurium is a bacterium that causes gastroenteritis, a type of food poisoning characterized by abdominal pain, fever, vomiting, and diarrhoea. Most Salmonella infections arise from oral ingestion of tainted food or water and are a significant cause of disease and death in animals and humans worldwide. Dr. Brian Coombes is studying the molecular mechanisms by which Salmonella use virulence factors to modify their host environment. Once injected into mammalian host cells, these virulence factors rearrange and reprogram the cells so that Salmonella can replicate and evade the body’s immune system. Learning more about how bacteria use specific virulence factors to manipulate their environment during infection may lead to the design of new therapeutic strategies to treat or block the disease process.
Mechanisms of pathogenic E. coli – host cell interactions
Escherichia coli (E. coli) bacteria cause numerous diseases including meningitis, urinary tract infections and diarrhea. Worldwide, enteropathogenic E. coli (EPEC) is one of the leading causes of diarrhea in children and is an endemic health threat in the developing world, causing the death of several hundred thousand people each year. Isolated outbreaks of enterohaemorrhagic E. coli (EHEC) also occur in developed countries, often transmitted in contaminated hamburgers and water supplies, and can cause diarrhea and fatal kidney disease. After binding to the cells that line the intestine, E. coli injects several proteins that lead to diarrhea and disease. Dr. Philip Hardwidge aims to identify these proteins and determine their structure and function. He is also examining how intestinal cells respond to E. coli at the level of gene expression, using an advanced technique to analyze several thousand genes at a time. This research could guide the design of future vaccines and antibiotics to prevent and treat E. coli.
Molecular mechanism linking Hox transcription factors to leukemia
Leukemia affects one to two per cent of the population in the industrialized world. The disease occurs when the genes that control the normal process of blood cell formation function abnormally, and bone marrow produces malignant white blood cells as a result. These cancerous cells accumulate, interfere with the body’s production of healthy blood cells, and make the body unable to protect itself against infections. A family of genes called Hox genes are present in elevated levels in patients with some forms of leukemia, and are known to play a crucial role in the disease. Dr. Koichi Hirose is investigating the molecular function of these genes to explain how they transform normal blood cell development into leukemia. His research could help in the development of new therapies for treating Hox-related leukemia.
Bioinformatic analysis of large-scale microarry data
Dr. Karsten Hokamp is already known for developing the PubCrawler service used worldwide to stay up to date with the medical literature database PubMed. Now he is working on a large-scale project comprising databases and tools to support genetic research into immune responses against viral and bacterial infections. As part of a major Genome Canada project, laboratories across Canada are studying genetic information on viral, bacterial and fungal infections that affect humans and animals. Researchers are using microarray technology to simultaneously examine thousands of genes. Karsten’s platform will be capable of storing and processing what may possibly be the largest set of microarray data ever generated in Canada. He will set up a system to collect and analyze the data, with capability of comparing genetic information from different organisms and species. This system will contribute to improved understanding of immune responses and will aid in developing new ways to prevent and treat infections in humans and animals. In addition, other institutions worldwide that are increasing production of microarray data could use this setup as a model.
The value of cardiac specific troponin in predicting cardiac outcomes in an asymptomatic chronic kidney disease population
Chronic kidney disease is associated with a high risk for heart attack, even after accounting for traditional cardiac risk factors such as smoking and high cholesterol. The risk increases as kidney function deteriorates. Elevated levels of a cardiac enzyme called cardiac specific troponin (cTn) have been shown to predict heart attack or death in people with acute coronary conditions. Some studies also suggest that elevated cTn can predict cardiac outcomes in patients with chronic kidney disease who do not present cardiac risk factors. Nadia Khan is researching whether elevated levels of cTn can be used to accurately predict heart attack and death in patients with different levels of chronic kidney disease. The results could help clinicians identify patients with chronic kidney disease who are at high risk of heart disease, and also provide the foundation for developing therapies that prevent cardiac disability and death in this patient population.