Research Location: University of British Columbia - Point Grey

Stroke is one of the leading causes of death in North America affecting about 16,000 Canadians each year. This disease causes a sudden loss of blood to an area of the brain typically due to blocked or ruptured blood vessels. Michael Kozoriz is studying how to reduce brain damage caused by stroke. The brain has two classes of cells – nerve cells (neurons) and glial cells. Neurons conduct electrical impulses, while glia surround, support and protect neurons. Glia are the most abundant cells in the central nervous system and are connected by a junction made of a protein called connexin43. Because these cells are physically attached they have the ability to share various molecules and nutrients. Studies have shown that stroke damage is less severe in the presence of connexin43, and damage is greater if the protein is absent. Michael is examining how connexin43 protects cells from death. He suspects the junctions remain open during a stroke, allowing neighbouring cells to share nutrients, much like neighbours helping a friend in need. His findings could explain how to protect the brain during stroke, and ultimately, lead to better treatments for this disease.

The molecules that are essential for normal brain functions are transported throughout neurons, travelling from the site of their formation to the specific location where they are activated. Defects in the transport and exchange of these molecules may affect brain activity and lead to neurological impairments such as epilepsy and mental retardation. Marie-France Lise is studying Myosin V, a family of proteins that may be important regulators of how molecules travel across neurons and reach their destinations. By characterizing how the Myosin V family regulates transport, she hopes to create a better understanding of how these processes contribute to essential brain development, learning and memory formation.

Aneuploidy – the result of the uneven separation of two matching sets of chromosomes during cell division – is found in more than 70 per cent of cancers and is now widely accepted as a major predisposing condition to cancer initiation and progression. Benjamen Montpetit is studying the role of the kinetochore, a protein complex that is of fundamental importance to the equal separation of chromosomes during cell division. Using yeast cells as a model, his research into the components responsible for chromosome transmission will result in a better understanding of the events involved in creating aneuploid cells and will provide a mechanistic basis for understanding chromsome instability in human cancers.

Disease states such as Alzheimer’s, Parkinson’s, stroke and spinal cord injury each affect the nervous system in what was once thought to be an irreversible manner. However, recent scientific evidence suggests that damaged areas of the nervous system may have their functions restored by transplantation of neural stem cells or by administration of molecules that coax the body’s neural stem cells to self-repair. To put this knowledge into practice, researchers require a better understanding of the basic mechanisms of stem cell development. Barbara Murdoch was previously funded by MSFHR to identify proteins specific to the surface of neural stem cells so she can study their growth requirements. Building on this, she is now using olfactory epithelium cells to determine the role of the protein nestin in the development of neural stem cells. She is studying which cell types express (produce) nestin and determining their pattern of expression. By understanding these mechanisms, she hopes to contribute key knowledge necessary for effective clinical applications requiring stem cell transplantation, expansion and gene or drug therapies.

Cardiovascular complications are the major cause of morbidity and mortality in diabetes – a disease that affects millions of people worldwide. The lack of specific treatments for these complications is due, in part, to the poor understanding of the underlying cellular and molecular mechanisms, e.g., the signalling pathways that might cause malfunction, and pathways that protect normal vascular function. In diabetes, there are changes in the ability of blood vessels to constrict and relax, which in turn can affect blood flow and blood pressure. Prabhakara Nagareddy is studying how blood vessels function in diabetes and the mechanisms directly relevant to the development of vascular disease. He is exploring the vasoconstrictory role of a well-known growth receptor (epidermal growth factor receptor) pathway and the vasodilatory inducible nitric oxide synthase (iNOS) pathway in normal and diabetic arteries. By developing an understanding of how these pathways produce their effects, this research could facilitate the discovery of unique drug targets for future cardiovascular disease treatments, particularly for high blood pressure.

Pregnancy and motherhood are life-changing events that often result in cognitive and mood disturbances. Research has shown decreased verbal recall and decreased spatial ability in women during the last trimester of pregnancy. Spatial memory relies in part on the integrity of the hippocampus in the brain, and on the steroid hormone corticosterone, but little is known about the effect of pregnancy and motherhood on these processes and how they relate to memory and learning. Jodi Pawluski is investigating the relationship between corticosterone, hippocampus structure and hippocampus-mediated learning and memory during pregnancy and motherhood. In addition to advancing understanding of how reproductive experience affects neurological, cognitive and hormonal processes in the mother, she hopes her work may contribute to the development of therapies for pregnancy-related diseases such as postpartum depression.