Although the average age of menopause is 51 years, approximately one per cent of women will experience menopause before the age of 40, a condition known as premature ovarian failure. Working on the hypothesis that multiple genetic factors may combine and interact in a single individual to determine the rate of reproductive aging, Karla Bretherick is examining the molecular genetic differences between women with normal reproductive function and women with premature ovarian failure. She hopes her work identifying specific genetic factors that contribute to early menopause may lead to the development of both treatment options for affected individuals and predictive testing for those at risk.
Tumour invasion is the cellular process that initiates the spread of cancer cells from the primary tumour to new sites in a patient’s body (metastasis). Inhibiting this process is important, as solid tumours are much more readily surgically removed if metastasis hasn’t yet occurred. Researchers have identified Dihydromotuporamine C (dhMotC) as a novel tumour invasion inhibitor that may have therapeutic potential. Lianne McHardy is investigating the molecular mechanisms of this compound, focusing specifically on how the protein SNF7 is involved in these mechanisms. SNF7 is normally required for the sorting of intracellular vesicles, which are a basic tool of the cell for organizing metabolism, transport, enzyme storage, as well as being chemical reaction chambers. Lianne will investigate a potential link between the mechanisms controlling vesicle sorting and the invasion abilities of a tumour cell. By pinpointing the mechanisms that allow for metastasis, her studies may aid in the development of dhMotC as a potential drug candidate for metastatic cancers.
Each year in Canada about 100,000 people develop sepsis—a severe illness caused by the presence of bacteria in the bloodstream. The condition causes blood pressure to drop, resulting in shock and may lead to multiple organ dysfunction and eventually death. With a mortality rate of 30 and 65 per cent respectively, sepsis and septic shock cause more deaths annually than heart attacks. Inflammation and immune response to infection varies greatly between patients. Some inflammation is a normal defense against infection. However, if inflammation is excessive, white blood cells and other cells can spill into the circulatory system and damage healthy organs. Continuing her previous MSFHR-funded research, Ainsley Sutherland is studying whether the genes that recognize bacteria and viruses play a role in determining which patients will develop the excessive inflammation that can lead to sepsis. This understanding could lead to the development of drug therapies for patients at higher risk of sepsis, and the avoidance of unnecessary drug side effects in patients who are not at risk.
Peptic ulcers affect approximately 3 to 5 per cent of the Canadian population. Helicobacter pylori (H. pylori)—a bacterium that causes chronic inflammation of the inner lining of the stomach—plays a key role in the development of peptic ulcers, chronic gastritis and gastric cancer. As H. pylori has been detected in water, drinking water may play a direct role in transmission of the bacterium. To date, minimal research has been conducted regarding the potential association between H. pylori infection and detailed water system characteristics, such as water source, treatment, well depth and aquifer. Neil Bellack is now conducting the first population-based research project that will examine the association between H. pylori infection and exposures to different water system characteristics, as well as other factors that may affect transmission of H. pylori such as sewage disposal methods and land use. Results from this study will identify the role that water systems and water quality play in the transmission of H. pylori, and point to potential mechanisms for blocking transmission of the bacterium and preventing infection.
Migraines affect about 15 per cent of the population, with the incidence being two times greater in women than in men. Symptoms of common migraines include pain, nausea, vomiting, sensitivity to light, sound, and smells, sleep disruption, and depression. Progress in developing new treatments has been slow due to a lack in understanding regarding the complex genetic roots of the disorder. Familial Hemiplegic Migraine (FHM) is a sub-type of common migraines with similar symptoms, but with simple genetic roots, making FHM a good model for study purposes. Most patients with FHM experience a visual aura – such as shimmering lights, wavy images or temporary vision loss – before the headache starts and varying degrees of paralysis in one side of the body (called hemiparesis). The symptoms can last from a few minutes to several days, in some cases outlasting the headache. About 50 per cent of patients with FHM have mutations in the CACNA1A gene. Paul Adams is investigating these mutations to better understand the molecular mechanisms that underlie migraines – an important step towards developing effective new treatments to alleviate all migraines.
Immune reactions in the central nervous system (CNS) – the brain and spinal cord – differ from other organs. Under normal conditions, the endothelial cells lining blood vessels in the brain act as a “blood-brain barrier” to block the entry of most immune cells into the CNS. In some CNS diseases like multiple sclerosis, and in trauma, stroke and infections, this barrier is compromised. As a result, immune cells migrate to the brain in large numbers causing inflammation, which can lead to serious consequences. Azadeh Arjmandi is studying how immune cells gain access to the brain and spinal cord in infectious, inflammatory and autoimmune diseases. Immune cells called dendritic cells have been found in the central nervous systems of patients with these diseases and their numbers increase with more chronic conditions. Azadeh is examining dendritic cell trafficking across the blood-brain barrier in order to further characterize the molecular mechanisms of inflammation in the brain. This will provide important information about how certain CNS diseases develop and may contribute to more effective treatments.
In the past two decades, researchers have examined how lung health is affected by changes in smoking and environmental and occupational exposures, and in the process have learned a great deal about the way lung disease develops. However, most of these studies focused on lung function tests rather than information on chest symptoms, even though detailed information on these symptoms has been collected in a questionnaire used around the world since 1978. A change in symptoms, not in lung function, is the most common reason people seek medical attention and express concerns about potentially harmful workplace exposures. Victoria Arrandale is examining data on changes in coughing, phlegm, wheezing and breathlessness to determine if unused data on these symptoms can help explain the development of chronic pulmonary disease, and contribute to disease prevention through occupational surveillance programs. The results could flag early signs that have been overlooked until now. Ultimately, the goal is to lessen the impact of occupational lung disease by controlling exposures and developing early methods of diagnosing disease onset.
Schizophrenia is a severe psychiatric illness affecting one percent of the general population. It typically begins in early adulthood and often has a devastating effect on an individual’s quality of life and functioning in society. The diverse and debilitating symptoms associated with schizophrenia include hallucinations, delusions, dampened emotion and poverty of speech. It has been hypothesized that faulty neuronal function may contribute to these symptoms. Communication between neurons is achieved by neurotransmission at synapses. Because soluble NSF-attachment receptor proteins (SNAREs) mediate this process, they are important in neuronal communication and normal brain function. Altered levels of SNAREs have been found in patients with schizophrenia, which may mean that abnormal levels of SNARE proteins disrupt normal transmission of synapses, contributing to the disorder. Vilte Barakauskas will compare SNARE protein levels from control subjects and from people with schizophrenia to identify differences in the brain. She will also attempt to identify the significance of SNARE properties in their role in neurotransmission. This information will increase our understanding of why brain function may be altered in people with schizophrenia. By comparing protein properties between control subjects and those with schizophrenia, Vilte is looking for molecular mechanisms that may contribute to altered neurotransmission. This may ultimately lead to new treatments for, and a better understanding of, this psychiatric disorder.
An important role of intestinal goblet cells is to secrete mucus into the gut, which is believed to act as a barrier, preventing contents in the intestine from damaging intestinal tissue. However, researchers have also hypothesized that mucus secretion by goblet cells may also serve as a defense mechanism against bacterial pathogens such as enterohemmorhagic E. coli (EHEC), a bacteria that causes diarrhea and inflammation in humans. Kirk Bergstrom is investigating if, and how, goblet cells may also secrete toxins to combat infecting microbes. With a better understanding of how these cells respond to bacterial pathogens, he hopes his research may lead to new treatment options to combat bacterial diseases of the intestine.
Vancouver’s Downtown Eastside community has the highest rates of HIV infection and the poorest health outcomes in Canada. Female sex workers in the community are among those at highest risk of infection. The limited success of public health programs and harm reduction interventions in this population reflect the multiple barriers that compromise their access to care. This includes socioeconomic factors such as poverty and unstable housing, the stigma associated with sex work, multiple addictions, and limited autonomy and personal choice. Disease control and harm reduction measures typically focus on individual responsibility, and often do not accommodate for the influences that can increase HIV risk and diminish autonomy among women in the downtown eastside. Susan Berkhout is utilizing an alternative framework developed from contemporary feminist and bioethics literature on ”relational autonomy” in order to more accurately characterize HIV risk behavior, and to produce more effective prevention and treatment strategies aimed at reducing HIV risk among female sex workers. This model considers the socioeconomic and cultural influences, and relationships involved in sex work and injection drug use. The findings should contribute to new harm reduction strategies tailored for this population, provide ethical guidance for researchers working with members of vulnerable populations, and help health care providers enhance autonomy in female sex workers.