More than 180 million people worldwide have either type 1 or type 2 diabetes. People with this condition are unable to maintain normal blood sugar levels due to a lack of, or insensitivity to, insulin, a hormone that regulates blood sugar levels. Whereas type 2 diabetes is usually caused by eating an unhealthy diet, type 1 diabetes is an autoimmune disease in which the affected personâs own immune system destroys the insulin-producing islet cells in the pancreas. Research shows that killer T cells (immune cells that normally attack virus-infected cells) cause type 1 diabetes by destroying islet cells. However, there has been little research completed to date regarding what causes T cells to attack the bodyâs cells. It has been hypothesized that sensors that recognize microbes like bacteria and viruses, called TLRs (toll-like receptors), may play a role. TLRs activate the immune system to fight off microbes; however, TLRs are also suspected of playing a role in the onset of type 1 diabetes. Andrew Lee is investigating whether a group of TLRs activate or accelerate the destruction of healthy cells in autoimmune diseases. Lee will also determine whether older, anti-malaria drugs and new designer DNA drugs can block these TLRs. Since symptoms of type 1 diabetes only appear when the pancreas is irreversibly damaged, this research could be used to identify people at risk of developing type 1 diabetes, and lead to new ways of preventing and treating the disease.
Program: Trainee
The role of the Rap1 GTPase in mediating the inflammatory and anti-microbial functions of macrophages
Large, white blood cells (called macrophages) play a crucial role in protecting the body against harmful viruses, bacteria and other substances, such as pollen, that the immune system recognizes as foreign. These cells trap the foreign substance and signal other cells in the immune system to start the inflammatory process needed to destroy them. Normally, the body tightly regulates the process ensuring that once the invader is destroyed, the inflammatory process is shut down to minimize damage to and promote healing in surrounding tissue. However, sometimes the process goes awry, such that the inflammatory process persists, which can lead to a variety of autoimmune diseases, including hay fever, atherosclerosis, and rheumatoid arthritis. Victor Lei is exploring whether a protein called Rap 1 is involved in activating the immune response to microbial infections by helping white blood cells find infected tissue and initiate inflammation. He is looking in particular to discover whether appropriate Rap1 levels create an effective response to infection, while excessive levels contribute to chronic inflammatory response that could lead to autoimmune diseases. The results of this research could help in the development of drugs that control Rap 1 activity to more effectively combat infections and prevent or minimize the chronic inflammation responsible for arthritis and other conditions.
Study of intercellular barrier alterations in enterocytes during Campylobacter jejuni pathogenesis
Campylobacter jejuni (Cj) is the leading cause of bacterial food poisoning in the world. Each year about 300,000 Canadians are infected by these highly invasive bacteria through ingestion of undercooked meats or dairy products. An acute infection causes diarrhea, fever, vomiting, and, occasionally, death. Cj infection may also lead to Guillain-Barré Syndrome, an autoimmune disease that causes weakness or tingling in the legs and arms. In some cases, symptoms can become so severe that the patient is almost totally paralyzed. Most people recover, although some continue to have some degree of weakness. Ann Lin is researching how Cj bacteria cause disease in the gastrointestinal tract. Cj is predominantly found in the first and last sections of the small intestine and the colon. The bacteria penetrate layers of cells in the intestine and infect underlying tissues. Lin is examining whether this process disrupts the intercellular junctions that provide integrity for host epithelial cells. Disrupting this barrier is believed to contribute to diarrhea, but the molecular process is not well understood. Lin will determine whether Cj causes gastrointestinal disease by damaging the barrier. Ultimately, her findings could lead to the development of new methods of preventing Cj infection.
Correlation Between Results from a New Magnetic Resonance Imaging Technique to Measure Myelin in the Spinal Cord and Somatosensory Evoked Potentials
Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool due to its ability to provide soft tissue contrast with high spatial resolution. Clinicians and researchers alike value MR images both for diagnosis and characterization of changes cause by disease. Recent advances have been made using MRI to image central nervous system white matter and investigate diseases that affect the white matter (such as Multiple Sclerosis), and damage to the spinal cord. The term âwhite matterâ is derived from the white colour of nerve tracts. It appears white because of the layers of fat wrapped around each nerve fibre, called the âmyelin sheathâ. If the myelin sheath has been degraded or broken down, transmission of information along the fibre can be slowed down or lost completely. In the case of a narrowing of the spinal canal, the invertebral discs slip out of place and put pressure on the spinal cord, damaging the white matter tracts, resulting in symptoms like a feeling of numbness or tingling in the hands or feet. Somatosensory evoked potentials (SSEP) are a current clinical tool used to detect myelin degradation and nerve damage in the spinal cord. However, SSEP measurements are limited to only sensory pathway nerves, and cannot locate damage throughout the entire spinal cord. The UBC MRI Research Group has recently developed an MRI technique to measure myelin content in vivo, termed âmyelin water imagingâ (MWI), which can be applied throughout the brain and spinal cord. Erin MacMillan is applying the MWI technique to healthy adults and people suffering from narrowing of the cervical spinal canal. She hopes to find that MWI provides results consistent with SSEP measurements in sensory pathways, and identifies myelin degradation throughout the cervical spine. In addition, she will compare patient results from before and after surgery in the hopes of finding that the white matter has been repaired. If MWI proves to be an accurate measurement of myelin in the spinal cord, it could potentially be used to track myelin content during new spinal cord injury treatments aimed at degrading myelin in an effort to encourage nerve fibre repair.
An examination of illicit drug use and sexual risk behaviours among a cohort of street-involved youth in Vancouver
Injection drug use has significant health consequences, including high rates of HIV and hepatitis C transmission. These problems have been exacerbated in recent years by the use of crystal methamphetamine (commonly called crystal meth), particularly in BC. Methamphetamine use is becoming increasingly common among marginalized youth, particularly those whose social and economic environment is the street. It is estimated there are between 45,000 to 150,000 street-involved youth in Canada, most of whom live in the large urban centres of Toronto, Montreal and Vancouver. Illicit drug use and unsafe sexual practices, including unprotected sex and sex trade work, increase susceptibility to HIV infection among street-involved youth. Brandon Marshall is one of the few researchers investigating the relationship between illicit drug use and sexual risk behaviours among street-involved youth. Using data collected from the B.C. Centre for Excellence in HIV/AIDS At-Risk Youth Study, he will examine how different social, structural, and environmental factors impact sexual practices. Specific factors include the age of first sexual experience, sexual orientation, illicit drug use, sexual relationships with older partners, access to health services, and involvement in the Downtown Eastside community of Vancouver, where drug use and poverty are prominent. This research will improve our understanding of illicit drug use and sexual activity in marginalized youth and will play an important role in developing sexual health education and prevention programs for youth at-risk.
Characterization of a kinase implicated in kinetochore function during S phase
Chromosomes, which are a compacted form of DNA, must be accurately duplicated and separated into two new daughter cells during each cell cycle. Genetic instability arises when chromosomes are separated improperly. This error is the source of many diseases, such as cancer and Downâs syndrome. Accurate chromosome separation relies on machinery assembled on each chromosome called the kinetochore. The regulation of the kinteochore is essential for cellular fitness and prevention of genetic instability. Understanding the mechanism by which the kinetochore is regulated will lead to a better view of cellular division and will provide insight into the treatment of diseases such as cancer. Because chromosome separation is a fundamental cellular process in all types of cells, Jennifer McQueen is using budding yeast as a model to study chromosome segregation. She is using many genetic and biochemical tools to examine the involvement of the Mck1 kinase in chromosome separation. Her project aims to discover a new role for the Mck1 kinase in kinetochore function and to produce a new model of kinteochore regulation that is applicable to human health.
The biological role of bone marrow-derived keratinocyte precursor cells in wound healing
Skin, which is the most extensive organ in the human body, performs multiple vital functions. Wounds to this organ, whether chronic or acute, are a serious threat because they leave the body open to infection. Thatâs why burns are a major cause of infection-associated deaths and why early replacement of burned tissues is so critically important. There is an urgent need to engineer skin substitutes for patients with extensive burns who do not have enough skin available for harvesting as grafts to close wounds. However, relatively little is known about how to establish a large-scale production of skin substitutes and how to control the healing process when such material is used. Bone marrow-derived stem cells may be a potential source for the preparation of skin substitutes due to their capacity to be reprogrammed to produce a variety of cell types. Abelardo Medina is studying whether bone marrow-derived stem cells can be used in this fashion both to close wounds and to improve wound healing. Findings from his research may also lead to a better understanding of the healing process and the treatment of chronic non-healing ulcers that develop in elderly people, diabetic and immuno-compromised patients. It also may contribute to a better understanding of the processes associated with over-healing wounds such as those that result in thick burn scars.
Use of a recombinant fusion protein to expand hematopoietic stem cells in vitro and to elucidate mechanisms that determine the expansion and self-renewal potential of mouse fetal liver and adult stem âŠ
Bone marrow is the tissue that fills most bone cavities and is the source of red blood cells and many white blood cells. Disorders that require bone marrow transplantation include aplastic anemia (inadequate blood cell formation by bone marrow), immune disorders, and many types of blood cancers. Current bone marrow transplantation therapies are limited by the number of blood-forming hematopoietic stem cells (HSC) that can be isolated from the patient or donor and transplanted to the patient. Typically, bone marrow or peripheral blood, as closely matched as possible to the patient, is transplanted into the patient. As this match is rarely perfect, patients will often develop a condition of varying severity known as graft-versus-host disease, which causes the patientâs immune system to destroy donor cells. Michelle Miller aims to generate in the laboratory a non-viral method of expanding HSC in the aim of avoiding certain complications that can arise from gene therapy or allogenic bone marrow transplantation.. Michelle (or Ms. Miller) is in the process of testing a fusion protein, which in viral form, has proven to lead to significant HSC expansion and generation of functional mature cells without leading to malignancy. She is also investigating whether there are pathways in common between the self-renewal capacity of mouse fetal liver HSC and those found in the adult as these cells perform better in transplantation tests when compared to HSC from adults. Ms. Miller (or Michelle â see above)hopes her research will lead to increased knowledge about hematopoietic stem cells, and to safer, more effective stem cell therapies.
Impact of community engaged arts on the health status of older adults
With the number of seniors in Canadaâs population increasing, more older adults are potentially dealing with chronic or recurring health issues. Given this trend, thereâs an essential need to identify health resources available to these individuals and to evaluate the effectiveness of these resources in impacting health status. Recent research has show that that creative involvement in the arts positively impacts the health of older adults. Elaine Moody is investigating how a community-based art project impacts health among its older adult participants. She is studying groups of seniors in the Vancouver area who are currently participating in community-engaged arts projects focused on developing creative and artistic abilities, and providing opportunities to meaningfully contribute to their communities. Through a questionnaire and a series of interviews, Elaine is collecting information about the health status of the participants, including physical, mental and social health, and overall well-being. Using statistical methods, she is examining the information obtained to determine if health status has improved over the course of the study. Her overall aim is to provide a clearer understanding of the health benefits of participating in community engaged arts for older adults.
Modulation of Cav3.2 T-type calcium channels through neuronal nitric oxide synthase activity
Normal brain activity involves the controlled transmission of electrical impulses across networks of neurons (nerve cells). Occasionally, undesired electrical activity occurs within cellular networks and a response is necessary to suppress this outburst. Kirk Mulatz is investigating a negative feedback mechanism that allows neurons to inhibit this atypical electrical activity. He is focusing on the role of T-type calcium ion channels in generating this aberrant electrical activity, and exploring the effectiveness of inhibiting characteristics of the channels to inhibit the activity. Investigations into negative feedback mechanisms both increase understanding of normal brain activity and how cells respond to abnormal activity. A number of neuronal disorders such as epilepsies, mood disorders and chronic pain are associated with atypical brain activity, and the feedback mechanism that Mulatz is researching may contribute to restoring normal activity across cellular networks.