Some carbohydrates act as a “fingerprint” or marker for each cell. These markers allow cells to recognize and talk to each other, which is critical for all aspects of cell development and cell-to-cell interaction. Importantly, carbohydrate markers allow the body to discriminate between substances that belong to the body from those that are foreign in order to determine the appropriate immune response required. Further protection against foreign material is provided by protective layers of mucus at entry points to the body such as the nose, throat and lungs. These layers are derived from carbohydrates. Many disease-causing bacteria are able to attach to, and infect cells, by binding to these carbohydrates. Alicia Lammerts van Bueren is studying how enzymes called glycoside hydrolases enable bacteria to infect human cells and hide from the body’s immune system. Her specific focus is on a glycoside hydrolase found on the surface of both Streptococcus pneumonie, which is the leading cause of pneumonia and bacterial meningitis, and Streptococcus pyogenes, which causes strep throat, necrotizing fasciitis and toxic shock. All these diseases can be fatal if left untreated. Alicia’s research into the carbohydrate binding function of these enzymes may explain how these bacteria cause disease in humans, and potentially lead to new drugs or vaccines to treat bacterial infections, which is particularly important given the rise of antibiotic resistance to streptococcal infections.
Year: 2006
Risk Assesment for Oral Cancer Prevention in the Community
Even in countries with the best survival rates, 40-50 per cent of patients with cancer of the mouth (oral cancers) do not survive five years beyond diagnosis and treatment. Late diagnosis plays a major role in this high mortality rate because oral lesions at high risk of progressing to cancer are often difficult to differentiate from lesions that are a result of trauma or infection. Denise Laronde is examining two components central to the development of an effective oral cancer screening program. She is identifying and validating tools that can be used by dental professionals to help identify which oral lesions require follow-up. She is also designing and implementing a pilot education program for dental professionals to help train them in the use of these devices. Transferring this new technology to the community may result in earlier identification of high-risk lesions, and increasing the potential for earlier treatment and ultimately, improved long-term survival.
Characterization and Thrombogenic Contribution of Platelet Microparticles to Pathogenesis of Transient Cerebral Ischemic Attacks and Unstable Angina
Platelets are cells that augment blood coagulation to form blood clots which in some cases can restrict or halt oxygenated blood flow to the heart and the brain, causing a heart attack or stroke. Although drugs like aspirin have an anticoagulant effect that can decrease the chance and severity of a stroke or heart attack, these drugs do not entirely eliminate the risk. Platelets release mini-versions of themselves, called platelet microparticles (PMPs), into circulation, which are not affected by anti-coagulant drugs. The presence of PMPs in blood is a predictor of future blockages in the brain or heart, but their precise role is not clear. Hon Leong is investigating whether PMPs have the same clotting abilities as platelets to determine whether they cause the blood clots that lead to a stroke or heart attack. Hon is examining the structure of platelet microparticles and their ability to bind to other cells and clots. The results potentially may be used to develop more accurate blood tests to predict and detect strokes and heart attacks and, ultimately, new therapies that prevent platelets and PMPs from producing harmful clots.
Involvement of myosin V in glutamate receptor trafficking in neurons
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.
Elucidating the role of Fa2p in cilliary and cell cycle regulation
The majority of cells in the body contain a microscopic, hair-like organelle projecting from the cell surface called a cilium. Cilia play roles in motility and sensory signalling. In many cells, the disassembly of cilia by the cell is a precursor to mitosis (cell division) and cilia are reassembled by the cell following mitosis. Dysfunction of this structure and process leads to a variety of conditions, including blindness, infertility and polycystic kidney disease. MSFHR funded Moe Mahjoub in 2003 to complete his PhD study of cilia. His previous work showed that the kinase Fa2p is implicated in the regulation of ciliary shedding and assembly, as well as in cell division. He has determined that Fa2p is dynamic, moving to different locations in the cell at different points in the ciliary and cell life cycle. Moe is now working to discover exactly how Fa2p exerts its effects. He hopes his research will provide key insights into the mechanism of various human diseases.
Bayesian propensity score analysis for pharmacoepidemiologic research
Data on prescription claims, health services provided, and hospital discharges are routinely collected in the Canadian health care system for the management of health services. This information is valuable for observational research assessing the effectiveness and safety of drug therapies, allowing more rapid and cost-effective investigations. In addition to yielding large sample sizes with long periods of follow up, they also better reflect the spectrum of medical practice in large populations compared to randomized clinical trials. However, because study participants are not randomly assigned to treatment and control groups through this methodology, findings may be biased if there is inadequate control of the variables. There is a need for new statistical tools to analyze healthcare administrative data. Lawrence McCandless is developing and investigating a new statistical method called a Bayesian propensity score analysis. Through computer simulations, mathematical techniques and models for drug prescribing patterns, the Bayesian analysis will improve the validity of observational investigations of the effectiveness and safety of drugs using large health care administrative databases.
Perfectionism and Social Rejection in the Development of Eating Disorder Symptoms
The causes of eating disorders are complex, yet a number of factors have emerged that may put individuals at increased risk for developing these disorders. These include social factors, such as social exclusion and personality traits, such as perfectionism. With support from a 2003 MSFHR Trainee Award, Brandy McGee studied how perfectionism combines with cultural influences, such as physical ideals suggested in advertisements, to cause eating disorders. Brandy is now exploring how multidimensional perfectionism interacts with experiences of social exclusion to produce eating disturbances. She is testing the hypothesis that social rejection will lead to an upswing in eating disturbances (such as binge eating, thoughts about food, negative mood, etc.) in individuals with high levels of social dimensions of perfectionism, but not in women with low levels of perfectionism. The outcomes of this study will help us better understand how social factors shape health status and enable us to better predict who is at risk for eating problems, and to intervene earlier to promote health.
An adaptive intensity modulated radiation therapy (IMRT) technique through complete on-line treatment plan modification
Radiation therapy uses high energy, penetrating radiation to destroy or stop development of cancer cells, a process which also causes damage to surrounding healthy tissue. Conventional radiation treatment is created using a planning software that generates a plan based on the patient’s internal geometry (position of the target cancer cells and surrounding organs), and this plan remains unchanged for the whole treatment process. The ability to more closely and uniformly target the cancer cells, which includes the ability to map and adjust to changes in the internal geometry between and during treatments, would help to minimize impact to surrounding healthy tissue. A new form of radiation therapy known as adaptive radiation therapy (ART) may hold the answer. This modality allows for modifications of the original treatment plan before each treatment fraction, while the patient is in the treatment room. However, due to time constraints, only a selected set of treatment parameters of the original plan can be modified, which limits the full potential of this technique. Ante Mestrovic is exploring the development of a method for rapid, complete treatment plan modification that characterizes the patient’s internal geometry using three-dimensional ray tracing. His goal is to develop a time-efficient way of adapting treatment plans immediately before each treatment session. This would provide for more precise targeting of cancer cells, helping to reduce radiation exposure to healthy tissue and surrounding organs and contributing to a better outcome for patients undergoing radiation therapy.
Characterizing the role of sumoylation at the budding yeast kinetochore
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.
Cell fate mapping of putative neural stem cells
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.