An important social change of the last quarter century has been a shift in the setting for health care delivery away from institutions — the move from facility-based care to home-based care. In particular, access to palliative home care services has become a major health policy issue in Canada. With an aging population, a growing number of Canadians diagnosed with terminal illness, and almost 90 per cent of Canadians reporting a preference to spend their final days at home, current government policy is pressing for more and better care of the terminally ill in the community. While several conditions are needed to effectively support palliative care at home, two of the most important are the availability of family caregivers (FCGs) and access to services by home care nurses (HCNs). Dr. Kelli Stajduhar is studying the decision-making factors that HCNs take into account when providing specific levels and types of palliative home care nursing services and exploring how the relationships between HCNs and FCGs shape access to care for dying patients. She is interviewing FCGs providing palliative care at home, HCNs and expert clinicians and administrators. Dr. Stajduhar is also observing relationships between HCNs and FCGs to better understand how these interactions affect access to care. Ultimately, results from this research will inform the development of health services, policies and HCNs’ decision making in order to improve access to care for families in palliative care.
Program: Scholar
Structure-based antibiotic discovery on the bacterial membrane
The growing resistance of bacterial infections to standard antibiotic therapies is a major health concern around the globe. The microorganisms that cause serious illnesses such as hospital staphylococcus aureus infections, tuberculosis and meningitis are increasingly developing antibiotic resistant strains both within the hospital and community settings. Some particular bacterial infections, often termed “”superbugs””, have become entirely resistant to all antibiotics currently used in hospitals. Dr. Natalie Strynadka’s research is directed at understanding the way in which bacteria resist current families of antibiotics and at developing new antibiotic drugs that work by inhibiting specific features of the bacterial life-cycle. Her research team will undertake this research by characterizing the three-dimensional atomic structures of molecules critical to the viability of the bacteria, such as their ability to “inject” antibiotic resistant genes into host cells. By describing these structures in fine detail, they will be positioned to design antibiotics that specifically inhibit these critical molecules of the bacteria, destroying its ability to cause disease.
Role of SPARC in cancer therapy
Colorectal cancer (CRC) is the third most common cancer in both men and women, and was responsible for an estimated 8,300 deaths in 2004 in Canada. While there has been an overall decline in the incidence and mortality of CRC in the past two decades because of better cancer prevention, the overall five-year survival rate continues to be poor. This is due in part to chemotherapy resistance, which is common in many solid tumours. Dr. Isabella Tai’s research is directed at understanding the mechanisms enabling cancer cells to become resistant to cancer drugs and other therapies. Using a high-throughput “genomics” approach, her research team has developed a comprehensive list of genes involved in chemo- and radiotherapy resistance. One such gene, SPARC, had low levels of expression in colorectal cancer cells that were resistant to several chemotherapy agents. By increasing the levels of SPARC in therapy refractory cells, response to radiotherapy and chemotherapy was restored and tumor size reduction was observed. Dr. Tai’s team is now examining the general applicability of SPARC-based therapy in other cancer model systems, how it promotes tumor regression, and whether patients who are likely to become resistant to therapy can be identified based on a potential diagnostic marker. The results of the project could lead to improvements in cancer treatment and potentially provide a diagnostic marker to identify individuals likely to develop chemotherapy resistance.
Improving the treatment of posttraumatic stress disorder: A controlled evaluation of a new behavioural treatment
Posttraumatic stress disorder (PTSD) is a common consequence of life-threatening traumatic events (e.g., road traffic collisions, military combat, criminal victimization). PTSD is a severe anxiety disorder that often follows a chronic course and is associated with significant disablement. Existing PTSD treatments are only moderately effective and research is needed to find interventions that can improve treatment outcome. One potential method of improving treatment outcome for PTSD is by reducing anxiety sensitivity, which is described as a person’s fear of experiencing the physical sensations that result from anxiety (e.g. heart palpitations, dizziness) and their belief that these sensations will have harmful consequences. Anxiety sensitivity is elevated in PTSD and is associated with PTSD symptom severity. Interventions that directly target anxiety sensitivity have the potential to enhance PTSD treatment outcome. Dr. Jaye Wald is conducting the first controlled study to examine the effectiveness of interoceptive exposure therapy (IE) on PTSD. While this behavioural intervention has been shown to be effective in treating anxiety disorders, its ability to improve the outcome of existing PTSD treatments has not yet been investigated. Dr. Wald will use IE to repeatedly expose individuals to feared bodily sensations, with the goal of eventually reducing their anxiety sensitivity. Results of this research will have important practical implications for the mental health care field and for individuals with PTSD by enhancing understanding of this disorder and ultimately improving its treatment.
Notch signaling in Lymphoid Neoplasia
A common theme in cancer is the dysregulation of a normal developmental process that either directly causes cells to grow in an uncontrolled manner, or renders them susceptible to cellular damage that, in turn, leads to uncontrolled growth. One example of this process occurs with a normal cellular gene called Notch, which is inappropriately activated in a large fraction of cases of a certain type of blood cancer called T cell acute lymphoblastic leukemia (T-ALL). During normal development of the immune system, regulated Notch activity is required for formation of mature lymphocytes that protect the body from infection. When activated, Notch promotes the formation of normal T lymphocytes, but if this signal is not turned off in time, these T cells can undergo malignant change and become cancerous. Dr. Andrew Weng is studying the signals that are generated by Notch activation and the context in which these signals are received by the cell. By understanding the role of Notch in cancer development, he hopes to develop methods for manipulating Notch activity to shut down the growth of established cancer cells, and perhaps also to prevent it from occurring in the first place.
Tissue microarray analysis of Type 1 growth factor receptor family expression by human breast and colorectal Cancer: prognostic significance and treatment implications
Breast cancer and colorectal cancer are leading causes of cancer-related deaths worldwide. The identification of specific tumor characteristics that would allow for an accurate prediction (prognosticators) of disease course and response to treatment would represent an important advancement in the management of these common malignancies. Unfortunately, no currently known disease prognosticators are reliable in predicting clinical course, or identifying the treatment that would be of greatest benefit to an affected individual. Recently the detection in some tumours of HER1 and HER2 proteins – members of the type 1 growth receptor family (T1GFR) – have shown promise for helping predict patient outcomes and in determining which tumors respond best to specific therapies. These proteins have also recently been used as targets for newly developed drugs to treat these cancers. The expression of the entire T1GFR family (HER1, HER2, HER3, and HER4) by breast and colorectal tumors, and their potential usefulness in predicting disease outcome and patient response to specific treatment(s) has not been explored. Dr. Sam Wiseman is evaluating the expression of the entire T1GFR family in a group of 4500 breast cancer and 500 colorectal cancer samples to determine its relationship to patient treatment and outcomes. His study will be carried out utilizing tissue microarrays, a methodology that allows for the rapid evaluation of large numbers of tumors for molecular markers. The results of this study may lead to improved disease prognostication, outcome prediction, and therapy selection for people diagnosed with breast or colorectal cancer.
Non-surgical cosmetic procedures: health, body image and aging
Non-surgical cosmetic procedures (chemical peels, botox injections, laser hair removal, injectable fillers) are becoming more common than cosmetic procedures (breast augmentation, face lifts, liposuction). Non-surgical procedures are less expensive than cosmetic procedures and thus accessible to more people. To date, research into the perception and experience of non-surgical procedures, which are often viewed as more acceptable, less intrusive and medically risky, have largely been ignored. Dr. Laura Hurd Clarke is examining the perceptions and experiences of women aged 50+, both users and non-users of non-surgical cosmetic procedures as well as the perspectives of physicians who provide the treatments. She is interested specifically in analyzing the relationship between women’s attitudes towards non-surgical cosmetic procedures and their perceptions of health, healthy living, aging and body image. Results from her research will provide insights into the changing norms and social acceptance of the ‘medicalization’ of age-related appearance and a better understanding of the continued blurring of the relationship between health and beauty in contemporary society.
Molecular characterization of Ahi-1, a novel signaling molecule with an SH3 and multiple WD40-repeat domains, in normal and leukemic hematopoiesis
Because many forms of leukemia originate in blood stem cells, uncovering the changes that occur in these cells is crucial to understanding how these diseases develop and progress. Dr. Xiaoyan Jiang is studying Ahi-1, a newly-discovered oncogene (cancer causing gene) that is involved in murine leukemia development (leukemia in mice) and shows abnormal expression in human leukemic cells, including leukemic stem cells from patients with chronic myeloid leukemia and Sezary cancer cells from patients with cutaneous T-cell lymphoma. Her research team recently found that over-expression of Ahi-1 gene alone can cause leukemia in mouse models and suppression of Ahi-1 gene can normalize its transforming activity in human leukemia cells, a strong indicator that Ahi-1 is likely to be an important new oncogene involved in the development of leukemia in humans. Dr. Jiang’s research will explore the normal function(s) of Ahi-1 in the development of blood cells, and how this is altered when cells become leukemic. This research will also begin to identify new intracellular molecules that interact with Ahi-1 and the cellular and molecular pathways through which these interactions occur. Understanding how and by which pathways Ahi-1 contributes to the development of leukemia may provide important new molecular targets for the development of targeted cancer treatment that will be more effective and have fewer side effects than currently used chemotherapy.
Creation and function of neighborhoods in eukaryotic chromosomes: regulation by SWR1-Com, a desposition complex for histone variant H2A.Z
Chromatin is the complex of DNA and protein material that make up chromosomes, home to the genetic code. The basic unit of chromatin is the nucleosome, a fundamental building block consisting of DNA wrapped around an octamer of histone proteins. A large number of proteins involved in cancer development and the genetic susceptibility to devastating diseases such as Ataxia Telangiectasia (a progressive immunological and neurological disorder) act through modification of chromatin structures and interfere with normal chromatin function. Differences in chromatin structures between adjacent regions specify the properties of larger macrodomains called neighbourhoods. The shape and structure of these neighbourhoods influence chromosome behavior, while complex regulatory mechanisms that ultimately involve chromatin ensure that each cell expresses only the appropriate genes, duplicates its genome with high fidelity, divides only when required, all while combating constant assaults on its DNA. Failure in any of the mechanisms regulating these events can lead to disease. These chromatin structures themselves can also be inherited, creating an additional complex set of influences that are crucial for the identity and activity of the cell. The molecular biology of chromatin structures and their role in chromosome biology and genome function in health and disease is the focus of Michael Kobor’s research. Specifically, he is studying a unique chromosomal neighbourhood containing a specialized histone variant known as H2A.Z, which is deposited into chromatin by a large protein complex. Using innovative genome-wide approaches, Dr. Kobor’s team aims to uncover the rules and principles of histone variant function.
Pharmacist identification of new, diagnostically confirmed osteoarthritis (PHIND-OA)
Knee osteoarthritis is the most common cause of disability in older adults. There are three million Canadians currently afflicted with this condition, and it’s predicted that this number will increase by 50 per cent by 2020. The costs of medical care, drugs, and lost wages resulting from this disability is a major economic burden in Canada. Several research studies have demonstrated the benefit of non-drug therapy such as education and exercise for people with knee osteoarthritis. However, many individuals remain undiagnosed for their condition and don’t receive appropriate interventions. Dr. Carlo Marra is researching the potential of pharmacists, who are highly accessible health care practitioners, to help identify people with knee osteoarthritis by using a simple screening questionnaire. Next, he will investigate whether pharmacists can initiate an intervention that brings together patient, physiotherapist, and family practitioner to improve physical function, minimize pain, and reduce the economic burden of this disease. In addition, regular follow-ups will occur to assess and encourage compliance with the intervention, assess outcomes and answer any questions. Dr. Marra anticipates his research will demonstrate the value of this innovative, cost-effective strategy to improve outcomes and quality of life for people with knee osteoarthritis.