$10.4 million investment in transformative health research
The Canadian Institutes of Health Research has awarded $10.4 million in funding to support University of Manitoba researchers investigating health issues affecting the lives of Canadians.
“These researchers are doing cutting-edge studies that will benefit individuals coping with disabilities, distress, and many serious life-threatening conditions,” says Dr. Digvir Jayas, vice-president (research and international) and Distinguished Professor, University of Manitoba. “Their work is testament to the outstanding calibre of transformational research conducted at the University of Manitoba and at our affiliated partner organizations.”
The researchers and their projects are:
Pharmacology and Therapeutics, Max Rady College of Medicine; Investigator, St. Boniface Albrechtsen Research Centre, Children’s Hospital Research Institute of Manitoba
Project: Sex-based differences associated with mitochondrial dysfunction in Alzheimer’s disease
Women have a higher risk of acquiring Alzheimer’s disease (AD) and it’s not known why. Differences in cellular mechanisms (genetics, metabolism), hormonal changes, and/or lifestyle factors between men and women may be at the root cause, but no one knows for sure. This study aims to bring a clearer picture into view of the biological processes underway in the onset of Alzheimer’s disease.
Physiology and Pathophysiology, Max Rady College of Medicine; Investigator, St. Boniface Albrechtsen Research Centre
Project: Targeting scleraxis to combat cardiac fibrosis
Heart disease is the primary cause of death in the western world. Cardiac fibrosis is a stiffening of the heart caused by many forms of heart disease. Fibrosis dramatically increases the risk of death and disability independently of other risk factors (up to 17 times), yet no treatments for cardiac fibrosis are available to patients. Czubryt’s laboratory has identified a protein (scleraxis) as a powerful cause of fibrosis, and initial data indicates that interfering with scleraxis can reduce fibrosis. This study will further probe this relationship in the hop of finding new treatments for fibrosis.
Physiology and Pathophysiology, Max Rady College of Medicine; Investigator, St. Boniface Albrechtsen Research Centre
Project: Ski is a negative regulator of cardiac fibrosis
Patients surviving a heart attack or those with hypertension develop chronic heart disease. These patients make too much collagen in their heart muscle, wherein non-muscle cells called myofibroblasts secrete excessive collagens, which stiffens the heart. Most of the “glue” (extracellular matrix) between muscle cells in healthy hearts is made of tough collagen proteins. Too much collagen leads to cardiac fibrosis, which results in weak muscle contraction and relaxation. Despite this, there is currently no treatment for cardiac fibrosis, nor are there any specific cardiac drugs approved to fix cardiac fibrosis. In recent years, we have found a new protein called Ski. Ski turns off this over-deposition of matrix, in diseased heart cells. Further, we have made progress of how Ski actually achieves this positive change. We are now poised to extend our understanding of how Ski corrects cardiac fibrosis and this study aims to bring about the design new Ski-based therapies to treat cardiac fibrosis, for the prevention of heart failure.
Pharmacology and Therapeutics, Max Rady College of Medicine; Investigator, St. Boniface Albrechtsen Research Centre
Project: Muscarinic receptor antagonism as a novel mechanism for sensory nerve repair
Objective Diabetic sensory neuropathy and chemotherapy-induced peripheral neuropathy (CIPN) are neurodegenerative diseases characterized by loss of nerve fibers in the skin. Both diseases cause significant pain and eventually lead to sensory loss. The impact of these diseases on human health is enormously damaging and there are no therapies. Recent work in Fernyhough’s lab has uncovered an endogenous signaling pathway in neurons that negatively modulates nerve fiber growth of sensory neurons. This study will enable the lab to broaden in scope and permit this therapeutic approach to be performed in a wide range of distal dying back neurodegenerative diseases.
College of Rehabilitation Sciences
Project: Evaluation of a peer-led eHealth wheelchair skills training program: Training to Enhance Adaptation and Management for Wheelchair users (TEAM Wheel)
Mobility impairment is the third most common disability; nearly 300,000 Canadians use a wheelchair or scooter because their disability makes walking difficult. Many Canadians receive their wheelchair while in hospital and must learn to contend with the social and environmental challenges of use when they return home. Because of shorter hospital stays and reduced access to outpatient rehabilitation services, wheelchair users often receive little training in how to operate and manage their mobility device. Without the appropriate skills, wheelchair users can experience health declines, diminished physical activity, and restricted participation in activities of life. The impact of reduced independence can have social and financial costs for the individual, their caregivers, and the health care system. Training to Enhance Adaptation and Management for Wheelchair users (TEAM Wheel) is a novel intervention designed to address this important transition to wheelchair use.
Pharmacology and Therapeutics, Max Rady College of Medicine; Investigator, Kleysen Institute for Advanced Medicine, Health Sciences Centre and Children’s Hospital Research Institute of Manitoba
Project: Microglia and cognitive impairments in offspring exposed to gestational diabetes mellitus
Maternal diabetes is the most common complication in pregnancy affecting up to 18 per cent of pregnancies. Maternal diabetes increases offspring risk for developing various health problems. Population studies have demonstrated that maternal diabetes increases offspring risk to have learning and memory deficits, and behavioral issues. Maternal diabetes is associated with elevated inflammation status, which can be detrimental for the developing brain. This study will identify the role of brain immune cells and the mechanism by how they can impair brain cells function. It will also assess whether maternal gestational diabetes differentially affects male and female offspring. The ultimate goal is to identify targets for drug development and promote healthy brain development and, thus prevent cognitive impairments in children of mothers with gestational diabetes.
Community Health Sciences, Manitoba Centre for Health Policy, Max Rady College of Medicine
Project: Understanding cancer burden and outcomes for Canadians living with intellectual and developmental disabilities
Not all Canadians have the same cancer risk, receive the same quality of healthcare after a cancer diagnosis, or have the same prognosis. This may be the result of many things including how much money someone has, their education, where they live, or discrimination within the healthcare system that causes people to be treated differently, regardless of how sick they are. Although cancer is a leading cause of death for Canadians living with intellectual disabilities and developmental disabilities (IDD), they may be less likely to receive high quality cancer treatment compared to other Canadians. Because people living with IDD are more likely to live in vulnerable circumstances (such as those described above), this may impact how quickly their cancer is diagnosed, their access to life-saving treatment and result in worse outcomes. The goal of this project is to determine whether or not Canadians living with IDD are more likely than Canadians who do not have IDD to be 1) diagnosed with cancer; 2) diagnosed with incurable cancer; 3) not receive the right cancer treatment; and 4) to die of their cancer. This study will highlight ways to improve the quality of care provided. We will work with our policy partners to ensure this information is usable and informative to the care of underserved cancer populations.
Microbiology, Faculty of Science
Project: Development of a therapeutic modality to treat GM2 gangliosidoses
Tay-Sachs disease and Sandhoff Disease (also knows as the GM2 gangliosidoses) are inherited neurodegenerative diseases that result from genetic mutations that inactivate an enzyme known as HexA. HexA is a protein in our cells that degrades GM2-ganglioside (GM2), a molecule found primarily on neurons of the central and peripheral nervous system. HexA degrades GM2, and if it is not active, GM2 rapidly accumulates and causes severe neurological disease.The rate of GM2 accumulation depends on how severely the genetic mutations impact HexA activity. Mark’s lab has recently engineered HexA to markedly improve its stability and function for enzyme replacement therapy. This study will use the engineered enzyme, known as HexM, to develop an enzyme replacement therapy that will be evaluated in models of GM2 gangliosidosis in combination with a drug known to rescue residual HexA activity in cells. The approach holds promise to reduce GM2 accumulation and reverse the progression of this debilitating family of neurological diseases.
Immunology, Max Rady College of Medicine
Project: Control of B cell metabolism by the PI3K pathway: applications for autoimmunity
The immune system is critical to human health. In order to develop vaccines and treatments for diseases where the immune system malfunctions (such as autoimmunity, inflammatory diseases or immunodeficiency), we need to better understand the fundamental mechanisms governing immune responses. Our research deals with the arm of the immune system responsible for producing antibodies, which are specialized proteins that bind to microorganisms and target them for destruction by the immune system. Antibodies are secreted into the blood and mucosal surfaces by cells called B lymphocytes. This study aims to define the molecular signaling pathways that regulate the activities of B lymphocytes during normal immune responses or abnormal autoimmune responses. The work is identifying new molecular pathways that can be targeted to shut down B cells and treat autoimmune disease.
Biochemistry and Medical Genetics, Max Rady College of Medicine; Investigator, Research Institute of Oncology and Hematology, a joint institute of the University of Manitoba and CancerCare Manitoba
Project: Exploring and Exploiting Reduced USP22 Expression in Colorectal Cancer
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in Canada, and although advances in treatment options have improved the overall survival for early stage CRCs, about 50 per cent of individuals are still diagnosed with late stage disease that is often incurable. The development of highly specific, anti-cancer treatments is a significant research challenge; however, recent efforts suggest that exploiting the mutated genes and abnormal pathways that drive cancer development may hold tremendous clinical potential. Accordingly, greater insight into the mutated genes and abnormal pathways driving CRC formation is needed so that new treatment strategies and drug options can be developed that exploit them. McManus’s lab will build on its past discoveries to identify novel drug targets and lead chemotherapeutics that will be tested in pre-clinical studies to ideally and ultimately deliver new therapeutic options to individuals diagnosed with CRC.
Community Health Sciences, Manitoba Centre for Health Policy, Max Rady College of Medicine; Investigator, Children’s Hospital Research Institute of Manitoba
Project: Health, Well-Being, and Disease-Birth to Adulthood in Manitoba
Why are some children healthy and others not? Why do some children perform well in school and others drop out? Why are some youths arrested while others never come near the justice system? The population-based Manitoba data enable research on the consequences of birth, childhood, and adolescent experiences for health and well-being over the first 20 years. This study will explore the degree to which predictors of poor young adult outcomes occur early enough to allow the possibility of intervention. Roos’s lab will analyze Manitoba’s data on several government projects designed to improve children’s wellbeing.
Chemistry, Faculty of Science; Medical Microbiology, Max Rady College of Medicine
Project: Preclinical studies on aminoglycoside-derived antibiotic adjuvants (AGDAAs)
According to the United Nations (UN) and the World Health Organization (WHO) antimicrobial resistance (AMR) is one the largest threats to public health and economic growth. Recently, the WHO for the first time divided pathogens into three categories according to the urgency of need for new antibiotics: critical, high and medium priority. The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. To overcome the bottleneck in antibacterial drug discovery, this study aims to develop helper molecules (adjuvants) designed to enhance membrane permeability, reduce efflux of antibiotics and prevent or delay resistance development against these pathogens. The overall goal of this proposal is to identify optimized helper molecules capable of rescuing antibiotics from resistance in animal models of infection against multidrug-resistant priority pathogens and to understand their mode of actions.
Kellie Thiessen and Katherine Whitecloud (Assembly of First Nations)
College of Nursing and Children’s Hospital Research Institute of Manitoba; and
Project: Welcoming the ‘Sacred Spirit’ (child): Connecting Indigenous and Western ‘ways of knowing’ to inform future policy partnerships to optimize maternal child health service delivery initiatives in remote Canadian regions
Ongoing and historical colonial health practices have systematically diminished the health and well-being of Indigenous communities. One critically important primary healthcare service that shows the impact of colonial relations is maternal/child healthcare. There is the “absence of teachings regarding the ‘Sacred Spirit’ (child) along with the responsibilities and preparation for ‘life-giving’ across the childbearing continuum (preconception, pregnancy, birth and post-delivery). Strategies to embrace and include Indigenous knowledge, values, teachings, and stories are essential for a healthy life in Indigenous communities; the absence of these strategies disrupts the relations among youth, young parents, families, and communities. In this study, we explore maternal healthcare delivery systems and services across 4 remote Canadian jurisdictions. Our exploration includes Indigenous and Western world views and aims to improve the health of communities by bringing back the ‘Sacred Spirit’ [child]. The teaching tells us that achieving this equates to maintaining wellness. We have and will continue to actively engage Indigenous and non-Indigenous members in 4 remote Canadian jurisdictions each involved in delivering or receiving maternal care. Data sources include interviews, focus groups [story-telling], and document analysis. The outcome will be identification of maternity care delivery models that are integrated, cost-efficient, culturally appropriate, and effectively supporting persons to maintain health and wellness within their own community.
Canada Research Chair in Child and Family Engagement in Health Research and Healthcare, College of Nursing; Investigator, Children’s Hospital Research Institute of Manitoba and St. Boniface Albrechtsen Research Centre
Project 1: Designing a Responsive and Integrative Model of Respite Care for Families of Children with Complex Care Needs and Conditions (CCNC) through Patient-Oriented Research
Children with complex care needs and conditions (CCNC) are those with chronic physical and developmental disabilities who require multiple services. Caring for children with CCNC is an immense undertaking for families that involves constantly coordinating multiple needs and services in a complex system with limited supports. As such, family well-being can be greatly impacted. The goal of this study is to provide evidence to inform the design of a new model of respite care that can respond to the diverse and changing needs of families of children with CCNC in Manitoba (MB).
Project 2: Non-suicidal self-injury among youth: Perspectives of youth who self-harm, their families and service providers
Self-harm among youth is a major public health concern. Usually first occurring in early adolescence, it is estimated that 18 per cent of youth engage in self-harming behaviours at some point in their lives. These may include cutting, self-hitting, pinching, scratching, burning, minor overdosing and interfering with wound healing. Recent media reports reinforce that self-harming provokes a great deal of suffering among youth and their families, who struggle to access appropriate care. Likewise, service providers find it difficult to treat youth who self-harm. While self-harming can have a significant impact on a youth’s life, it is poorly understood. Before we can develop effective services and supports, we first need to gain an understanding of self-harm from the perspectives of youth who self-harm and their families as well as service providers who support them. The aim of this study is to increase our understanding of the experiences and needs of youth who self-harm and their families. This information is essential in order to design better services and supports for this population.