2024 MMSF Research Grant Recipients
The Manitoba Glomerular Diseases Registry and Biobank
Dr. Bryce Barr
Glomerulonephritis (GN) is a group of kidney diseases caused by the immune system that affect individuals at a younger age compared to other kidney diseases. GN affects millions of people worldwide, and in Canada, it’s the second leading cause of kidney failure.
For people with GN, treatment aimed at preventing kidney failure involves the use of medicines that lower the immune system. These medicines have serious side effects, including the development of severe infections and cancers. Currently, doctors do not have a good understanding of which patients can benefit from more or less treatment, potentially leading to harmful over-treatment in some individuals and under-treatment in others.
By examining data from large groups of patients, we can better understand the factors that can cause some people to be more likely to reach kidney failure, as well as gain a better understanding of medication side effects and who can best benefit from treatment.
The goal of this project is to create and maintain a registry containing information from all patients with GN in Manitoba, which will improve our understanding of who gets GN and, their characteristics, including who progresses to kidney failure. Further, we will collect a blood and urine sample from each new patient undergoing a kidney biopsy. This will help identify new blood and urine tests which can tell doctors whether the patient needs more or less treatment.
This project will improve our ability to identify patients earlier in their disease and individualize treatment, reducing kidney failure risk while also reducing side effects, thus improving the care and quality of life for patients with GN.
Incidence and impact of persistent opioid use after cardiac surgery in Manitoba
Dr. Andrew Fagan
Opioids play an important role in surgical pain management, but recent information has shown that overuse can lead to longer term abuse known as persistent opioid use (POU). There is growing concern that the overuse of opioids after surgery is contributing to the opioid crisis.
Estimates have found that one in 10 patients have long-term problems with ongoing dependency on opioid medications, particularly people who have rarely used these medications before surgery. The incidence and long-term impacts of POU after cardiac surgery in Manitoba is unknown.
Manitoba has a unique and world- class database at the Manitoba Centre for Health Policy (MCHP). We seek to study POU in what will be one of the largest studies in Canada. We will look back from 1995 to 2016 to see how common POU has been and its effects on patients and the healthcare system. We will take a deep look at the health, environmental, and social factors that affect these patients.
This study will provide important information on how routine hospital pain management after heart surgery has affected patients in the past and how providers can develop new methods – including non-opioid methods to enhance a patient’s recovery. The results will be used to develop safer prescribing practices in hospitals and inform healthcare policy in Manitoba and the broader global surgical community.
Evaluating ultrasound-guided nerve injection for chronic knee pain: a cadaveric study
Dr. Terry Li
Chronic knee pain affects many people globally. Current treatments can be ineffective and/or very expensive. Ultrasound-guided nerve injection shows promise in alleviating this pain by delivering chemicals that kill nerves transmitting pain signals from the knee. However, ultrasound landmarks for these nerves and the spread of injected chemicals in tissue are not well understood.
To address this, we plan to find nerves of the knee joint in human cadavers using ultrasound-guided injection and dissection. We will preserve the cadavers using a method that maintains life-like tissue properties and allows the body to be imaged by ultrasound. We will inject a nerve-killing chemical mixed with a stain at five points around the knee, targeting nine different nerves. Then, the skin and muscles will be carefully cut open to reveal the areas stained by injections and nerves of the knee joint.
We aim to describe differences in the distribution of these nerves between people. We will evaluate the spread of the injected chemical in terms of its coverage over nerves and its leakage to surrounding structures. We’ll identify accurate injections that cover target nerves, and we’ll determine which factors lead to inaccurate injections and potential leakage to neighboring structures.
The study's anticipated results will show how to use ultrasound on the nerves that transmit pain signals from the knee. We hope to demonstrate that ultrasound-guided nerve injections around the knee are effective and safe. This knowledge will encourage more physicians to use this treatment to relieve chronic knee pain for patients.
Surgical outcomes and complications following outpatient surgery at a new Men's Health surgical facility and development of a prospective registry to evaluate post-procedure complications
Dr. Premal Patel
The COVID-19 pandemic has caused significant increases to the surgical backlog, with patients waiting months and even years for surgery. Men’s Health Clinic Manitoba has been created to be an outflow to the healthcare system. By diverting certain urologic surgical procedures out of hospital, the clinic helps unburden the healthcare system and make efficient use of the current main hospital resources for more invasive procedures.
We believe outpatient procedures are safe and effective for a number of urologic issues, with limited complications and visits to the healthcare system after a procedure (less than five per cent), with high rates of patient satisfaction.
We have been performing urologic procedures at the clinic since August 2022. In this study, we aim to determine the rate of post-procedure complications, healthcare visits and patient-related tolerability, as well as create a prospective registry that tracks all post-procedure complications and healthcare visits of all procedures performed at the clinic.
We anticipate that we will demonstrate a low rate of surgical complications and healthcare visits after procedures performed at the clinic (less than five per cent) with high patient tolerability (over 90 per cent). Additionally, by creating a prospective registry for complications and healthcare visits, this will allow us to ensure the safety of procedures performed at our facility in real-time and provide meaningful contributions to the literature.
Targeting gasdermin D-mediated cell death as a potential therapeutic approach against RSV infection
Dr. Barbara Porto
Last winter, Manitoba experienced a bad season of respiratory syncytial virus (RSV), with many cases in children. RSV is a major cause of respiratory illness in young children. The virus usually causes a common cold, but children under a year old are most at risk of developing a serious and even life-threatening infection in the small airways of the lungs.
There is no vaccine or effective antiviral treatment for children. Manitoba does have an RSV prophylaxis program that provides a treatment (palivizumab) against RSV infection. However, since the treatment is very expensive, it’s only given to those young children at the highest risk for a severe disease.
Therefore, we need a better way to treat and stop the spread of RSV in young children. A method known as drug repurposing identifies existing drugs that can be used to treat diseases other than those for which they were intended. This saves money and time in developing new treatments.
Here, we will study the repurposing of disulfiram, a drug used to treat alcoholism, against RSV infection. Our preliminary results show that disulfiram reduced RSV infection of lung cells. We will study the antiviral effects of disulfiram against RSV infection using cells collected from healthy volunteers , and a mouse model of RSV infection.
We will test the efficacy of different treatment times with disulfiram and whether it decreases inflammation and viral spread. Drug repurposing using disulfiram could lead to a novel strategy to treat RSV infection in young children.
Exploring the association between autism spectrum disorder and immigration in Manitoba, a population-based approach
Dr. M. Florencia Ricci
Given the significant and rapid increase in the number of children diagnosed with autism spectrum disorder (ASD), studies are needed to understand what factors could be contributing to this rise. A possible association between ASD and immigration has been studied in many countries, but not in Canada.
Concerned about a potential link between immigration and ASD in Manitoba, we recently completed a study that showed an over representation of immigrant families among children who were diagnosed with ASD at the primary site for evaluation of ASD in Manitoba. Since the information used for this study was taken retrospectively, we found limited information on immigration characteristics, family composition factors and educational outcomes.
We are now aiming to link our ASD data to the Manitoba Population Data Repository, which contains health, education, and sociodemographic (including immigration) data from all Manitoba residents. Using the Manitoba Population Data Repository, we will determine provincial-level differences in the number of ASD diagnosis between Manitoba children who belong to immigrants versus non-immigrants families. We will also compare demographic characteristics and the presence of associated medical diagnosis as well as kindergarten-readiness between them.
This will be the first study that looks at a possible link between immigration and ASD at a provincial level in Canada. We hope this work leads to a better understanding of how and what aspects of parental immigration may increase vulnerability to ASD so that interventions can be targeted to at-risk communities in our province.
Discovering genes involved in the co-development of psychiatric comorbidities in inflammatory bowel disease
Dr. Razvan Romanescu
Inflammatory bowel disease (IBD) affects 11,000 Manitobans. An estimated 40 per cent of people affected also have mental health disorders, including anxiety and depression, a rate that is significantly higher than in the general population.
The reason why both IBD and mental health disorders tend to appear together is unknown but thought to be related to genetics. Although there has been some success in understanding the genetic factors underlying each condition separately, understanding their co-appearance requires more powerful detection tools.
We propose a new statistical method that detects when a pair of genetic factors interact. It will also determine, how much having both factors increases the risk of an IBD patient developing mental health complications.
To discover these associations, we will use data from the UK Biobank, a large study from the United Kingdom of over 500,000 people. We will compare the genetics from participants affected by both IBD and mental health disorders with IBD patients without mental health complications, as well as with healthy controls.
To ensure the validity of our results, we will cross-check our findings in a similar cohort of patients from Manitoba. By identifying the genetic factors underlying complications in IBD, we can use these genetic factors to determine which IBD patients are at high risk of developing mental health disorders, leading to preventative measures or earlier treatment.
Establishing 3D gut model analyses to uncover novel immune pathways to target in inflammatory bowel disease
Dr. Deanna Santer
Inflammatory bowel diseases (IBD) are serious and lifelong, affecting one in 150 Canadians. Current drugs used for IBD do not work in all patients, and they mostly block the immune system. This increases the risk of infection and can cause side effects.
Immune proteins called interferon(IFN)-lambdas are different. IFN-lambdas help gut health in IBD mouse studies, but studies about human IFN-lambdas in the gut are lacking.
We found that the IFN-lambda system does not work properly in people with IBD. This means a key part of the immune system needed for gut health may be missing in IBD patients. A safe IFN-lambda drug already exists for viral infections and could be used in IBD if we find out how it could be helpful.
To study IFN-lambda biology, we need to set up human gut biopsy methods. We can take biopsies during a regular colonoscopy and expose them to IFN-lambdas in the lab, instead of needing to test in animals or people first.
We will find out what kinds of gut cells respond to IFN-lambdas, and how these interactions affect gut health. Our long-term goal is to find out if IFN-lambda pathways can be promoted as a new and safe therapy for IBD to help heal the gut and decrease symptoms to promote remission without suppressing the immune system.
Artificial intelligence in modernizing emergency department: from strategic planning to optimizing operational performance
Dr. Farzad Zaerpour
Our emergency departments (EDs) are facing severe overcrowding issues and delays in timely care. To tackle this problem, we propose using artificial intelligence (AI) and machine learning to develop a data-driven patient flow model to help healthcare providers optimize resources, reduce wait times, and improve patient outcomes. This project makes a significant impact on several critical aspects of healthcare delivery, including:
- Reduced ED crowding and improved patient outcomes: The proposed model can potentially enhance the quality of care and overall patient outcomes by optimizing patient flow. For example, if our EDs can provide timely and appropriate care, patients will be less likely to face complications or require follow-up visits.
- More efficient use of resources: By identifying bottlenecks in the patient-flow process and optimizing resource allocation, the model can help healthcare providers make more efficient use of their resources, reducing costs and improving efficiency.
- Structured decision-making: The AI-based tool can help decision-makers make more informed and effective patient-care and resource-allocation decisions by using real-time data and predictive analytics.
- Better capacity planning: By predicting peak hours and allocating resources accordingly, the model can help healthcare providers plan for capacity needs more effectively, improving overall efficiency and reducing wait times.
We believe that the impact of this project is significant, and it has the potential to improve the quality of care, reduce costs and enhance the overall efficiency of healthcare delivery.
Dr. Brenton Button
Exploring the impacts of extreme weather on children during the school day
Outdoor school recess is an important part of the school day. It gives children chances to be active, spend time outside and play with friends. These activities have been linked to improved health and well-being.
Due to school rules, approximately 30 per cent of recesses are modified to be indoors under certain weather conditions. During indoor recess, children have fewer chances to be active, play outside or play with friends.
This project aims to work with children to explore their thoughts and feelings of play in extreme weather and during indoor recess. Manitoba has some of the harshest winters in Canada. These findings can help change rules to give students chances to play and be active during indoor recess.
Dr. Catherine Card
Convergence of epidemics: The effects of methamphetamine use and concurrent STBBI on the immune system and HIV susceptibility
There is a merging between the methamphetamine (meth) and HIV epidemics. Since 2018, more than half of new HIV infections in Manitoba have been among people who inject drugs (PWID), with meth as the leading substance injected.
People who inject drugs are more likely to have multiple infections transmitted by sexual contact or blood products (referred to as STBBI), and women tend to be more affected than men. Meth use and STBBI can have dramatic impacts on the immune system, with each independently leading to inflammation and increased susceptibility to other infections, including HIV. However, the combined effects of meth use and STBBIs on inflammation and immune system function in PWID are unclear.
This study aims to address these gaps in knowledge by measuring inflammation, immune cell activation and immune function in blood samples from PWID who use meth. We’ll also try to determine whether STBBIs further aggravate these immune outcomes.
We’ll also test the extent to which cells from the study participants are readily infected with HIV in the lab, to see whether the immune outcomes are related to HIV susceptibility. We will explore how biological sex and gender impact these effects in PWID.
This study will reveal important information regarding the immune health of PWID. It’ll help guide approaches to engaging them in STBBI prevention and harm reduction strategies that address their needs.
Dr. Sabrina Lee
Travelling for Abortion Care: A Critical Qualitative Analysis of Experiences Accessing Therapeutic Abortion in Winnipeg
Despite Canada’s global leadership in reproductive rights, there remain significant barriers to accessing comprehensive abortion care due to inequitably distributed services, prohibitive costs due to loss of employment and travel, and lack of knowledge among providers and those seeking abortion services.
With the vast majority of abortion care involving a surgical procedure, comprehensive abortion services are concentrated in large cities along the southern border of Canada. The recent introduction of mifepristone (the gold standard in medication abortion) following Health Canada approval in 2015 and commercial availability in 2017 has transformed the Canadian abortion care landscape. This oral regimen offers the opportunity to improve the geographical inequities described in the literature when examining access to abortion services.
This qualitative study aims to provide insight into the experiences of those travelling to Winnipeg for both surgical and medical abortion care. We hypothesize that experiences of people travelling to Winnipeg for abortion care will similarly reflect logistical, emotional, and financial barriers associated with travelling for abortion care. Using Critical and Feminist lenses, we will conduct semi-structured interviews to achieve the following objectives:
- To explore the experiences of those travelling at least one hour by road or any travel-time by flight to Winnipeg for induced abortion services.
- To understand the process behind the choice of abortion method in those travelling at least one hour by road or by flight to Winnipeg for induced abortion services.
- To investigate perceptions and attitudes towards surgical and medical abortion among those travelling at least one hour by road or by flight to Winnipeg for induced abortion services.
- To provide insights into facilitators and barriers to accessing abortion services in those travelling at least one hour by road or any time by flight to Winnipeg for induced abortion, potentially identifying areas for improvement in abortion health policy and abortion service delivery.
This study will add unique insight to the young knowledge base in Canada of experiences in those needing to travel for their abortion care. Our results will have the potential to improve abortion services in rural and remote areas, improve our understanding of travel experiences for abortion care when necessary, and bolster provider knowledge in ways to better serve this particular population in the outlined circumstances.
Dr. Devin Lemmex
The impact of varying weightbearing restrictions on postoperative outcomes following arthroscopic surgery for femoroacetabular impingement: a randomized trial
Femoroacetabular impingement is a condition of the hip that primarily causes pain in young and active individuals. It is caused by irregularities in the shape of the bones that make up the hip joint, leading to tears in the cartilage. It can eventually lead to arthritis.
To treat this condition, patients often undergo lengthy periods of physiotherapy, use anti-inflammatory medication and undergo injections into the joint. However, if these are not effective, then surgery may be performed.
This type of surgery is done through small incisions, using a camera, and is minimally invasive. The available studies evaluating this type of surgery tell us that it is safe, reproducible and very effective.
Despite technological advances and modern techniques used inside the operating room, it is unclear on how patients should start their rehabilitation process afterwards. Specifically, should they be using crutches to protect the hip from weightbearing, or should they begin walking as soon as possible? This is a simple question but one that potentially can make a big difference in early recovery and comfort after surgery.
This study aims to help answer that question by comparing patients placed into two separate groups and following their post-operative outcomes. We will also be evaluating our physiotherapy techniques to determine when a patient is fit to return to sports after this type of hip surgery.
Dr. Paul Marcogliese
Discerning neuroregressive ataxia and autism in two novel knock-in mouse models.
Manitoba has a critical, unmet need to understand and treat developmental disorders, including autism spectrum disorder. We and others have identified different types of variants in the gene called IRF2BPL associated with both autism spectrum disorder and a highly severe neurological disorder that presents in children around the age of five years old called NEDAMSS.
Although variable, NEDAMSS patients have neurological regression including loss of speech, loss of developmental milestones, seizures, and movement abnormalities where they eventually become immobile in adolescence. Beyond being an important human disease gene, IRF2BPL is an interesting gene as it is enriched in the brain and mostly unstudied.
We and our collaborators have made models of IRF2BPL in fruit flies and zebrafish. However, there are no models in mice, which are needed for translating pre-clinical drug screening studies to patients. In this proposal, we have generated two patient-specific mouse lines associated with either autism or NEDAMSS. We will characterize both of these novel mouse models, determining if there are behavioural defects as well as pathology in the brain.
Moreover, we can use these two mouse lines to discern, mechanistically, why certain mutations lead to autism spectrum disorder and other mutations lead to a severe neurological disorder like NEDAMSS. Both models will deepen our understanding of neurodevelopment and neurodegeneration.
Neurodevelopmental disorders in Manitoba
Manitoba has some of the highest rates of neurodevelopmental disorders in Canada, having specific populations where novel gene variants have been identified. Moreover, autism spectrum disorder has seen an increased prevalence in Manitoba. Importantly, few if any of these neurodevelopmental disorders or autism spectrum disorders have approved therapies that can reverse or prevent them. Hence, there is a clear need for basic studies to both inform on pathogenic mechanisms and to develop pre-clinical models for therapeutic testing.
Dr. Leslie Redmond
Development of a Culturally Appropriate Gestational Diabetes Mellitus Prevention Program for Urban-dwelling Indigenous Individuals in Manitoba
This project will develop an intervention that will aim to decrease the risk of gestational diabetes mellitus, or GDM, in urban-dwelling Indigenous people in Manitoba.
GDM is a serious health condition that can put both the pregnant person and the baby at risk for complications, both during pregnancy and well into the future. Preventing GDM is especially important for Indigenous people, as prevalence is high and many other health disparities are also present.
Country foods (foods supplied by the land) and lifestyle activities have many health benefits, including the prevention of type 2 diabetes and GDM. However, country foods and lifestyle activities are less available and accessible to urban-dwelling Indigenous people in Canada, and those at risk for GDM may not be able to benefit from them.
This project will work with urban-dwelling Indigenous people and stakeholders committed to improving Indigenous health to develop a GDM risk-reduction intervention that focuses on country foods and lifestyle activities. We hope that this intervention will lead to improved personal health of urban-dwelling, pregnant Indigenous people and contribute to overall better population health through the prevention of health risks and complications in future generations.
Dr. Inna Rabinovich-Nikitin
Circadian Dependent Cardiometabolic Heart Failure
Shortness of breath (dyspnoea) is a common, debilitating symptom that affects patients with respiratory disease, but it also occurs in healthy adults during physical exertion. Females report greater levels of dyspnoea during exercise and activities of daily living than males, but it is unclear why. Most research has focused on how biological factors (such as lung size, airway size, and pulmonary function) influence the perception of dyspnoea in males and females; however, these biological factors fail to fully explain sex differences in dyspnoea. Gender, which encompasses several psychological, social and cultural factors, may better explain why females experience dyspnoea more than their male counterparts.
This study seeks to determine the impact of both sex and gender on the perception of dyspnoea in healthy males and females. To accomplish this goal, male and female participants will undergo detailed analysis of gender-related factors, pulmonary function testing, exercise testing, and a series of experimental trials designed to provoke sensations of dyspnoea. Throughout testing, the perception of dyspnoea will be evaluated using validated scales, while the ventilatory, cardiovascular and metabolic responses will be recorded using a cardiopulmonary testing system. We will determine, for the first time, how gender-related factors influence the perception of dyspnoea.
The results of this study will contribute to improving our understanding of causes of dyspnoea and how they may differ in men, women, boys, girls, and gender-diverse individuals. This work is important given that dyspnoea is an independent predictor of mortality, is remarkably common in older adults, and is difficult to treat effectively.
Dr. Ayesha Saleem
Uptake of fetal extracellular vesicles (EVs) across placental barrier
The process of cell-to-cell communication involves small bubbles of cellular material called extracellular vesicles (EVs), which are released from all cells.
Think of EVs as emails – just like an email can have text, video or audio files, EVs are versatile in the messages they can carry. EVs can hold different combinations of proteins, fatty acids and nucleic acids, and this cargo can change depending on the cell type of origin, physiological conditions, and the intended recipient cell.
Several studies have explored the mechanisms of EV synthesis and release and catalogued the variety of enclosed biochemical content.
Interestingly, EVs have been shown to cross physiological barriers, like the blood-brain barrier. If EVs can cross the (almost impenetrable) blood-brain barrier, it is likely that they can also cross the placental barrier. This makes them ideal candidates for mediating communication between fetus and mother.
This project will investigate whether EVs form the main biological communication link between mother and fetus. If fetal EVs can be detected in maternal blood/tissues, it will not only advance basic science knowledge, but also lead to the development of improved blood-based diagnostic markers that can be used to identify fetal abnormalities in a timely and safe manner. Early diagnosis may help prognosis and facilitate improved health outcomes for the unborn child.
Dr. Diana Sanchez-Ramierz
Effect of Pulmonary Telerehabilitation and Telemonitoring for patients with chronic respiratory diseases: a feasibility study.
Pulmonary rehabilitation (PR) has shown great benefits in patients with chronic respiratory diseases. Unfortunately, this intervention is frequently inaccessible to patients.
Remote rehabilitation and monitoring of patient’s vital signs (e.g., heart rate) are potentially valuable mechanisms to improve patient care and access, especially in rural areas. However, further research is needed to assess the effect and practicality of delivering PR programs using telerehabilitation and telemonitoring.
This study aims to evaluate the effects of a pulmonary telerehabilitation program that incorporates telemonitoring on patients with chronic lung diseases. It also aims to assess the feasibility of using videoconference and commercial wearable devices in patient treatment.
In this study, 24 patients with chronic obstructive pulmonary disease and/or pulmonary fibrosis will participate in a pulmonary telerehabilitation program involving group exercise and education sessions via videoconference.
Heart rate, blood oxygen level and physical activity will be monitored using a smart watch and a finger pulse oximeter connected to a smart phone or tablet. We anticipate that people will experience improvement in their health outcomes and be satisfied with receiving the intervention in the comfort of their home.
Additionally, results of this study will guide the planning and development of alternative formats for PR programs in Manitoba, which could improve access to this much-needed service, especially for patients with mobility difficulties and patients who live outside Winnipeg.
Dr. Rene Zahedi
Improved prediction of subclinical and early clinical kidney transplant rejection by a CXCL10 isoform specific mass spectrometry assay
More than 40,000 Canadians have end-stage kidney disease (ESKD). Approximately 60 per cent of these undergo dialysis. The cost of dialysis can reach $200,000 per patient per year in remote areas of Manitoba and amounts to over $2 billion per year in Canada.
Nevertheless, approximately 50 per cent of these patients typically die within four years. Kidney transplantation improves ESKD patient survival and quality of life and reduces costs. Unfortunately, one in three patients will experience transplant rejection within a year, leading to a considerably reduced survival rate.
Although early detection and early treatment can dramatically reduce the risk of rejection and death, current clinical testing fails to detect rejection early enough. Therefore, we are investigating whether a specific molecule in urine, the protein CXCL10, enables early detection of rejection and can predict outcomes.
CXCL10 urine levels are clearly higher in patients with transplant rejection, allowing not only early detection but also personalized treatment. However, predictions made based on the currently available testing method are often not accurate. A probable reason is that these tests cannot distinguish between different forms of the CXLC10 protein. Although these different forms are almost identical, they have very different effects – some of them may accelerate rejection, while others may slow it down.
We will develop a more specific test to clearly distinguish these different forms of urinary CXCL10 and thus improve its diagnostic value for transplant patients. Ultimately, this will enable more personalized patient treatment to yield better outcomes, higher survival rates and a better quality of life, while reducing costs.
The Manitoba Medical Service Foundation has been awarding research grants since 1971. The Foundation has granted millions of dollars to Manitobans for health research and education throughout the province.
To view a listing of past recipients, please reference our book, A Legacy of Advancing Health Research or previous MMSF brochures. Please note that brochures have been discontinued as of 2021.
The Manitoba Medical Service Foundation has been awarding research grants since 1971. The Foundation has granted millions of dollars to Manitobans for health research and education throughout the province.
To view a listing of past recipients, please reference our book, A Legacy of Advancing Health Research or previous MMSF brochures. Please note that brochures have been discontinued as of 2021.