FoMD researchers receive $13.7 million from CIHR

New project grants helping to push frontiers of knowledge

Ryan O'Byrne - 23 March 2021

The Canadian Institutes of Health Research has awarded a total of $13.7 million to nine projects led by Faculty of Medicine & Dentistry researchers as part of its latest round of project grant research funding. The projects range from new cryopreservation techniques for organs to understanding and addressing HPV vaccination hesitancy in Arctic Canadian Indigenous communities.

Three of the funded projects are directly related to COVID-19, as announced March 12 by Patty Hajdu, Canada’s minister of health. In total, 19 projects at the University of Alberta were granted funding from CIHR in this round.

CIHR-funded FoMD projects

Jason Acker - Enabling liver cryopreservation by controlling ice recrystallization with small molecule inhibitors

“Currently, human organs can only be stored outside the body for several hours under carefully controlled conditions, which makes the supply of tissues and organs one of the single largest problems currently facing modern medicine," said Jason Acker, professor in the Department of Laboratory Medicine and Pathology. “However, advances in subzero storage of machine-perfused organs has created the possibility of establishing organ cryobanks that could help make more organs available for transplantation.”

Thanks to the CIHR project grant, Acker’s team is investigating partial freezing as a strategy for extending the storage time of organs prior to transplant, using a nature-inspired approach to control the growth of ice crystals. The group has developed synthetic, small-molecule ice-recrystallization inhibitors, which function to control both extra- and intracellular ice-crystal growth, an approach similar to strategies used in nature by some organisms to survive freezing in the winter. Acker’s team aims to develop new insights into how these ice-control agents function to protect cells and tissues from freezing injury, and will explore their use in the low-temperature preservation of whole organs prior to transplantation.


Shokrollah Elahi - Deciphering immune responses in COVID-19 patients to identify immune correlates of protection and susceptibility for targeted therapeutics

Despite the substantial work done to understand COVID-19, there are still several unanswered questions about the impacts the virus has on the immune system. With the CIHR funding, Shokrollah Elahi’s team plans to conduct a comprehensive study at the cellular and molecular levels in COVID-19 patients with asymptomatic, mild, moderate, severe and critical symptoms of the disease. Over the next three years, the team is hoping to gain a thorough understanding of all the immune responses associated with SARS-CoV-2, especially in high-risk groups. This knowledge will be fundamental to informing public-health policies needed to limit disease spread and protect high-risk groups in the future.


Grant Innes (U of C), with Jake Hayward and Rhonda Rosychuk (U of A) - Impact of Emergency Department Opioid Prescribing on Health Outcomes

In a joint project between the University of Calgary and U of A, Grant Innes’s team will study patients who received an opioid prescription during their emergency department (ED) visit to determine how many go on to become long-term users or experience adverse outcomes, such as death, overdose or hospitalization related to opioid use. They will determine which patients are most likely to experience problems related to their prescription, such as those who are older or with specific types of illnesses or injuries. Finally, they will investigate whether patients who show evidence of opioid-use disorder before visiting the ED are safer when they get an opioid versus non-opioid medication for acute pain. Ultimately, the team believes this research will help doctors and patients decide how risky an opioid prescription is and if it is safe to use these drugs to treat pain in the ED.


Allan Murray - Repair in Transplant Vasculopathy

Allan Murray’s group was the first to identify that the repair molecule apelin played a major role in protecting against vascular disease following a heart transplant. Now, the team is looking to understand the repair response undertaken by the endothelial cells that line the blood vessels of a transplanted heart, focusing on apelin. They hope to determine if the administration of apelin reduces the narrowing of the major arteries in a heart transplant model and study in detail the vascular repair response. Ultimately, the team is looking to bring any advances in diagnostics and therapeutics that arise from this work into the clinic.


Vivian Mushahwar - Spinal Neuromodulation for Restoring Function after Neural Injury or Disease

Continuing her groundbreaking work on restoring motor functions following a spinal cord injury, Vivian Mushahwar and team will explore two paradigms of spinal cord stimulation that have shown great potential—epidural spinal cord stimulation (ESCS) and intraspinal microstimulation (ISMS). Though exactly how each of these paradigms work is still unknown, exciting new results suggest that ESCS, coupled with extensive physical therapy, may restore some ability to walk for people with severe spinal cord injury. While more invasive, ISMS appears to produce substantially further walking distances—upwards of one kilometre—in animal models. The results of this pivotal study will be crucial for determining the suitability of ESCS and ISMS for restoring meaningful distances of walking after severe spinal cord injury, and will guide how these stimulation strategies may be used with patients in the future.


Gavin Oudit - Pathogenesis of COVID-19 mediated Cardiovascular Complications: Therapeutic Applications

Gavin Oudit and team have proposed a comprehensive study examining the link between COVID-19 and cardiovascular disease through the lens of a variety of cells, from in-vitro cell culture, to preclinical animal model, to heart specimens and plasma from patients on the full spectrum of disease severity. The team will try to determine if the levels of certain enzymes linked to cardiovascular function—specifically ACE2 or ADAM17—can be used as biomarkers for cardiovascular complications in response to COVID-19. From this, the team will investigate whether manipulating ADAM17 or ACE2 could protect against the exacerbation of cardiovascular complications in these patients.


Sangita Sharma - Assessing attitudes, barriers, and opportunities for human papillomavirus (HPV) vaccination (HPVV) to inform, develop, implement, and evaluate a culturally appropriate program for increasing utilization and addressing vaccination hesitancy in Arctic Canadian Indigenous communities

In partnership with two Northwest Territories Indigenous communities, Hotıì ts’eeda Northwest Territories SPOR Unit, and the Government of Northwest Territories’ Department of Health and Social Services, Sangita Sharma’s project will listen to people’s experiences and concerns surrounding HPV, HPV vaccination and vaccine hesitancy within the context of COVID-19 using Indigenous methodologies including “Two-Eyed Seeing.” The project will develop, implement and evaluate a culturally safe, community-based program, designed and delivered by local staff. It will utilize on-the-land and traditional activities to understand and address concerns related to cervical cancer and HPV/COVID-19 vaccine hesitancy. The project aims to increase HPV vaccination and ultimately reduce the burden of HPV-related cancers.


Simonetta Sipione - The role of glycosphingolipids in the secretion and clearance of extracellular vesicles in brain health and disease

Gangliosides are sugar-lipid molecules in the brain that play important roles in the communication among cells. During aging and in certain neurodegenerative diseases, such as Parkinson’s disease and Huntington's disease, levels of gangliosides decrease. Simonetta Sipione's team has shown that administration of the ganglioside GM1 has great therapeutic effects in mouse models of Huntington's disease which, like Alzheimer's disease and Parkinson's disease, is caused by the accumulation of a toxic protein in the brain. With the CIHR funding, Sipione’s team will investigate the underlying mechanisms of how GM1 affects the communication between brain cells and cellular disposal of toxic proteins. The project will help determine whether GM1 or similar molecules could be a novel treatment not only for Huntington’s disease, but also potentially for Alzheimer’s disease and Parkinson’s disease.


Harissios Vliagoftis - Proteinase-Activated Receptor-2 Agonists as Adjuvants for Mucosal Vaccination

"We know that one way to decrease infections and death from the flu virus is to vaccinate people, and most vaccines are given by injection into muscles," said Harissios Vliagoftis, professor in the Department of Medicine. "The cost for administration of these vaccines is high because in addition to the production cost, they require medical personnel to administer. So there is a lot of interest to develop vaccines that we can give into the nose, because administration is easier and less traumatic, and they have the potential to be more effective for respiratory infections."

One barrier to nasal vaccines, however, is that they require specialized "mucosal adjuvants," compounds in short supply that help stimulate the immune system to respond to the vaccine. Vliagoftis and his team, which includes Kevin Kane from the Department of Medical Microbiology & Immunology, have identified a compound—a small molecule that triggers a cell surface structure called Proteinase-Activated Receptor-2 (PAR-2)—that can work as an adjuvant for a nasal flu vaccine. With the funding from CIHR, Vliagoftis’ team will study the ability of this molecule to function as an adjuvant for flu vaccination in mice models. This will be the first time this compound has been studied for this purpose.


Toshifumi Yokota - Development of Antisense Oligonucleotide-Based Therapy for Facioscapulohumeral Muscular Dystrophy

Toshifumi Yokota’s research aims to develop a new treatment for facioscapulohumeral muscular dystrophy (FSHD), which is caused by the abnormal production of a protein called DUX4 in muscle cells. There is currently no cure for the disease. The team plans to use small DNA-like molecules called gapmers to find and destroy the gene products responsible for making DUX4 in mouse models and decrease the amount of the protein in muscle cells. The ultimate goal will be to identify a possible gapmer that can be tested in clinical trials for treating FSHD in humans, which could lead to a new therapy to improve the lives of people with the disease.