These training awards will support health researcher training to build capacity in the future of T1D research.
CIRTN was established in 2020 as a world-class training and research network with joint contributions from the University of Alberta, University of British Columbia, University of Manitoba, Université de Montréal, Institut de Recherches Cliniques de Montréal, and the University of Toronto and now includes 12 institutions from across Canada.
Now, in 2023, JDRF Canada has partnered with CIRTN to leverage funding to this network from the National Science and Engineering Research Council – Collaborative Research and Training Experience (NSERC-CREATE) program. Through this partnership, JDRF Canada is pleased to fund 6 PhD trainee scholarships and 1 postdoctoral fellowship to trainees working on pancreatic islet research. This support is part of JDRF’s goal to expand its support of the next generation of T1D researchers in 2023 and beyond.
Angeles Olvera, Zuraya Elisa
Vincent Poitout, Université de Montréal
Mechanisms controlling beta cell proliferation by nutrients
Beta cells located within the pancreas are responsible for the production and secretion of insulin. T1D is caused by the destruction of beta cells by the body’s own immune response, whereas type 2 diabetes involves eventual loss of beta cell function. This research will examine how oleate (a fatty acid naturally occurring in animal and vegetable fats and oils) contributes to increasing the growth of beta cells. Specifically, the relationship between reactive oxidative species and antioxidant enzymes produced by the beta cells will be examined to determine its role in beta cell proliferation.
Jonathan Rocheleau, University of Toronto
Design of an islet-on-a-chip device to dynamically measure 1st-phase oxygen consumption rate and insulin secretion from individual islets
The measurement of insulin secretion and oxygen consumption rate by islets is important for characterizing glucose metabolism in people with diabetes. This research project will design an “islet-on-a-chip” – that is, a living islet stabilized inside a microfluidic chip – for the purpose of measuring insulin secretion and oxygen consumption from individual islets simultaneously. These devices will then be used to evaluate the impact of metabolic stresses on islets during glucose metabolism, providing new information about islet cell molecular function.
Bruce Verchere, University of British Columbia
Mitigating amyloid associated islet transplant failure with pramlintide-expressing human embryonic stem cell derived beta cells
Transplantation of insulin-producing beta cells is a potential curative therapy for T1D; however, limited organ donors, the need for lifelong immune suppression, and the eventual failure of transplanted cells hinder widespread clinical implementation. One cause of islet transplant failure is the formation of toxic protein aggregates called amyloid. Therefore, this research will examine the use of beta cells from genetically engineered embryonic stem cells. Specifically, these cells will be engineered to produce Pramlintide, which does not form amyloid, and assessed to determine whether the inhibition of amyloid formation could enhance transplant survival and function.
Bruce Verchere, University of British Columbia
Characterizing human islet-resident macrophages in health and disease
Macrophages are innate immune cells that can alter their function based on their surrounding environment. In mice pancreas, islet macrophages play an important role in development and proliferation of insulin-producing beta cells, and thus are a potential target for diabetes therapy. This research project will analyze human islet macrophages to provide new insight into their function in T1D as well as the communication between macrophages and beta cells.
Gareth Lim, University of Montreal/CRCHUM
Development of a screening approach to repurpose previously approved drugs to ameliorate Type I Diabetes
Autoreactive CD8+ T cells are the cells responsible for the selective destruction of insulin-producing beta cells in T1D. The survival of CD8+ T cells is controlled through specific protein-protein interactions. This research will identify compounds that can disrupt these protein-protein interactions – leading to destruction of the harmful CD8+ T cells. Small molecules that have destructive effects on CD8+ T cells may be a promising therapy for the delay or prevention of T1D with the additional benefits from small molecule drugs such as oral administration and lower cost as compared to existing therapies that target T cells.
Michael Riddell, York University
The role of somatostatin in the deficient glucagon response to acute and recurrent hypoglycemia
Glucagon is a pancreatic hormone that stimulates the liver to release stored glucose in response to low blood glucose levels as a counter-regulator to insulin, meaning that these two hormones work together to balance blood sugar. Somatostatin inhibits the release of insulin and glucagon, thus, blocking the action of somatostatin may help to prevent hypoglycemia in people with diabetes. ZT-01 is one such drug that acts in this way (i.e., a somatostatin receptor antagonist) and is now being tested in clinical trials for its ability to prevent lows in people with T1D by Canadian company Zucara Therapeutics. This project will delve further into the pathways affected by ZT-01 by studying somatostatin at low glucose levels in rodent models of type 2 diabetes, which will in turn help to inform and advance the ZT-01 development program.
Jean Buteau, University of Alberta
A novel small-molecule activator of Lyn kinase for the treatment of type 1 diabetes
Although people living with T1D have a substantial >80% loss of insulin-producing beta cell mass, there is evidence that most people with long-duration T1D still have surviving beta cells and secrete small amounts of insulin. Therefore, approaches that preserve residual beta cells and stimulate beta cell expansion may be a promising therapy for T1D. This research will examine a small molecule activator of Lyn – a novel regulator of beta cell “health”. Through pharmacological activation of Lyn, it is hypothesized that surviving beta cells will be preserved, and beta cell mass expansion will be promoted. This research will have significant implications for clinical therapies to harness existing insulin-producing beta cells in T1D.