RI-MUHC Annual Report

RI-MUHC ANNUAL REPORT 2023

YEAR IN REVIEW

METABOLIC DISORDERS AND COMPLICATIONS (MeDiC) PROGRAM

RESEARCH HIGHLIGHTS

The German-Canadian consortium, NephroCAGE, aims to demonstrate the added value of artificial intelligence and federated learning in kidney transplantation.

Extending kidney graft survival, thanks to precision medicine tools

The German-Canadian consortium NephroCAGE uses artificial intelligence and federated learning to develop better predictive models to identify patients at risk for graft rejection. The project will yield new knowledge to help improve decisions on the allocation of kidneys, carrying the promise of extending graft survival, thanks to precision medicine tools for epitope matching and personalized immunosuppression regimens.

Dr. Ruth Sapir-Pichhadze and Dr. David Buckeridge, two researchers from the Metabolic Disorders and Complications (MeDiC) Program at the Research Institute of the McGill University Health Centre (RI-MUHC), are co-investigators of NephroCAGE, joining team members from the RI-MUHC, MUHC, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), University of British Columbia, CHARITÉ and PIRCHE. The project is funded by the Ministère de l'Économie et de l'Innovation et de l’Énergie (Quebec), Kidney Foundation of Canada, Canadian Institutes for Health Research (CIHR), McGill University Health Centre Foundation, MI4 (McGill University) and Paladin.

RESET for remission – reversing type 2 diabetes

The “RESET for remission” study is a joint Canada-UK project funded by CIHR as part of the 100 Years of Insulin: Accelerating Canadian Discoveries to Defeat Diabetes program, and by the Medical Research Council of the United Kingdom. The randomized clinical trial aims to help people 18 to 45 years old with type 2 diabetes reverse this condition with a structured, supervised exercise strategy combined with a low-energy, partial meal replacement diet. Team members are from the RI-MUHC, University of Alberta and Leicester Diabetes Centre. The study lead, MeDiC Program researcher Dr. Kaberi Dasgupta, aims to reverse the rising incidence rate of diabetes diagnosis both by advancing research and by working with policymakers.

Health Impacts of Inactivity Study

The Health Impacts of Inactivity Study funded by CIHR, in partnership with the Canadian Frailty Network and the Canadian Space Agency, aims to look at the effects of inactivity on the human body and the effectiveness of a countermeasure, physical exercise. The Health Impacts of Inactivity Study sets the stage for the realization of bed rest studies using state-of-the-art infrastructure at the RI-MUHC’s Centre for Innovative Medicine. These studies build on research collaborations between the RI-MUHC, CRCHUM, and eight research teams from institutions across Canada. MeDiC Program researcher Tyler Churchward-Venne, PhD, leads the Best Rest Study team within this framework.

At left: Dr. Kaberi Dasgupta (third from left) introduced the RESET study and other key clinical trials focused on diabetes to Member of Parliament Sonia Sidhu, Chair of the All-Party Diabetes Caucus (first from left), who visited the RI-MUHC in November 2022. At right: Members of the Best Rest Study Team led by Tyler Churchward-Venne, PhD (far right).

Selected MeDiC Program news links

SELECTED PUBLICATIONS

Haidar, A., Lovblom, L. E., Cardinez, N., Gouchie-Provencher, N., Orszag, A., Tsoukas, M. A., Falappa, C. M., Jafar, A., Ghanbari, M., Eldelekli, D., Rutkowski, J., Yale, J. F., & Perkins, B. A. (2022). Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 × 2 factorial randomized crossover trial. Nature medicine, 28(6), 1269–1276. doi: 10.1038/s41591-022-01805-3

Suri, R. S., Lee, J. Y., Ban, M. R., Shrum, B., Tutunea-Fatan, E., Ismail, O. Z., Leckie, S. H., McIntyre, A. D., Xu, Q., Lee, S. H., de Chickera, S. N., Hegele, R. A., & Gunaratnam, L. (2022). Defective KIM-1 phagocytosis does not predispose to acute graft dysfunction after kidney transplantation in humans. Kidney international, 102(2), 435–439. doi: 10.1016/j.kint.2022.05.006

Sonja K. Soo, Annika Traa, Zenith D. Rudich, Alibek Moldakozhayev, Meeta Mistry, Jeremy M. Van Raamsdonk. Genetic basis of enhanced stress resistance in long-lived mutants highlights key role of innate immunity in determining longevity: Aging Cell 22(2):0, 2023: doi: 10.1111/acel.13740

Caterina Facchin, Anne Laure Larroque, A. Alliaga, Ana B. Fraga-Timiraos, Bertrand Jean-Claude. Superior efficacy of a dual EGFR-DNA targeting combi-molecule “ZR2002” in comparison with its analogues 6-mono-alkylamino- and 6,6-dialkylaminoquinazoline in a human osteosarcoma xenograft model: European Journal of Cancer 174(0):0, 2022: doi: 10.1016/S0959-8049(22)00845-0

José Refugio Navarro-Betancourt, Joan Papillon, Julie Guillemette, Chenfang Chung, Takao Iwawaki, Andrey V.E. Cybulsky. The unfolded protein response transducer IRE1α promotes reticulophagy in podocytes: Biochimica et Biophysica Acta - Molecular Basis of Disease 1868(6):0, 2022: doi: 10.1016/j.bbadis.2022.166391

Tessier, A. J., Wing, S. S., Rahme, E., Morais, J. A., & Chevalier, S. (2022). Association of Low Muscle Mass With Cognitive Function During a 3-Year Follow-up Among Adults Aged 65 to 86 Years in the Canadian Longitudinal Study on Aging. JAMA network open, 5(7), e2219926. doi: 10.1001/jamanetworkopen.2022.19926

William Lemieux, David Fleischer, Archer Yi Yang, Matthias Niemann, Karim Oualkacha, William Klement, Lucie Richard, Constantin Polychronakos, Robert Stefan Liwski, Frans H.J. Claas, Howard M. Gebel, Paul A. Keown, Antoine Lewin, Ruth Sapir-Pichhadze. Dissecting the impact of molecular T-cell HLA mismatches in kidney transplant failure: A retrospective cohort study: Frontiers in Immunology 13(0):0, 2022: doi: 10.3389/fimmu.2022.1067075

Ali Mehdi, Mikhaël Attias, Ani Arakelian, Moshe Szyf, Ciriaco A. Piccirillo, Shafaat Ahmed Rabbani. S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas: Neoplasia (United States) 36(0):0, 2023: doi: 10.1016/j.neo.2022.100874

İçten Meraş, Laëtitia Chotard, Thomas Liontis, Zakaria Ratemi, Benjamin Wiles, Jung-hwa Seo, Jeremy M. Van Raamsdonk, Christian E. Rocheleau. The Rab GTPase activating protein TBC-2 regulates endosomal localization of DAF-16 FOXO and lifespan: PLoS Genetics 18(8):0, 2022: doi: 10.1371/journal.pgen.1010328

Dana Sedki, Aaron Cho, Yubo Cao, Ljiljana Nikolajev, N. D.Prasad Atmuri, William D. Lubell, Stéphane A. Laporte. Prostaglandin F2α and angiotensin II type 1 receptors exhibit differential cognate G protein coupling regulation: Journal of Biological Chemistry 298(9):0, 2022: doi: 10.1016/j.jbc.2022.102294

Hassanabadi, N., Berger, C., Papaioannou, A., Cheung, A. M., Rahme, E., Leslie, W. D., Goltzman, D., & Morin, S. N. (2023). Variation in bone mineral density and fractures over 20 years among Canadians: a comparison of the Canadian Multicenter Osteoporosis Study and the Canadian Longitudinal Study on Aging. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 34(2), 357–367. doi: 10.1007/s00198-022-06623-4

Sandal, S., Ahn, J. B., Cantarovich, M., Chu, N. M., Segev, D. L., & McAdams-DeMarco, M. A. (2022). Evolving Trends in Risk Profiles and Outcomes in Older Adults Undergoing Kidney Retransplantation. Transplantation, 106(5), 1051–1060. doi: 10.1097/TP.0000000000003842