RI-MUHC Annual Report

RI-MUHC ANNUAL REPORT 2023

YEAR IN REVIEW

TRANSLATIONAL RESEARCH IN RESPIRATORY DISEASES (RESP) PROGRAM

RESEARCH HIGHLIGHTS

Ben Smith, MD, Jun Ding, PhD, and Larry Lands, MD, PhD (top, left to right), are combining their expertise to regenerate damaged lungs; Dao Nguyen, MD (bottom left), heads a facility tackling antimicrobial resistance, a major global health threat.

Regenerating damaged lungs: Landmark research toward a cure for COPD

Dr. Ben Smith, Dr. Larry Lands and Jun Ding, PhD, three researchers from the Translational Research in Respiratory Diseases (RESP) Program at the Research Institute of the McGill University Health Centre (RI-MUHC), received the prestigious RI-MUHC Trottier Webster Innovation Award in 2023. The team will combine their expertise in airways disease, machine learning and nanoparticles to conduct a pioneering study. Using mRNA therapies delivered with lipid nanoparticles, their project will determine whether airway stem cells in chronic obstructive pulmonary disease (COPD) that exhibit signs of “exhaustion” can be reprogrammed into a more functional state.

Overcoming antimicrobial resistance

RESP Program researcher Dr. Dao Nguyen is founder and director of the McGill Antimicrobial Resistance Centre, where RI-MUHC and McGill researchers have joined forces in one of the great scientific challenges of our day. Antimicrobial resistance (AMR) is an urgent and complex problem and one of the top ten global public health threats. Imagine a world where antibiotics no longer work. It is critical for the future of medicine and human health that we find new ways to diagnose, prevent and treat infection. Drawing on expertise across the biomedical, engineering, and animal, natural and social sciences domains, the McGill AMR Centre brings together a diverse scientific community to address AMR challenges and priorities through interdisciplinary research and education – all with the goal of eliminating the emerging threat of antibiotic resistance.

Alveolar macrophages on patrol for respiratory health

In a study published in Nature, RESP Program researchers Maziar Divangahi, PhD, James Martin, MD, and Jun Ding, PhD, collaborated with researchers from McGill University, the University of Calgary and University of Chicago to examine how the lung copes with invading microbes. This impactful publication examined a subset of immune cells called alveolar macrophages, which protect the lung throughout life by patrolling our airways to kill pathogens. The study showed that production of eicosanoids (lipid-based signaling molecules) by neutrophils was required to reprogram alveolar macrophages during early life. In the absence of alveolar macrophage reprogramming by neutrophils, the researchers observed an increased susceptibility to induced acute lung injury, influenza, and SARS-CoV-2 infections. These results highlight the complexity of vital cellular and molecular mechanisms in embryonic development that ensure lung function throughout life.

Lung tissue showing macrophage/neutrophil interaction (left). Authors Erwan Pernet, PhD, a postdoctoral fellow at the time of this study, and his former supervisor, RI-MUHC scientist Maziar Divangahi, PhD (right).

Selected RESP Program news links

SELECTED PUBLICATIONS

Terek Been, Bayan Alakhtar, Hussein Traboulsi, Thupten Tsering, Alexandra Bartolomucci, Nicole Heimbach, Sofia Paoli, Julia Valdemarin Burnier, Koren K. Mann, David H. Eidelman, Carolyn J. Baglole. Chronic low-level JUUL aerosol exposure causes pulmonary immunologic, transcriptomic, and proteomic changes: FASEB Journal 37(2):0, 2023: doi: 10.1096/fj.202201392R

Jean C. Bourbeau, Dany Doiron, Sharmistha Biswas, Benjamin M. Smith, Andrea L. Benedetti, Jeffrey R. Brook, Shawn Aaron, Kenneth R. Chapman, Paul Hernández, F́rançois Maltais, Darcy D. Marciniuk, Denis Einan O'Donnell, Donald D. Sin, Brandie L. Walker, Liesel Dsilva, Gilbert Nadeau, Valérie Coats, Chris Compton, Bruce E Miller, Wan C Tan. Ambient Air Pollution and Dysanapsis: Associations with Lung Function and Chronic Obstructive Pulmonary Disease in the Canadian Cohort Obstructive Lung Disease Study: American Journal of Respiratory and Critical Care Medicine 206(1): 44-55, 2022: doi: 10.1164/rccm.202106-1439OC

Annie-Claude Jalbert, Lyna Siafa, Agnihotram V Ramanakumar, Deborah Assayag. Gender and racial equity in clinical research for idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Eur Respir J. 2022 Mar 3;59(3): 2102969. doi: 10.1183/13993003.02969-2021

Danielle Karo-Atar, Shaida Ouladan, Tanvi Javkar, Loïck Joumier, Macy K. Matheson, Sydney Merritt, Susan Westfall, Annie Rochette, Maria E. Gentile, Ghislaine Fontés, Gregory Joseph Fonseca, Marc Parisien, Luda B. Diatchenko, Jakob Von-Moltke, Mohan Malleshaiah, Alex Gregorieff, Irah L King. Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity: Journal of Experimental Medicine 219(9):0, 2022: doi: 10.1084/jem.20212311

Kelly Kwong, Andrea L. Benedetti, Yvonne C.W. Yau, Valerie J. Waters, Dao Nguyen. Failed Eradication Therapy of New-Onset Pseudomonas aeruginosa Infections in Children with Cystic Fibrosis Is Associated with Bacterial Resistance to Neutrophil Functions: Journal of Infectious Diseases 225(11): 1886-1895, 2022: doi: 10.1093/infdis/jiab102

Jean-Philippe Leduc-Gaudet, Anais Franco-Romero, Marina Cefis, Alaa Moamer, Felipe E Broering, Giulia Milan, Roberta Sartori, Tomer Jordi Chaffer, Maude Dulac, Vincent Marcangeli, Dominique Mayaki, Laurent Huck, Anwar Shams, José A Morais, Elise Duchesne, Hanns Lochmuller, Marco Sandri, Sabah N A Hussain, Gilles Gouspillou. MYTHO is a novel regulator of skeletal muscle autophagy and integrity. Nat Commun. 2023 Mar 2;14(1):1199. doi: 10.1038/s41467-023-36817-1

Vanessa Moarbes, Véronique Gaudreault, Rami Karkout, Lydia Labrie, Hedi Zhao, Jichuan Shan, Elizabeth D. Fixman. STAT6-IP-Dependent Disruption of IL-33-Mediated ILC2 Expansion and Type 2 Innate Immunity in the Murine Lung: Journal of Immunology 209(11): 2192-2202, 2022: doi: 10.4049/jimmunol.2100688

Ntwali Placide Nsengiyumva, Jonathon R. Campbell, Olivia Oxlade, Juan Fernando Vesga, Christian Lienhardt, Anete Trajman, Dennis Falzon, Saskia Den Boon, Nimalan Arinaminpathy, Kevin J. Schwartzman. Scaling up target regimens for tuberculosis preventive treatment in Brazil and South Africa: An analysis of costs and cost-effectiveness: PLoS Medicine 19(6):0, 2022: doi: 10.1371/journal.pmed.1004032

Erwan Pernet, Sarah Sun, Nicole Sarden, Saideep Gona, Angela P. Nguyen, Nargis Khan, Martin Mawhinney, Kim A. Tran, Julia Chronopoulos, Dnyandeo Amberkar, Mina Sadeghi, Alexandre Grant, Shradha Wali, Renaud Prevel, Jun Ding, James G. Martin, Ajitha Thanabalasuriar, Bryan G Yipp, Luis B Barreiro, Maziar Divangahi. Neonatal imprinting of alveolar macrophages via neutrophil-derived 12‑HETE: Nature 614(7948): 530-538, 2023: doi: 10.1038/s41586-022-05660-7

Gamuchirai Tavaziva, Arman Majidulla, Ahsana Nazish, Saima Saeed, Andrea L. Benedetti, Aamir Javed Khan, Faiz Ahmad Khan. Diagnostic accuracy of a commercially available, deep learning-based chest X-ray interpretation software for detecting culture-confirmed pulmonary tuberculosis: International Journal of Infectious Diseases 122(0): 15-20, 2022: doi: 10.1016/j.ijid.2022.05.037

Nicholas Winters, Robert Belknap, Andrea Benedetti, Andrey Borisov, Jonathon R Campbell, Richard E Chaisson, Pei-Chun Chan, Neil Martinson, Payam Nahid, Nigel A Scott, Erin Sizemore, Timothy R Sterling, M Elsa Villarino, Jann-Yuan Wang, Dick Menzies. Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis. Lancet Respir Med. 2023 Mar 23:S2213-2600(23)00096-6. doi: 10.1016/S2213-2600(23)00096-6

Jessica Yu, Filip Morys, Alain A. Dagher, Annie Christine Lajoie, Teresa Gomes, Elena Younhye Ock, R. John Kimoff, Marta Kaminska. Associations between sleep-related symptoms, obesity, cardiometabolic conditions, brain structural alterations and cognition in the UK biobank: Sleep Medicine 103(0): 41-50, 2023: doi: 10.1016/j.sleep.2023.01.023