Category Archives: Lung Injury and Infection

Lung Injury and Infection Theme: The respiratory system is exposed to many environmental insults throughout life that can result in acute or chronic injury to the lungs. Both infectious and non-infectious agents can trigger inflammation, which is essential to combat infections but also requires exquisite regulation to avoid counterproductive lung damage. In addition to major respiratory pathogens such as tuberculosis (TB), dysregulated inflammation triggered by bacteria and viruses is a major contributing factor to numerous respiratory diseases (e.g., cystic fibrosis, chronic obstructive pulmonary disease). This theme investigates the key molecular signaling pathways underlying pulmonary inflammation under these conditions, with the goal of developing new targeted therapies and biomarkers predictive of disease responses. Our researchers are also leaders in the performance of large-scale diagnostic and treatment studies involving patients infected with TB.

Major scientific objectives for the lung injury and infection theme include: (1) Identify the key molecular effectors of innate and adaptive immunity required for an integrated response to respiratory pathogens such as influenza, TB, and cryptococcus neoformans. (2) Dissect host-pathogen interactions driving chronic infections versus acute infectious pulmonary exacerbations in chronic lung diseases (eg. Pseudomonas in cystic fibrosis). (3) Investigate the molecular underpinnings of beneficial versus pathological responses by different components of lung mucosal immunity. (4) Explore the mechanistic links between cellular metabolism and fibrogenic processes in the lung.

View posts, news, and publications related to this research theme below.

Opinion: All levels of government must take decisive, co-ordinated action now before it's too late opinion piece by salman qureshi and colleagues from the critical care network

Stepping up to COVID-19

Read the opinion piece co-written by Dr. Faiz Ahmad Khan in the Hill Times – published March 25, 2020 here:

With the arrival of COVID-19, Canada’s health-care system is being tested as never before. Canadian leaders must elicit the assistance of private industry to ensure its continued success, as health-care supplies and equipment are rapidly depleted. A substantial increase in testing for the virus together with significant financial investments in research, aimed at a deeper understanding of the virus and development of a vaccine, should also be top priorities. Solid financial support for all those impacted by the virus will ensure a rapid return to normal once the crisis has abated. Maintaining open communication and collaboration between leaders, the government, and with partners across the board is the key to our ultimate success.

Opinion piece by Salman Qureshi and colleagues from the Critical Care Infectious Disease Network in Canada: All levels of government must take decisive, co-ordinated action now before it's too late

COVID-19 Need for coordinated action

Dr. Salman Qureshi and colleagues from the Critical Care – Infectious Diseases Network in Canada speak to the critical actions needed as we experience this public health crisis.

Read the full new article in the National Post published on March 17, 2020 here:

Canadian leaders can reduce the damage caused by COVID-19 to Canadians and Canadian society by paying close attention to decisions taken in countries currently experiencing severe outbreaks. Strategies to mitigate the spread of the virus amongst the population, minimizing the strain of our healthcare system at any one time, coupled with a sharing of resources across boundaries as the demand for health-care fluctuates, will together play an important role on the ultimate long-term effect of this virus on our society.

Funding from Bill and Melinda Gates Foundation to Maziar Divangahi at the Meakins-Christie Laboratories

Grant to investigate HSCs & innate immunity

Congratulations to Maziar Divangahi for his new grant from the Bill & Melinda Gates Foundation. The project will investigate the impact of beta glucan on hematopoietic stem cells (HSCs) and innate immunity.

Project title: Beta-glucan induced trained innate immunity.

Maziar Divangahi is a faculty member at McGill University and the Meakins-Christie Laboratories and scientist within the RI-MUHC Respiratory Program.

Faiz Ahmad Khan was funded through the OBCIA program for his innovative tuberculosis research program that will examine the impact of artificial-intelligence based tools for diagnosing tuberculosis

OBVIA funds innovative AI program

Congratulations Faiz Ahmad Khan! The project submitted by his team has just been awarded funding by l’Observatoire International sur les impacts sociétaux de l’IA et du numérique (OBVIA). OBVIA is supported by the FRQS. It aims to support communities, organizations, and individuals to maximize the benefits of artificial intelligence (AI) and digital health technologies. As part of the fist call for research proposals, funded projects will examine the societal impacts of AI and digital health.

Faiz’s project was ranked 1st and is among the first projects funded through this innovative competition. Congratulations Faiz! Using tuberculosis as an example, the study will evaluate the effectiveness and impact of diagnostic tools based on artificial intelligence to see how they influence health equity.

Project title.
AI “solutions” to global health challenges: an inter-disciplinary case study to critically evaluate the development and implementation of an artificial-intelligence based tool for diagnosing tuberculosis, the world’s leading infectious killer.

Team Members: Faiz Ahmad Khan (McGill University), Pierre-Marie David (Université de Montréal) and Sabaa Khan (University of Eastern Finland, School of Law).

Read the entire Press Release here

Faiz Ahmad Khan is an Associate member of the Meakins-Christie Laboratories and a Junior Scientist within the RI-MUHC Respiratory Program.

Scientists-from-McGill-University-and-the-Research-Institute-of-the-MUHC-visit-Braunschweig

Meakins faculty delegation to Braunschweig

Six members of the RI-MUHC took part in a delegation to the Helmholtz Centre for Infection Research (HZI) in Braunschweig. Among them were Drs. Irah King, Dao Nguyen, and Maziar Divangahi.

The delegation was part of working visit by McGill University and the McGill Interdisciplinary Initiative in Infection and Immunity (MI4). Presentations were on selected research topics related to infection including global health, the role of microbiota in infections and personalized medicine.

Read more here on the RI-MUHC News and McGill News websites:

The World Health Organization (WHO) Global TB Programme and the WHO Collaborating Centre in TB Research at McGill University, Montreal, Canada convened a two-day technical consultation on research on latent TB infection

Research on Latent TB Infection

Technical consultation on latent TB infection management: Research for scale-up and target regimen profiles.

The World Health Organization (WHO) Global TB Programme and the WHO Collaborating Centre in TB Research at McGill University, convened a two-day technical consultation on research on latent TB infection.

The first day of the meeting focused on research needs to overcome key barriers and knowledge gaps affecting the scale-up of TB preventive treatment. Experts reviewed recent advances in diagnosis and treatment of LTBI and shared implementation experience generated over the past 5 years. A revised priority list of research topics was discussed, covering diagnosis, treatment and implementation research. 

Dr. Dick Menzies was interviewed. Dr. Menzies is a RESP Program member and an Associate Member of the Meakins-Christie Laboratories was interviewed. His research focuses on clinical and epidemiologic aspects of tuberculosis. His clinical research involves diagnosis of latent as well as active TB.

Read more here.

Dragonfly wings are naturally antibacterial - article with Dao Nguyen

Dragonfly wings in the hospital

Did you know that dragonfly wings are naturally antibacterial?

Biofilms are colonies of bacteria that can attach securely to the surface of certain medical devices. Shockingly, a quarter of all nosocomial infections are reported to be associated with the use of infected equipment, based on American data.

RI-MUHC researcher Dao Nguyen shares some thoughts on combatting biofilms in this short article from Quebec Science. Her research team is looking at the wings of dragonflies and cicadas to better design safe antibacterial materials. Nanometric structures on dragaonfly and cicada wings actually kill bacteria by physical contact. Therefore, there is great interest to design and develop antibacterial materials that mimic this natural structure.

The research team will observe interactions between bacteria and these newly designed materials, then test the most promising against Pseudomonas aeruginosa. Pseudomonas aeruginosa is a bacteria responsible for hospital-acquired infections as well as fatal infections in people with cystic fibrosis. It has an ability to form biofilms and is naturally resistant to many drugs.

If the results are conclusive, the materials may eventually be used on a large scale to make safer medical devices and instruments.

Read the full article here (in French).

respiratory research grant results at the meakins-christie laboratories

Funding News – CIHR Project Grant

Congratulations to the following Spring 2019 Project Grant Recipients

Dr. Sushmita Pamidi received funding for her project co-led with Evelyn Constantin (CHHD program) entitled “Maternal sleep-disordered breathing during pregnancy and long-term health outcomes in children: the 3D pregnancy and birth cohort”. Dr. John Kimoff is a co-investigator on the grant.

Dr. Larry Lands is a co-applicant with Dr. Michael Parkins (University of Calgary) for the grant entitled “The influence of Cytomegalovirus infection on cystic fibrosis disease progression”.

View full CIHR Funding Decisions for the 2019 Spring Project Grant Competition.

Dorival Martins Relève étoile Jacques-Genest

Dr. Dorival Martins receives the Relève étoile Jacques-Genest Award

Congratulations to Dorival Martins Jr, postdoctoral fellow in Biochemistry, McGill University (supervisor: Dr. Dao Nguyen) for his Relève étoile Jacques-Genest award from the Fonds de recherche du Québec (FRQ) for the month of July.

Winning article: Martins D, McKay G, Sampathkumar G, Khakimova M, English AM, Nguyen D. Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences. 2018 Sep 25;115(39):9797-9802. doi: 10.1073/pnas.1804525115. Epub 2018 Sep 10. PMID: 30201715

Read the full news release here.

Dr. Erwan Pernet and Dr. Maziar Divangahi, scientists at the RI-MUHC and the Meakins-Christie Laboratories have identified a lipid target to tone down the hyper-active immunity to influenze infection

Flu treatment using lipid target

Dr. Maziar Divangahi and his postdoctoral fellow Dr. Erwan Pernet are on a promising path towards developing flu treatment using a lipid target. They identified a new role for the lipid mediator Leukotriene B4 in the lung. In a study published in Nature Microbiology, they show that the LTB4 molecule is capable of not only reducing collateral tissue damage caused by immune responses but also enhancing host survival.

“The influenza virus is not the only threat; the host’s own immune response is mainly responsible for jeopardizing host survival. Therefore, it is essential to understand the regulatory mechanisms that maintain the tight balance between protective and harmful immunity.”

– Erwan Pernet

Influenza remains a global public health challenge, according to the World Health Organization. Each year, there are an estimated one billion people cases worldwide, resulting in 290,000 to 650,000 influenza-related respiratory deaths.

Dr. Divangahi’s laboratory has focused on new immunotherapies targeting the immune system via host lipid mediators to either effectively kill the virus or limit lung tissue damage. In this study, they focused on the LTB4 lipid mediator and its effects on the immune response to flu infection. After working with mice lacking the receptor for LTB4, they were able to identify a network of regulatory mechanisms that maintain the tight balance between protective and harmful immunity. Also, of particular importance to future clinical studies was the finding that a single dose of LTB4 at the peak of disease was enough to significantly reduce lung immunopathology and tissue damage and improve host survival. 

“For the first time we show there is a subtype of macrophages in the lungs that are able to produce this immunoregulatory lipid (LTB4) to reduce the inflammation caused by another macrophage population that is responsible for causing lung tissue damage during influenza infection.”

– Maziar Divangahi

View the full publication here:

Leukotriene B4-type I interferon axis regulates macrophage-mediated disease tolerance to influenza infection. Pernet E, Downey J, Vinh DC, Powell WS, Divangahi M. Nat Microbiol. 2019 May 20. doi: 10.1038/s41564-019-0444-3. PMID: 31110361

The research was also featured in the CIHR-III (institute of Infection and Immunity) newsletter!

View articles and interviews about this research: