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.

Pulmonary research group in Canada: the Meakins-Christie Laboratories

Newborn screening for Cystic Fibrosis patients

A new study led by Dr. Larry Lands was recently published in the Journal of Cystic Fibrosis 2016. The study, led by a team from the Research Institute of the McGill University Health Centre (RI-MUHC) and Cystic Fibrosis Canada, reinforces the benefits of newborn screening for Cystic Fibrosis patients. Children with Cystic Fibrosis who are diagnosed through newborn screening are healthier and benefit more from new treatments.

About the study

The study, “The benefits of newborn screening for cystic fibrosis: The Canadian experience” was co-written by D.Y.F. Mak (Cystic Fibrosis Canada, Toronto, Canada), J. Sykes (Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada), A.L. Stephenson (Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada), and L.C. Lands (Research Institute of the McGill University Health Centre, Montreal, Canada).

This work was made possible through the in-kind support from Cystic Fibrosis Canada.

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respiratory research centre in Canada: The Meakins-Christie Laboraotories

Bacteria and Inflammation in Cystic Fibrosis

Dr. Dao Nguyen’s research team discovered that there are variants of Pseudomonas aeruginosa (LasR), a bacteria commonly found in Cystic Fibrosis patients, that can cause a lot of inflammation. The study was published in Science Advances 2015. In some cases, that inflammation leads to the need for lung transplants. Nguyen’s team is the first to make the connection between the bacteria and inflammation. (August 2015)

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flu virus in the airways

PGE2 inhibition increases survival of mice infected with H1N1 flu virus

A study by Dr. Maziar Divangahi revealed that a drug that inhibits PGE2 increases survival of mice infected with H1N1 flu virus. This finding paves the way for urgently needed novel therapies that may be effective against the flu and other viral infections.

“Drugs that specifically target PGE2 pathways have already been developed and tested in animals, so our results have excellent potential for clinical translation, not only for the treatment of influenza, but other viral respiratory infections that interact with similar host immune pathways”.

– Maziar Divangahi

Read the full publication here: Targeted prostaglandin E2 inhibition enhances antiviral immunity through induction of type I interferon and apoptosis in macrophages. Coulombe F, Jaworska J, Verway M, Tzelepis F, Massoud A, Gillard J, Wong G, Kobinger G, Xing Z, Couture C, Joubert P, Fritz JH, Powell WS, Divangahi M. Immunity. 2014 Apr 17;40(4):554-68. doi: 10.1016/j.immuni.2014.02.013. Epub 2014 Apr 10. PMID: 24726877

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biofilm formation in bacteria

Pseudomonas aeruginosa and biofilms: new insights on antibiotic tolerance

Dr. Dao Nguyen investigated the behavior of Pseudomonas aeruginosa, a common bacteria in patients with Cystic Fibrosis. Her research identified that when bacteria are starved, they develop a starvation-signaling stringent response, which allows them to better adapt and survive. This research showed that inactivating this protective mechanism can sensitize biofilms to various antibiotics, thus providing new insights on the mechanisms of antibiotic tolerance.

View the full publication here: Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Nguyen D, Joshi-Datar A, Lepine F, Bauerle E, Olakanmi O, Beer K, McKay G, Siehnel R, Schafhauser J, Wang Y, Britigan BE, Singh PK. Science. 2011 Nov 18;334(6058):982-6. doi: 10.1126/science.1211037. PMID: 22096200

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