Category Archives: Research Themes

Pulmonary Research Themes

According to the WHO, respiratory disorders are leading causes of death world-wide (second only to heart attack & stroke). These include diseases such as obstructive lung diseases and pulmonary infections. As a result, our research is focused around four main pulmonary research themes. These include: chronic airways disease, lung injury and infection, neuromuscular dysfunction in respiratory diseases, and sleep-disordered breathing.

Above all, a multidisciplinary approach is used to study the basic mechanisms of a number of diseases. These include asthma, chronic obstructive pulmonary disease, pulmonary infections, cystic fibrosis, sleep apnea, respiratory muscle disorders, pulmonary fibrosis, lung injury, and rare respiratory diseases. Research at the Meakins also involves the study of human physiology and tissues in parallel with relevant animal and cell culture models. Furthermore, research is facilitated by the availability of a variety of core facilities for both clinical and fundamental studies.

Learn more about our research themes here.

Below you will see posts and news items related to our research themes.

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.

Respiratory Research Canada: Meakins-Christie Laboratories of the RI-MUHC

2019 Respiratory Research News Meakins-Christie Laboratories

  • Congratulations to Dr. Simon Rousseau and Dr. Amin Emad on receiving seed funding from the McGill initiative in Computational Medicine ResearchMatch competition. The ResearchMatch program of the McGill initiative in Computational Medicine (MiCM) was developed in an effort to better connect life science and clinical researchers with colleagues focused on data sciences. Their project will examine Artificial Intelligence-informed molecular profiling of the frequency of pulmonary exacerbations in Cystic Fibrosis. Read more here. (July 2019)
  • 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: Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa. Published in: Proceedings of the National Academy of Sciences. (July 2019)
  • The 30th annual Respiratory Research Day featured 54 oral and poster presentations. Thanks to all our participants for attending and presenting your research. The winners for best oral presentation were: Lauren Tracey (MSc Student with Dr. Dennis Jensen) and Megan Hammell (MSc Student with Dr. Anne-Marie Lauzon). The winners for best poster presentation were: Jonathon Campbell (Clinical Fellow with Dr. Kevin Schwartzman), Kim Tran (MSc Student with Dr. Maziar Divangahi), Lisa Hennemann (MSc Student with Dr. Dao Nguyen), Erwan Pernet (PDF with Dr. Maziar Divangahi) and Vanessa Moarbes (PhD Student with Dr. Elizabeth Fixman). Congratulations to all our winners! (June 2019)
  • Lisa Hennemann (MSc Student with Dr. Dao Nguyen) won an award for best poster presentation at the annual MIMM Graduate Research Day. (May 2019)
Leukotriene B4–type I interferon axis regulates macrophage-mediated disease tolerance to influenza infection
  • Dr. Erwan Pernet (PDF with Dr. Maziar Divangahi) is lead author on a new study published in Nature Microbiology. Dr. Pernet and colleagues have identified a new role for the lipid mediator Leukotriene B4 in the lung. They show that the LTB4 molecule is capable of not only reducing collateral tissue damage caused by immune responses but also enhancing host survival. These novel findings have promising clinical implications in the near future for the treatment of flu. Read the press release here. Read the article here. (May 2019)
  • Congratulations to Dr. Julien Malet (PDF with Dr. Dao Nguyen) on receiving a FRQS Postdoctoral Fellowship award for his project entitled “Etude du cycle intracellulaire de Pseudomonas aeruginosa et de son rôle dans la fibrose kystique”. (May 2019)
  • Congratulations to Dr. Eva Kaufmann (PDF with Dr. Maziar Divangahi) on receiving a FRQS Postdoctoral Fellowship award for her project entitled “Reprogrammation des cellules souches par le BCG: une nouvelle approche pour le dévelopmment d’un vaccin contre la tuberculose.” (May 2019)
  • Congratulations to Dr. Nargis Khan (PDF with Dr. Maziar Divangahi) on receiving a CIHR Fellowship for her project entitled “An IFN-iron axis reprograms hematopoietic stem cells to generate trained immunity” as well as a FRQS Postdoctoral Fellowship award for her project entitled “Impact du microbiote intestinal dans la defense de l’hôte contre la tuberculose”. (May 2019)
  • Congratulations to Ms. Amanda Bianco (MEng with Dr. Anne-Marie Lauzon) on receiving a FRQNT Masters Award for her project entitled “Contrôle des tissus au comportement non-linéaire et viscoélastique pour le développement d’appareil biomédical”. (May 2019)
  • Congratulations to the following FRQS 2019-2020 Chercheurs Boursiers and Chercheurs-Boursiers Cliniciens Awardees: Dr. Deborah Assayag (Junior 1), Dr. Maziar Divangahi (Senior), Dr. Nicole Ezer (Junior 1), and Dr. Benjamin Smith (Junior 2). (May 2019)
  • Congratulations to Megan Hammell (first year MSc student with Dr. Anne-Marie Lauzon) who won FIRST PLACE for her oral presentation during the 5th Biological and Biomedical Engineering Symposium at McGill University. (May 2019)
  • Dr. James Martin and Dr. Shawn Aaron received a Research Leadership Award from CTS at the CRC 2019 in recognition of their leadership, service and contributions to the field of respiratory medicine and research. Read more here. (April 2019)
  • Dr. Sabah Hussain has been appointed a Distinguished James McGill Professor in recognition of his exceptional work and outstanding achievements. This Professorship is McGill University’s way of recognizing respected scholars and their valued contributions. (May 2019).
  • Dr. Dick Menzies, Director of the Respiratory Epidemiology Unit at McGill and McGill’s World Health Organization Collaborating Centre in TB Research, has been named recipient of the 2019 CIHR-ICRH/CTS Distinguished Lecturer Award in Respiratory Sciences. Read more here. (April 2019).
  • Dr. Sabah Hussain is part of a new research team funded by CIHR. The team is led by Dr. José Morais (MeDIC program) and will investigate the metabolic and molecular mechanisms underpinning inactivity-induced muscle loss and the underlying protective effects of an exercise countermeasure. Read more here. (April 2019)
  • New publication in Mucosal Immunology by Drs. Irah King, Maziar Divangahi, and Dick Menzies showed that anti-tuberculosis drugs caused changes to gut microbiota – the diverse community of microbes living our intestines – and increased susceptibility to Mycobacterium tuberculosis infection. Read more here. (March 2019)
  • Congratulations to the following CIHR Project Grant Recipients from the Fall 2018 Competition! Dr. Carolyn Baglole: Immunological consequences of inhaled cannabis and selected cannabinoids. Dr. Elizabeth Fixman: STAT6-dependent control of innate immunity as a target for therapeutic intervention in asthma. Dr. Sabah Hussain: Regulation of skeletal muscle function by PINK-1-Parkin mitophagy pathway. Dr. Arnold Kristof: Impact of Protein Nutrition in Critically-ill Patients. Dr. Benjamin Smith: A genome-wide association study of dysanapsis. Dr. Andrea Benedetti: Diagnostic Accuracy of the Patient Health Questionnaire-9 for Detecting Major Depression: An Updated Systematic Review and Independent Participant Data Meta-analysis. (January 2019)
  • Read how Meakins and RESP members, together with the McGill International TB Centre are moving towards the WHO’s goal of eliminating TB by 2030. Confronting a Killer – Med e-News. (January 2019)
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:

gut microbiome research

Anti-TB drugs can increase risk of TB re-infection

A study published in Mucosal Immunology by Drs. Irah King and Maziar Divangahi showed that anti-TB drugs ( anti-tuberculosis drugs) caused changes to gut microbiota, thereby compromising immunity. This then led to an increased susceptibility to Mycobacterium tuberculosis infection.

Current treatments for tuberculosis (TB) are very effective in controlling TB infection caused by Mycobacterium tuberculosis (Mtb). They don’t, however, always prevent reinfection. Why this happens is one of the long-standing questions in TB research.

Gut microbiota are critical to keeping us healthy; they help to digest food, combat pathogenic microbes and reinforce our immune system. Recent research has shown that chronic use of antibiotic leads to disruption of this community, which can in turn lead to dysregulation of the immune system.  It remains unclear, however, whether changes in the composition of the microbes living in our gut have an influence on TB infection. 

The research team treated mice with the most commonly used anti-TB drugs – isoniazid, rifampicin and pyrazinamide – for a period of eight weeks. They found that while all three drugs significantly altered the composition of the mice’s gut microbiome, only mice treated with isoniazid combined with pyrazinamide showed an increase in susceptibility to Mtb infection. Transplanting feces from healthy mice into animals treated with anti-TB drugs was sufficient to restore immunity to Mtb. The team also evaluated a number of lung cell types known to be important for resistance to Mtb infection. Following anti-TB treatment, alveolar macrophages, a type of immune cell located in the airways of mice and humans and the first cell to encounter Mtb upon infection, were compromised in their ability to kill Mtb.

“Anti-TB therapies have been incredibly efficient in controlling the TB epidemic by decreasing morbidity and mortality associated with Mtb. Now, this work provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection.’’

– Irah King

Read the full press release here:

View the full publication:

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis. Khan N, Mendonca L, Dhariwal A, Fontes G, Menzies D, Xia J, Divangahi M, King IL. Mucosal Immunol. 2019 May;12(3):772-783. doi: 10.1038/s41385-019-0147-3. Epub 2019 Feb 19. PMID: 30783183

View articles and interviews about this research:

Divangahi and Nargis Khan Science immunology Tuberculosis publication

Beyond Killing Tuberculosis

Dr. Maziar Divangahi’s May 2018 publication in Science Immunology tries to explain why the vast majority of people infected with Mycobacterium tuberculosis (Mtb) can tolerate the infection without developing disease. 

Dr. Divangahi’s team found that rather than fighting to resist the pathogen, the body’s tolerance to Mtb is the key mechanism for preventing the spread of the infection. More surprisingly, they found that having excessive levels of T cells, which are known as soldiers of our immune system, could cause more harm than good. The study determined that the mitochondrial protein cyclophilin D (CypD) acts as a key checkpoint for T cell metabolism and regulates disease tolerance in TB. (May 2018)

View articles and interviews about this research:

Flu vaccine and immunotherapies

Dr. Maziar Divangahi was interviewed by CBC Homerun 88.5 FM about his latest research on the flu vaccine. His lab has taken on the challenge of trying to understand how the mechanisms of the immune system fight the flu in the hopes of finding new immunotherapies to combat the virus.

The discovery of the RIPK3 protein that is involved in the regulation of immune response to the flu means help may be on the horizon. Their findings were published in the open-access journal PLoS Pathogens in 2017. (February 2018)

Full publication: RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection. Downey J, Pernet E, Coulombe F, Allard B, Meunier I, Jaworska J, Qureshi S, Vinh DC, Martin JG, Joubert P, Divangahi M. PLoS Pathog. 2017 Apr 14;13(4):e1006326. doi: 10.1371/journal.ppat.1006326. eCollection 2017 Apr. PMID: 28410401

View articles and interviews about this research:

Human Airway Branch Variation and Chronic Obstructive Pulmonary Disease

Airway Branching Associated with COPD Risk

Dr. Benjamin Smith, in collaboration with Dr. Carolyn Baglole and Columbia University Irving Medical Center, published “Human Airway Branch Variation and Chronic Obstructive Pulmonary Disease” in the Proceedings of the National Academy of Sciences. Together, their study shows that the internal anatomy of our lungs is surprisingly variable. Furthermore, some of those variations are associated with a greater risk of chronic obstructive pulmonary disease (COPD). (January 2018)

View full publication: Human airway branch variation and chronic obstructive pulmonary disease. Smith BM, Traboulsi H, Austin JHM, Manichaikul A, Hoffman EA, Bleecker ER, Cardoso WV, Cooper C, Couper DJ, Dashnaw SM, Guo J, Han MK, Hansel NN, Hughes EW, Jacobs DR Jr, Kanner RE, Kaufman JD, Kleerup E, Lin CL, Liu K, Lo Cascio CM, Martinez FJ, Nguyen JN, Prince MR, Rennard S, Rich SS, Simon L, Sun Y, Watson KE, Woodruff PG, Baglole CJ, Barr RG; MESA Lung and SPIROMICS investigators. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E974-E981. doi: 10.1073/pnas.1715564115. Epub 2018 Jan 16. PMID: 29339516

View articles and interviews about this research:

Cell 2018: BCG Educates hematopoietic stem cells to generate protective innate immunity against TB. M Divangahi

BCG-iv Induces Innate Immune Protection Against M. tuberculosis

Dr. Maziar Divangahi, his lab, and collaborators at McGill University and University of Montreal published a paper in Cell. Their work shows BCG-iv induces trained immunity through education of hematopoietic stem cells and offers long-term innate immune protection against M. tuberculosis infection. 

Up until now, efforts in generating a vaccine against TB have been mainly focused on T cells, with very disappointing outcomes in both pre-clinical as well as clinical trials. Now, Dr. Divangahi’s and Barreiro’s teams have shown for the first time that when BCG is administered to mice in a way that enables access to the bone marrow, it can reprogram stem cells. Dr. Eva Kaufmann, a postdoctoral fellow working on the project, was also interviewed by Radio-Canada. (January 2018) 

About the study

BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis by Eva Kaufmann, Joaquin Sanz, Jonathan L. Dunn, Nargis Khan, Laura E. Mendonça, Alain Pacis, Fanny Tzelepis, Erwan Pernet, Anne Dumaine, Jean-Christophe Grenier, Florence Mailhot-Léonard, Eisha Ahmed, Jad Belle, Rickvinder Besla, Bruce Mazer, Irah L. King, Anastasia Nijnik, Clinton S. Robbins, Luis B. Barreiro, and Maziar Divangahi, was published Jan. 11, 2018, in Cell. DOI: 10.1016/j.cell.2017.12.031

This study was funded by the Canadian Institutes of Health Research.

View articles and interviews about this research: