Category Archives: Faculty

View recent posts and news from our faculty members. For our faculty profiles, read more here: https://www.meakinsmcgill.com/faculty-members/ 

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

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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

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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)

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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

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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

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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.

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Pulmonary research in Canada: the Meakins-Christie Laboratories

Dr. Basil Petrof appointed Director of the Meakins-Christie Laboratories

Dr. Basil Petrof, Professor of Medicine, has been appointed Director of the Meakins-Christie Laboratories effective May 15, 2017, for a five-year term. As Director, Dr. Petrof will be responsible for the scientific leadership and administration of the Meakins-Christie Laboratories. Dr. Petrof is an accomplished and internationally recognized scientist for his work on respiratory muscle dysfunction and sleep-disordered breathing.

funding news for the Meakins-Christie Laboratories

Prognostic and therapeutic utility of human antigen R (HUR) in idiopathic pulmonary fibrosis

Dr. Carolyn Baglole was interviewed about her recent grant entitled “Prognostic and therapeutic utility of human antigen R (HUR) in idiopathic pulmonary fibrosis”. Her project received 2 year funding from Boehringer-Ingleheim’s Innovation in Understanding ILD (BUILD) program. (April 2017)

Read more here: BUILD grant breathes life into lung disease research. Supported by funding from Boehringer Ingelheim (Canada) Ltd, Carolyn Baglole hopes to unravel the mystery of idiopathic pulmonary fibrosis, a fatal lung disease that affects some 15,000 Canadians.

Pulmonary research group in Canada: the Meakins-Christie Laboratories

STAT6-IP reduces the development of allergic-type lung inflammation and airway hyperresponsiveness

Dr. Elizabeth Fixman and Dr. Brian Ward (IDIGH Program at RI-MUHC) co-authored a study in the Journal of Leukocyte Biology demonstrating that STAT6-IP reduces the development of allergic-type lung inflammation and airway hyperresponsiveness in mice re-challenged with respiratory syncytial virus (RSV). (February 2017)

Read the full press release here

Scientists discover peptide that could reduce the incidence of RSV-related asthma

New research published in the Journal of Leukocyte Biology suggests that a peptide developed to inhibit a key regulator of asthma responses reduces development of inflammation and ‘twitchy’ airways in mice

For Details: Bharat T. Srinivasa, Katherine H. Restori, Jichuan Shan, Louis Cyr, Li Xing, Soojin Lee, Brian J. Ward, and Elizabeth D. Fixman. STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection. doi:10.1189/jlb.4A0215-062RR ; http://www.jleukbio.org/content/101/2/519.abstract

RI-MUHC researchers lead the first oral desensitization program in Canada

Desensitization program helps kids with milk allergies

New milk allergy research being led at the RI-MUHC. Pediatric allergy and immunology specialists Dr. Bruce Mazer and Dr. Moshe Ben-Shoshan (Montreal Children’s Hospital) started the GET-FACTS (Genetics, Environment and Therapies: Food Allergy Clinical Tolerance Studies) study in 2012.

The program is having good success with helping children with milk allergies build up tolerance to milk protein by introducing the allergen very slowly into the diet. They were interviewed by CTV, La Presse, Radio-Canada, 98,5 fm, the Gazette, CJAD and Le Devoir (September 2016).

More about the study at GET-FACTS: https://www.getfactsmilk.com/ https://www.getfactsmilk.com/

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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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