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.

A colorimetric nanosurface fluidic platform for rapid phenotypic antibiotic susceptibility testing. Dao Nguyen received MI4 seed funding

Rapid phenotypic antibiotic susceptibility testing

Dr. Dao Nguyen and Dr. Sara Mahshid receive MI4 Seed Funding to develop an ultrasensitive colorimetric fluidic assay for rapid phenotypic antibiotic susceptibility testing. Antibiotic resistant bacteria are responsible for 700,000 deaths annually, a figure that is projected to rise to 10 million deaths per year by 2050 if no action is taken to halt this global threat. The overuse of antibiotics and the prescription of antibiotics to which bacteria are not susceptible, contribute to the rise of antibiotic resistance. This proposal will develop an ultrasensitive colorimetric fluidic assay for rapid phenotypic antibiotic susceptibility testing (AST). The project is anticipated to reduce the turnaround time of the AST to less than 1 hour compared to 3-4 days using conventional AST methods.

Read more about the project:

MI4 Seed Fund Grants – Round 3: A colorimetric nanosurface fluidic platform for rapid phenotypic antibiotic susceptibility testing (Dr. Dao Nguyen and Dr. Sara Mahshid)

March 24 is World TB Day, 2021 Over the next 10 years, Dr. Dick Menzies and the McGill International TB Centre will receive $17.2 million from the CIHR-III for TB Research.

World TB Day 2021

World TB Day 2021 was March 24. Dick Menzies is one of the researchers highlighted by the CIHR’s Institute of Infection and Immunity (CIHR-III), for his work in the field of tuberculosis (TB).

Over the past years the CIHR has provided substantial funding to Dr. Menzies and his research team at the TB Centre. Putting the funds to good use, Dr. Menzies has defined a treatment protocol for TB, which is now in use across North America. Now it is time to take that research further.

In response to a joint application made by CAB-V (Canada, Australia, Benin and Vietnam), an international network led by Dr. Menzies, the CIHR-III has awarded the McGill International TB Centre a further $17.2 million over the next ten years to continue its research and clinical trials on the treatment, diagnosis and prevention of TB. Further studies are being planned for the near future at sites and with co-investigators across Canada and around the world.

About Dr. Menzies:

Dr. Menzies is the Director of the McGill International TB Centre, Canada Research Chair in TB Research, member of the RI-MUHC RESP Program and Associate Member of the Meakins-Christie Laboratories.

Read more about Dr. Menzies and TB Research here:

It is time to improve treatment options for rare lung diseases such as progressive fibrosing interstitial lung disease.

Improving Outcomes for ILD Patients

As a specialist in Interstitial Lung Disease (ILD) at the Meakins-Christie Laboratories, Ilan Azuelos, MD is an ardent promoter of improving outcomes for ILD patients. Treatment options for people with rare lung diseases, such as progressive fibrosing interstitial pulmonary fibrosis, may portend a life expectancy of between five and six and a half years after onset of symptoms. Dr. Azuelos knows that with research and education of the general public, this life expectancy can be improved.

“Ainsi, les personnes affligées de cette maladie seraient en mesure de passer plus de temps avec leur famille et de profiter au maximum de la vie.”

Ilan Azuelos, MD, MSc

Fortunately, programs have been initiated to address this area of medicine. MEDTEQ+, a pan-Canadian consortium for medical innovation, is bringing together industry leaders such as Boehringer Ingelheim Canada in partnership against PF-ILD. They aim to identify potential solutions to address the gaps in care for patients with IPD-PF, with the goal of accelerating access to treatments that delay the deterioration of lung function.

With the general public more aware of the symptoms of the onset of lung disease, patients could seek out treatment at an earlier stage. Increased funding for research would lead to a better understanding and the development of novel treatment options. Each would play an important role in a better, perhaps longer, life after diagnosis.

Read the following articles to learn more of the importance of improving education and treatment options for patients with ILD:

Nicole Ezer and the CONTAIN COVID-19 trial at the RI-MUHC with ciclesonide

COVID-19 contained with a nasal spray

Dr. Nicole Ezer is helping lead a trial with ciclesonide that promises to reduce symptoms of COVID-19. Read our initial posts about the trial here: Ciclesonide Clinical Trial for COVID-19 and ‘Contain COVID-19’ – in its earliest phases.

The Journal de Montreal reports the pursuits of our Quebec researchers and physicians in leading this trial. Ciclesonide has both anti-viral and anti-inflammatory properties. Of the few trials testing ciclesonide, the one led here at the MUHC is the only one that is studying the administration of the drug by nasal spray and inhaler. Inhalers and sprays have the advantage of acting directly in the nose, the airways, and the lungs, right were the SARS-CoV-2 virus is actually replicating. The goal of the trial is to determine whether ciclesonide reduces respiratory symptoms and in turn reduces hospitalizations.

Dr. Ezer is an Assistant Professor in the Department of Medicine at McGill University and a Junior Scientist with the RI-MUHC RESP Program.

To learn more about the trial or participate and the entire research team: www.contain-covid19.com/contenez-la-covid-19/  

Read the article:

COVID-19: un vaporisateur nasal en renfort. par Stéphanie Martin, Journal de Montréal. December 31, 2020.

Larry Lands and Laurent Pharmaceuticles to begin a clinical trial on COVID-19 treatment with LAU-7b, a pro-resolving drug with potential antiviral properties against coronavirus

LAU-7b clinical trial on COVID-19 treatment

The RI-MUHC is currently enrolling patients in RESOLUTION, a clinical trial of LAU-7b for the treatment of hospitalized COVID-19 patients. The drug acts on lung inflammation and showed potent antiviral effects in-vitro against SARS-CoV-2. Results from previous studies in adult CF patients showed an important reduction of key pro-inflammatory biomarkers at the onset of a pulmonary exacerbation episodes, suggestive of a protective effect of the drug on the lungs.

Read more here:

Phase 2 clinical study with LAU-7b

An original post from April 2020 described the start of the clinical trial:

Laurent Pharmaceuticals, a McGill spinoff, will run a Phase 2 clinical study with LAU-7b, a pro-resolving drug with potential antiviral properties against coronavirus.

Larry Lands is the Chief Medical Advisor for Laurent Pharmaceuticals. Laurent Pharmaceuticals Inc. is planning to test its lead drug LAU-7b in patients with COVID-19 disease. LAU-7b was recently identified as a potential anti-viral therapeutic option for COVID-19 during a drug-library screening effort.

The Research Institute of the MUHC is presently enrolling participants in the study, called RESOLUTION. LAU-7b is a novel oral form of a drug called fenretinide, which inhibits the inflammatory reaction of the body to the virus. This study could lead to improved treatments for hospitalized COVID-19 patients who are at higher risk of developing complications.

“Thanks to its inflammation-controlling properties, low-dose fenretinide triggers a natural mechanism – the body’s own resolution of the inflammation process – which keeps the inflammatory response under control without suppressing its protective immune role.”

Dr. Larry Lands

Read more here:

McGill spinoff Laurent Pharmaceuticals to begin clinical trial on COVID-19 treatment. Company to run a Phase 2 clinical study with LAU-7b, a pro-resolving drug with potential antiviral properties against coronavirus. By Junji Nishihata. McGill Reporter. April 11, 2020.

Dr. Dao Nguyen dreams of creating the Antimicrobial Resistance Centre to research a world without effective antibiotics

Preventing a post-antibiotic world

It is World Antimicrobial Awareness Week and Dr. Dao Nguyen, a researcher at MI4 and clinician-scientist at the Meakins-Christie Laboratories and the RI-MUHC, dreams of applying her knowledge and skills to preventing a post-antibiotic world. We have all read about the increasing strength of bacteria and hear how our present-day antibiotics are becoming ineffective. In fact, it is estimated that 20-30% of currently existing bacteria are resistant to available drugs. The WHO estimates that by 2050 drug-resistant organisms will surpass cancer as the primary cause of death. This is the problem Dr. Nguyen would like to take on.

She would like to create an interdisciplinary Antimicrobial Resistance Centre where members of the scientific community can combine their knowledge and work towards preventing a post-antibiotic world. Thanks to the MUHC Foundation’s fundraising efforts, Dr. Nguyen’s dream of an Antimicrobial Resistance Centre will likely come to fruition – something we should each be thankful for. Dr. Nguyen explains:

“Let’s say you accidentally cut yourself. Right now, you can get treatment from a topical cream or take antibiotic pills to cure the infection in a few days,” says Dr. Nguyen. “With antibiotic-resistant bacteria, it wouldn’t be treated as easily and the infection could spread requiring an amputation.”

An amputation would be an extreme result from a simple cut on the finger, yet an all too possible outcome if research is not carried out and solutions are not found.

Read the interview with Dr. Dao Nguyen here:

Dr. Bruce Mazer, Associate Scientific Director of the COVID-19 Immunity Taskforce, on understanding COVID-19 immunity.

Decoding Immunity to COVID-19

This week on Health Matters, Centre universitaire de santé McGill – McGill University Health Centre physician and researcher, Dr. Bruce Mazer discusses findings and unanswered questions about decoding immunity to COVID-19 and his role in the COVID-19 Immunity Task Force.

Dr. Mazer, Associate Scientific Director of the Taskforce, sums up the goal of their work as: to understand the prevalence of the virus in the community at large, and to learn about how the body responds to the virus. Completed studies in this area have revealed the following:

“We know that the prevalence of the antibodies in the population of healthy blood donors is between 0.7% and 1.0% of the population, as high as 2.9% in certain areas of Quebec and Ontario.”

Dr. Bruce Mazer

Although these numbers indicate a lack of herd immunity, he feels it is more important to understand how to treat individuals who are most at risk, to develop a vaccine, and to find answers to some of their yet-to-be-answered questions. Finding answers to questions such as why some people are more affected by this virus than others, why some people are more affected by previous viruses but not this one, and how long the antibodies created by vaccination will last in the body, would go a long way in decoding immunity to COVID-19.

Listen to Dr. Mazer’s interview by Julie Quenneville on:

Dr. Nicole Ezer of the RI-MUHC's RESP Program on what doctors have learned about treating patients with COVID-19.

Treatments for COVID-19

Since the spring physicians have been discovering optimal treatments for COVID-19 symptoms. Dr. Nicole Ezer, a researcher with the RI-MUHC’s RESP Program, was interviewed on this subject on CJAD. Dr. Ezer explained:

Initially it was very challenging to know how to treat patients appropriately, in particular patients who presented in the emergency room and required lots of oxygen.

Dr. Nicole Ezer

Since the spring the medical community has learned a lot about this virus, thanks in part to the many publications that have come out.

The names of medications which have been found best to help hospitalized patients include the steroid dexamethasone and the antiviral remdesivir. These two medications have been very helpful in not only reducing the amount of time patients spend in hospital, but also the number of deaths caused by this virus. These were important discoveries for the medical community.

The focus remains on finding treatments to help patients with less severe symptoms. To this end, all residents of Quebec experiencing milder COVID-19 symptoms are encouraged to take part in an ongoing study at the MUHC called contain-covid19.com. No in-person visits are required. After acceptance into the trial participants will receive their medication by mail. All communications are done remotely. This is one way we can all be involved in the hunt for treatments for COVID-19.

Listen to Dr. Ezer’s interview

What have doctors learned about treating COVID-19 patients? on the Aaron Rand Show, CJAD.

Dr. Dao Nguyen discusses the importance of the work undertaken by MI4 researchers in an interview in Health Matters..

The M[i]4 Initiative

Dr. Dao Nguyen is a researcher with the Meakins-Christie Labs and M[i]4 (the McGill Interdisciplinary Initiative in Infection and Immunity). In this interview, which appears on the MUHC Foundation’s Health Matters Series, Dr. Nguyen explains the value of the M[i]4 initiative. Not only does this initiative provide researchers with funding for their research, it also enables them to share ideas across numerous disciplines, thus increasing their chances of developing new ideas and finding solutions.

Dr. Nguyen believes that when the general public hears the word ‘infection’, their mind is likely to focus on COVID-19; however infection, antibiotics and immunity go far beyond this virus. Infection control is important for individuals in many circumstances, such as undergoing surgery, chemotherapy or even when someone cuts their hand. Over time, infections are getting stronger and new antibiotics are needed to treat them. Pharmaceutical companies were committed to the development of new treatments in the 60’s, 70’s and 80’s, but are now focusing their efforts in more profitable areas. This leaves a void which the M[i]4 initiative hopes to fill.

Although M[i]4 receives funding from various sources, donations also play an important role. A donation can help to move an idea from paper to the laboratory. Donations can help with the completion of a project or infrastructure. Dr. Nguyen highly values donations received, and appreciates this financial support for their valuable work.

Listen to La recherche essentielle du CUSM pour combattre le COVID-19 on Health Matters.

To listen to the interview:

MUHC Health Matters News Series
Web: https://bit.ly/3beMKBH
Spotify: https://spoti.fi/32HFxrc
Apple: https://apple.co/35NvItS

Maziar Divangahi, Principal Investigator, Nargis Khan, Postdoctoral Fellow and first author of the study, Jeff Downey, PhD candidate and co-first author of the study

Cracking the Code of Stem Cells in TB

Congratulations Dr Nargis Khan (PDF) and Jeffrey Downey (PhD trainee), from the Dr. Maziar Divangahi laboratory, on their new study published today in Cell! The study shows that stem cells can be targeted for protective vaccination as well as be hijacked by a pathogen to increase TB virulence.

Dr. Maziar Divangahi’s latest study is in follow up to his previous work that showed that exposure of bone marrow stem cells to a live BCG vaccine (the only available vaccine for TB) reprograms these cells to generate protective innate immunity against TB. However, it was still not know what happened to these stem cells after they were exposed to the pathogen Mycobacterium tuberculosis (Mtb). In this study, the team demonstrates that soon after Mtb infection, the bacteria translocate from the lungs to the bone marrow and reprograms stem cells to impair innate immunity against TB.


“What’s new in this study is that we now know that Mtb hijacks the immune response at the very early phase of infection by accessing the bone marrow and manipulating stem cells. This leads to the generation of impaired innate immune cells, which are effectively incapacitated to fight the infection in the lung, thus allowing the bacteria to grow.”

Dr. Nargis Khan

Once the function of the stem cells has been corrupted by the Mtb pathogen, they lose their ability to fight off the infection in the lungs. In essence, alternative approaches that crack the protective code of stem cells in the bone marrow are urgently needed to eradicate TB.

Read the News Releases:

Read the publication:

Nargis Khan, Jeffrey Downey, Joaquin Sanz, Eva Kaufmann, Birte Blankenhaus, Alain Pacis, Erwan Pernet, Eisha Ahmed, Silvia Cardoso, Anastasia Nijnik, Bruce Mazer, Christopher Sassetti, Marcel A. Behr, Miguel P. Soares, Luis B. Barreiro and Maziar Divangahi. M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity. Cell. 2020. 183(3): p752-770.E22.