The Centre for Respiratory Research at McGill University and the Research Institute of the McGill University Health Centre
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.
DR. MARGARET BECKLAKE: A PIONEERING LEADER IN RESPIRATORY MEDICINE
The Montreal Chest Institute Foundation is proud to honour Dr. Becklake’s legacy and immense contribution in developing generations of respiratory clinicians and researchers by launching the Dr. Margaret Becklake Fellowship. This fellowship will be awarded to at least one trainee in respiratory research every year and will pay her or his salary as s/he conducts research under the supervision of scientists at the Montreal Chest Institute of the McGill University Health Centre.
Recipients will be chosen from low- and middle-income countries as well as from Canadian Indigenous communities. Over the course of her career, Dr. Becklake had a major interest in respiratory health in lower-income countries, including in childhood asthma and occupational lung disease. She conducted research in this area for many years. Dr. Becklake also trained and hosted students in respiratory research from lower-income countries, who then became leaders in research and care in those countries.
Help us train the next generation of researchers and specialists in areas of the world where the need is greatest. Help us share the expertise we have at the Montreal Chest Institute around the globe. Help us continue Dr. Becklake’s legacy.
Dr. Margaret Becklake immigrated to Montreal in 1957 from South Africa. Her impact on respiratory care, research and teaching was profound. With other members of the McGill faculty, she worked on occupational lung disease, an interest she maintained from her early medical career in South Africa. She established the now well-known Respiratory Epidemiology and Clinical Research Unit at McGill and at the Montreal Chest Institute.
Dr. Becklake was renowned for her insistence upon the importance of a clearly stated, relevant research question and more generally for her clarity and insight. She was also unfailingly devoted to her patients and their families. The research unit she founded flourishes today, as it continues to emphasize respiratory research of direct relevance to patients and communities.
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.
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.
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.”
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.
November 14 is World Diabetes Day! In the lead-up to this, we are promoting work by Dr. Sushmita Pamidi, RESP program scientist, and Raphieal Newbold (MSc graduate). They are studying the link that may lead to better health for mother and baby. Sleep apnea has strong links with type 2 diabetes and is quite prevalent in pregnancy. The research team found that increasing severity of sleep apnea in pregnant women with gestational diabetes was, in fact, linked with higher glucose levels at night. It is possible that improved glucose control in pregnancy by treatment of sleep apnea could lead to improved overall outcomes for mother and baby.
A study published by the group in CHEST reveals that untreated sleep apnea can affect nighttime glucose levels of pregnant women who have gestational diabetes. Dr. Sushmita Pamidiand her team of researchers who carried out the study discovered a clear relationship between sleep, pregnancy, and type 2 diabetes.
The results of this study shed light on the importance of recognizing and treating sleep apnea in these pregnant women, an area that has not previously received much attention. Type 2 diabetes in pregnant women increases their risk for complications during pregnancy, after childbirth, and often results in an increased prevalence of type 2 diabetes in the children during their lifetime.
In present day, intervention with pregnant women experiencing gestational diabetes primarily focuses on improved nutrition and increased exercise. This study has brought to light another important focus for medical attention as summarized by Dr. Pamidi:
“Overall, we need to think more about the importance of sleep disorders in pregnant women. This may be a missing link in the lifestyle recommendations for this population.”
Dr. Sushmita Pamidi
Read the RI-MUHC story for Diabetes Awareness Month & World Diabetes Day:
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:
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.
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. Nguyenexplains 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.
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.
This award is given to a researcher from the Montreal Children’s Hospital community whose initiatives have made a unique and significant contribution to pediatric care.
Dr. McCusker is passionate about her work, which surely explains her success. Over the past few years, she and her team have cured children of allergies to tree nuts, milk and eggs thanks to a desensitization program she helped put in place. She has led her team to positive clinical research outcomes, advancing treatments and helping empower children with allergies.
“I love my job! I also get to play with kids and help reduce parents’ anxiety.”
Dr. Christine McCusker
Learn more about Dr. McCusker and the Montreal Children’s Hospital Foundation Pfizer Research Award of Excellence: