Timeline of Research Achievements & Featured Articles
BCG Vaccine Offers Cross-protection Against Influenza
January 22, 2024
Publication in Nature Immunology by Maziar Divangahi and his research team describes how Bacille Calmette-Guérin (BCG) vaccination provides additional protection against unrelated pathogens, including influenza A viral infection. Nature Immunology 2024; 25(3):418-431.
All Airway Trees are Not Created Equal
July 26, 2023
A study by Benjamin Smith reveals that airway-to-lung size ratio is possibly the most important factor in death by lung disease. The results of this study showed that, overall, individuals with larger lungs had a higher resistance to COPD or other lung diseases. European Respiratory Journal. 2023; 61(6):2300551.
50 Years of Excellence in Respiratory Research
May 17, 2023
The Meakins-Christie Laboratories celebrate their 50th anniversary with a 2 day scientific symposium. A reception at the Maude Abbott Medical Museum opened the event. The guest list included Dr. Jonathan L. Meakins, grandson of Dr. Jonathan C. Meakins, the eminent respiratory researcher who, with his colleague Dr. Ronald Christie, lent his name to the Meakins-Christie Laboratories in 1972.
Vaping Can Cause Significant Harm to the Lungs
February 2, 2023
New research carried out in the lab of Carolyn Baglole, PhD, affirms that vaping can cause significant damage to the lungs. Even at this low level of exposure, the lung undergoes significant cellular and molecular changes. Vaping is therefore not a harmless tool to aid in smoking cessation. FASEB J. 2023 Feb;37(2):e22732.
Prenatal Programming of Alveolar Macrophages by Neutrophils Needed for Lung Health
January 5, 2023
Divangahi lab shows that the production of eicosanoids by neutrophils is required for reprogramming alveolar macrophages during early life in the developing lung. Furthermore, they demonstrate that in the absence of alveolar macrophage reprogramming by neutrophils, there is an increased susceptibility to LPS-induced acute lung injury, pulmonary influenza A virus and SARS-CoV-2 infections in preclinical models. Nature. 2023; 614(7948):530-538.
June 10, 2022
Study by Benjamin Smith suggests that dysanapsis of the lower airway and its association with airflow obstruction is specific to the lower airway and does not extend to the upper airway. Am J Respir Crit Care Med. 2022; 206(7):913-917.
Mtb Can Reprogram Stem Cells to Impair Innate Immunity Against TB
October 29, 2020
Publication in Cell by Maziar Divangahi shows that stem cells can be targeted for protective vaccination as well as be hijacked by a pathogen to increase TB virulence. Soon after Mtb infection, the bacteria translocate from the lungs to the bone marrow and reprograms stem cells to impair innate immunity against TB.
Chlorine Gas, Airway Inflammation and Cysteinyl Leukotrienes
August 28, 2020
Editorial: Chlorine Gas, Airway Inflammation, and Cysteinyl Leukotrienes: The Neutrophil Does Not Work Alone. Publication by James Martin shows that neutrophils, epithelial cells, and other lung cells all play a roll for Chlorine to induce airway hyperresponsiveness. Publication PMID: 32697598.
Dysanapsis Is a Strong Risk Factor for COPD
June 9, 2020
JAMA publication by Benjamin Smith highlights dysanapsis as a strong risk factor for chronic obstructive pulmonary disease (COPD). Dysanapsis is a developmental mismatch between airway and lung size. While the root cause for dysanapsis remains unknown, these findings help understand why COPD can occur in people who never smoked and do not have other risk factors.
β-glucan Induces Protective Trained Immunity
May 19, 2020
May 19, 2020. Cell Reports Publication by Maziar Divangahi shows that β-glucan induces protective trained immunity in human monocytes infected with Mycobacterium tuberculosis, as well as in mice infected with Mycobacterium tuberculosis. Their work is paving the way for both prophylactic and therapeutic use of β-glucan in TB.
Evolving Mechanisms of Disease Tolerance
December 20, 2019
Frontiers in Immunology editorial by Maziar Divangahi and Irah King discusses the history of disease tolerance. Reviews by Meakins members are prominently featured in this editorial.
New Role for the Lipid Mediator Leukotriene B4 in the Lung
August 4, 2019
Nature Microbiology publication by William Powell and Maziar Divangahi 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 in response to flu (influenza) infection, but also enhancing host survival.
Anti-TB Drugs Cause Changes to Gut Microbiota, Compromising Immunity
May 12, 2019
Mucosal Immunology publication by Irah King, Maziar Divangahi showed that anti-tuberculosis drugs caused changes to gut microbiota, thereby compromising immunity. This then led to an increased susceptibility to Mycobacterium tuberculosis infection. This work provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection.
New Cellular Target Can Weaken the Bacterium Pseudomonas aeruginosa
September 10, 2018
PNAS publication by Dao Nguyen identified a new cellular target that can weaken the bacterium Pseudomonas aeruginosa, a daunting microbe which can become highly tolerant to many antibiotics. They found that inhibition of the enzyme activity (superoxide dismutase) or the stress signaling system renders the pathogen more susceptible to antibiotics.
CypD is a Key Checkpoint for T Cell Metabolism and Regulates Disease Tolerance in TB
May 11, 2018
Science Immunology publication by Maziar Divangahi tries to explain why the vast majority of people infected with Mycobacterium tuberculosis (Mtb) can tolerate the infection without developing disease. The study determined that the mitochondrial protein cyclophilin D (CypD) acts as akey checkpointfor T cell metabolism and regulates disease tolerance in TB.
Variations in Lung Anatomy Associated with COPD
January 30, 2018
January 30, 2018. PNAS publication by Benjamin Smith and Carolyn Baglole shows that the internal anatomy of our lungs is surprisingly variable. Some of those variations are associated with a greater risk of chronic obstructive pulmonary disease (COPD).
BCG Educates Stem Cells for Protective Innate Immunity Against TB
January 11, 2018
Cell Publication: BCG Educates hematopoietic stem cells to generate protective innate immunity against TB. Publication by Maziar Divangahi shows 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 and offers long-term innate immune protection against M. tuberculosis infection.
Mechanical Ventilation Induces Diaphragmatic Dysfunction in Duchenne Muscular Dystrophy Mice
October 10, 2017
Editorial: Mechanical Ventilation for DMD: Sinner or Saint? Publication by Basil Petrof shows short‐term mechanical ventilation induces rapid diaphragmatic force loss and biochemical changes consistent with VIDD in mdx mice. This may have implications for the optimal use of intermittent mechanical ventilation in DMD patients. Original Publication PMID: 28786111.
RIPK3 Protein is Involved in the Regulation of Immune Response to the Flu
April 14, 2017
PLoS Pathogen publication by Maziar Divangahi, James Martin, Salman Qureshi. Their research is 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.
STAT6- Inhibitory Peptide May Reduce Incidence of RSV-Related Asthma
February 10, 2017
February 10, 2017. Journal of Leukocyte Biology publication by Elizabeth Fixman demonstrates that STAT6-IP reduces the development of allergic-type lung inflammation and airway hyperresponsiveness in mice re-challenged with respiratory syncytial virus. This peptide may reduce the incidence of RSV-related asthma.
First Primer on Tuberculosis in Nature Reviews Disease Primers
October 27, 2016
First Primer on Tuberculosis in Nature Reviews Disease Primers. Publication by Maziar Divangahi and colleagues.
Benefits of Newborn Screening for Cystic Fibrosis
May 15, 2016
Journal of Cystic Fibrosis publication by Larry Lands 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.
First Proof That Mechanical Ventilation Can Cause Human Diaphragm Dysfunction
April 14, 2016
Thorax Editorial: Respiratory muscle wasting in the ICU. Publication by Sabah Hussain provides the first proof that mechanical ventilation can cause contractile dysfunction of the diaphragm in humans. Original PMID: 27033022.
Toll-like Receptor Signalling in Regenerative Myogenesis: Friend and Foe
March 9, 2016
March 9, 2016. Journal of Pathology Commentary. Toll-like receptor signalling in regenerative myogenesis: friend and foe. Publication by Basil Petrof, Maziar Divangahi, Salman Qureshi suggests that macrophage function and skeletal muscle repair depends greatly upon the muscle injury context and the micro‐environment. Modifying the inflammatory milieu in dystrophic muscle may serve as a useful therapeutic measure in DMD. Original PMID: 26800321.
STAT6 Inhibitory Peptide Educated the Immune System From Developing an Allergic Response
February 29, 2016
Feb 29, 2016. Feature. 2015 Mucosal Immunology; 2011 Clinical & Experimental Allergy; 2007 Journal of Immunology. Publications by Elizabeth Fixman and Christine McCusker. Dr, Fixman developed STAT6-IP, a chimeric inhibitory peptide with the ability to enter cells and disrupt activity of the STAT6 transcription factor. STAT6 has been show to inhibit aberrant Th2 responses in the airways of preclinical models of asthma.
Variants of Pseudomonas aeruginosa Can Cause a Lot of Inflammation
July 31, 2015
July 31, 2015. Science Advances publication by Dao Nguyen shows that there are variants of Pseudomonas aeruginosa, a bacteria commonly found in Cystic Fibrosis patients, that can cause a lot of inflammation. Nguyen’s team is the first to make the connection between the bacteria and inflammation.
Nurturing Nanotubes: Role of Nanotubes Between T Cells and Airway Smooth Muscle
June 15, 2015
Journal of Immunology Top 10% In this Issue: Nurturing Nanotubes. Publication by James Martin elucidates the functional role of nanotubes between T cells and airway smooth muscle. Original PMID: 25934863.
T Cells and Airway Smooth Muscle Interactions in Asthma
July 14, 2014
July 14, 2014. Perspectives Editorial in the J of Physiology. In the field, it was still unknown whether airway smooth muscle activation by activated T cell binding could also affect airway smooth muscle contractility. Work by the Lauzon group provides evidence for this targeted T cell–airway smooth muscle cell interaction resulting in increased airway smooth muscle shortening velocity. The work shows that inflammatory cells promote airway smooth muscle hypercontractility in airway hyper-responsiveness and asthma. Original publication PMID: 24687581.
STAT-6 Inhibitory Peptide Inhibits Aberrant Th2 Responses in RSV Infection
June 5, 2014
European Journal of Immunology publication by Elizabeth Fixman. The STAT6 inhibitory peptide can educate the immune system away from developing an allergic response. STAT6 has been show to inhibit aberrant Th2 responses in the airways of preclinical models of respiratory syncytial virus infection.
Inhibition of PGE2 Increases Survival of Mice Infected With H1N1 Flu Virus
April 17, 2014
Immunity publication by William Powell, 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.
Starved Bacteria Can Better Adapt and Survive
November 18, 2011
Science Perspectives Feature: Antioxidant strategies to tolerate antibiotics. Publication by Dao Nguyen identified that when bacteria are starved, it allows them to better adapt and survive. Original Nguyen Publication PMID: 22096200.
Pseudomonas aeruginosa and Biofilms: New Insights on Antibiotic Tolerance
November 18, 2011
This Week in Science Feature: Arrest and Tolerate. Publication by Dao Nguyen on Pseudomonas aeruginosa and biofilms: new insights on antibiotic tolerance. Publication shows that antibiotic tolerance occurs, not because the targets of antibiotics have become inactive during growth arrest, but because starvation-sensing mechanisms generate protective responses. Original Publication PMID: 22096200.
Meakins-Christie Laboratories Founded
August 1, 1972
The Meakins-Christie Laboratories for Respiratory Research was officially opened in August 1972. From the beginning, the laboratories were designed to be interdisciplinary, and physiologists, physicians, epidemiologists, pathologists, radiologists, and biomedical engineers were invited to participate.
Pseudomonas aeruginosa and Biofilms: New Insights on Antibiotic Tolerance
This Week in Science Feature: Arrest and Tolerate. Publication by Dao Nguyen on Pseudomonas aeruginosa and biofilms: new insights on antibiotic tolerance. Publication shows that antibiotic tolerance occurs, not because the targets of antibiotics have become inactive during growth arrest, but because starvation-sensing mechanisms generate protective responses. Original Publication PMID: 22096200.
1972
Meakins-Christie Laboratories Founded
The Meakins-Christie Laboratories for Respiratory Research was officially opened in August 1972. From the beginning, the laboratories were designed to be interdisciplinary, and physiologists, physicians, epidemiologists, pathologists, radiologists, and biomedical engineers were invited to participate.