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Respiratory Research at the Meakins

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Timeline of Research Achievements & Featured Articles

Mtb Can Reprogram Stem Cells to Impair Innate Immunity Against TB

October 29, 2020

Mtb Can Reprogram Stem Cells to Impair Innate Immunity Against TB

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

Chlorine Gas, Airway Inflammation and Cysteinyl Leukotrienes

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

Dysanapsis Is a Strong Risk Factor for COPD

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

β-glucan Induces Protective Trained Immunity

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

Evolving Mechanisms of Disease Tolerance

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

New Role for the Lipid Mediator Leukotriene B4 in the Lung

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

Anti-TB Drugs Cause Changes to Gut Microbiota, Compromising Immunity

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

New Cellular Target Can Weaken the Bacterium Pseudomonas aeruginosa

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

CypD is a Key Checkpoint for T Cell Metabolism and Regulates Disease Tolerance in TB

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

Variations in Lung Anatomy Associated with COPD

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

BCG Educates Stem Cells for Protective Innate Immunity Against TB

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

Mechanical Ventilation Induces Diaphragmatic Dysfunction in Duchenne Muscular Dystrophy Mice

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

RIPK3 Protein is Involved in the Regulation of Immune Response to the Flu

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

STAT6- Inhibitory Peptide May Reduce Incidence of RSV-Related Asthma

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

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

Benefits of Newborn Screening for Cystic Fibrosis

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

First Proof That Mechanical Ventilation Can Cause Human Diaphragm Dysfunction

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

Toll-like Receptor Signalling in Regenerative Myogenesis: Friend and Foe

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

STAT6 Inhibitory Peptide Educated the Immune System From Developing an Allergic Response

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

Variants of Pseudomonas aeruginosa Can Cause a Lot of Inflammation

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

Nurturing Nanotubes: Role of Nanotubes Between T Cells and Airway Smooth Muscle

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

T Cells and Airway Smooth Muscle Interactions in Asthma

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

STAT-6 Inhibitory Peptide Inhibits Aberrant Th2 Responses in RSV Infection

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

Inhibition of PGE2 Increases Survival of Mice Infected With H1N1 Flu Virus

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

Starved Bacteria Can Better Adapt and Survive

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

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.

Meakins-Christie Laboratories Founded

August 1, 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.