Imperial College London
Portrait Picture

DrMarkBirrell

Faculty of Medicine, National Heart & Lung Institute

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 8578m.birrell

 
 
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Location

 

103Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

120 results found

Raemdonck K, de Alba J, Birrell MA, Grace M, Maher SA, Irvin CG, Fozard JR, O'Byrne PM, Belvisi MGet al., 2012, A role for sensory nerves in the late asthmatic response, THORAX, Vol: 67, Pages: 19-25, ISSN: 0040-6376

Journal article

Buckley J, Birrell MA, Maher SA, Nials AT, Clarke DL, Belvisi MGet al., 2011, EP<sub>4</sub> receptor as a new target for bronchodilator therapy, THORAX, Vol: 66, Pages: 1029-1035, ISSN: 0040-6376

Journal article

Birrell MA, Nials AT, 2011, At last, a truly selective EP2 receptor antagonist, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 164, Pages: 1845-1846, ISSN: 0007-1188

Journal article

Belvisi MG, Dubuis E, Birrell MA, 2011, Transient Receptor Potential A1 Channels Insights Into Cough and Airway Inflammatory Disease, CHEST, Vol: 140, Pages: 1040-1047, ISSN: 0012-3692

Journal article

Eltom S, Stevenson CS, Rastrick J, Dale N, Raemdonck K, Wong S, Catley MC, Belvisi MG, Birrell MAet al., 2011, P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke, PLoS ONE, Vol: 6, ISSN: 1932-6203

Chronic Obstructive Pulmonary Disease (COPD) is a cigarette smoke (CS)-driven inflammatory airway disease with anincreasing global prevalence. Currently there is no effective medication to stop the relentless progression of this disease. Ithas recently been shown that an activator of the P2X7/inflammasome pathway, ATP, and the resultant products (IL-1b/IL18) are increased in COPD patients. The aim of this study was to determine whether activation of the P2X7/caspase 1pathway has a functional role in CS-induced airway inflammation. Mice were exposed to CS twice a day to induce COPD-likeinflammation and the role of the P2X7 receptor was investigated. We have demonstrated that CS-induced neutrophilia in apre-clinical model is temporally associated with markers of inflammasome activation, (increased caspase 1 activity andrelease of IL-1b/IL-18) in the lungs. A selective P2X7 receptor antagonist and mice genetically modified so that the P2X7receptors were non-functional attenuated caspase 1 activation, IL-1b release and airway neutrophilia. Furthermore, wedemonstrated that the role of this pathway was not restricted to early stages of disease development by showing increasedcaspase 1 activation in lungs from a more chronic exposure to CS and from patients with COPD. This translational datasuggests the P2X7/Inflammasome pathway plays an ongoing role in disease pathogenesis. These results advocate thecritical role of the P2X7/caspase 1 axis in CS-induced inflammation, highlighting this as a possible therapeutic target incombating COPD.

Journal article

Belvisi MG, Dale N, Birrell MA, Canning BJet al., 2011, Bronchodilator activity of bitter tastants in human tissue, NATURE MEDICINE, Vol: 17, Pages: 776-776, ISSN: 1078-8956

Journal article

Birrell MA, Eltom S, 2011, The role of the NLRP3 Inflammasome in the pathogenesis of airway disease, PHARMACOLOGY & THERAPEUTICS, Vol: 130, Pages: 364-370, ISSN: 0163-7258

Journal article

Stevenson CS, Birrell MA, 2011, Moving towards a new generation of animal models for asthma and COPD with improved clinical relevance, PHARMACOLOGY & THERAPEUTICS, Vol: 130, Pages: 93-105, ISSN: 0163-7258

Journal article

Sadofsky LR, Boa AN, Maher SA, Birrell MA, Belvisi MG, Morice AHet al., 2011, TRPA1 is activated by direct addition of cysteine residues to the <i>N</i>-hydroxysuccinyl esters of acrylic and cinnamic acids, PHARMACOLOGICAL RESEARCH, Vol: 63, Pages: 30-36, ISSN: 1043-6618

Journal article

Buckley J, Birrell MA, Maher SA, Clarke DL, Nials A, Belvisi MGet al., 2011, EP4 Receptor Agonists: The Most Promising Novel Bronchodilator For Several Decades, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Rastrick JM, Eltom SM, Catley MC, Stevenson C, Adcock IM, Belvisi MG, Birrell MAet al., 2011, The In Vivo Characterisation Of An Acute And Sub-Chronic Model Of Cigarette Smoke-Induced Lung Inflammation, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Raemdonck K, Birrell MA, Belvisi MG, 2011, The Allergen Driven Late Asthmatic Response In Mice: A Role For Sensory Nerves And TRPA1, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Birrell MA, Van Oosterhout AJM, Belvisi MG, 2010, Do the current house dust mite-driven models really mimic allergic asthma?, EUROPEAN RESPIRATORY JOURNAL, Vol: 36, Pages: 1220-1221, ISSN: 0903-1936

Journal article

Freund-Michel VC, Birrell MA, Belvisi MG, 2010, Do β<sub>2</sub>-agonists inhibit capsaicin-induced cough?, EUROPEAN RESPIRATORY JOURNAL, Vol: 36, Pages: 460-461, ISSN: 0903-1936

Journal article

De Alba J, Raemdonck K, Dekkak A, Collins M, Wong S, Nials AT, Knowles RG, Belvisi MG, Birrell MAet al., 2010, House dust mite induces direct airway inflammation <i>in vivo</i>: implications for future disease therapy?, EUROPEAN RESPIRATORY JOURNAL, Vol: 35, Pages: 1377-1387, ISSN: 0903-1936

Journal article

Freund-Michel VC, Birrell MA, Giembycz MA, Hele DJ, Haj-Yahia S, Belvisi MGet al., 2010, β<sub>2</sub>-Agonists block tussive responses in guinea pigs <i>via</i> an atypical cAMP-dependent pathway, EUROPEAN RESPIRATORY JOURNAL, Vol: 35, Pages: 647-654, ISSN: 0903-1936

Journal article

Maher SA, Grace MS, Birrell MA, Belvisi MGet al., 2010, Prostaglandin E<sub>2</sub>-Induced Sensory Nerve Activation Is Mediated By TRPA1 And TRPV1, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Raemdonck K, De Alba J, Birrell MA, Belvisi MGet al., 2010, A Role For Airway Sensory Nerves In The Allergen Induced Late Asthmatic Response In A Rat Model Of Allergic Asthma, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Birrell MA, Belvisi MG, Grace M, Sadofsky L, Faruqi S, Hele DJ, Maher SA, Freund-Michel V, Morice AHet al., 2009, TRPA1 Agonists Evoke Coughing in Guinea Pig and Human Volunteers, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 180, Pages: 1042-1047, ISSN: 1073-449X

Journal article

Maher SA, Birrell MA, Belvisi MG, 2009, Prostaglandin E<sub>2</sub> Mediates Cough via the EP<sub>3</sub> Receptor Implications for Future Disease Therapy, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 180, Pages: 923-928, ISSN: 1073-449X

Journal article

Belvisi MG, Mitchell JA, 2009, Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 158, Pages: 994-1003, ISSN: 0007-1188

Journal article

Wong S, Belvisi MG, Birrell MA, 2009, MMP/TIMP expression profiles in distinct lung disease models: implications for possible future therapies, Respiratory Research, Vol: 10, ISSN: 1465-9921

BackgroundThere is currently a vast amount of evidence in the literature suggesting that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathogenesis of inflammatory airways diseases, such as asthma and COPD. Despite this, the majority of reports only focus on single MMPs, often only in one model system. This study aimed to investigate the profile of an extensive range of MMP/TIMP levels in three different pre-clinical models of airways disease. These models each have a different and very distinct inflammatory profile, each exhibiting inflammatory characteristics that are similar to that observed in asthma or COPD. Since these models have their own characteristic pathophysiological phenotype, one would speculate that the MMP/TIMP expression profile would also be different.MethodsWith the use of designed and purchased MMP/TIMP assays, investigation of rat MMP-2, 3, 7|14 and TIMP-1|4 mRNA expression was undertaken by Real Time PCR. The three rodent models of airways disease investigated were the endotoxin model, elastase model, and the antigen model.ResultsIntriguingly, we demonstrated that despite the distinct inflammatory profile observed by each model, the MMP/TIMP expression profile is similar between the models, in that the same MMPs/TIMPs were observed to be generally increased or decreased in all three models. It could therefore be speculated that in a particular disease, it may be a complex network of MMPs, rather than an individual MMP, together with inflammatory cytokines and other mediators, that results in the distinct phenotype of inflammatory diseases, such as asthma and COPD.ConclusionWe believe our data may provide key information necessary to understand the role of various MMPs/TIMPs in different inflammatory airway diseases, and aid the development of more selective therapeutics without the side effect profile of current broad-spectrum MMP inhibitors.

Journal article

Belvisi MG, Hele DJ, 2009, Cough sensors. III. Opioid and cannabinoid receptors on vagal sensory nerves., Handb Exp Pharmacol, Pages: 63-76, ISSN: 0171-2004

Cough is a persistent symptom of many inflammatory airways' diseases. Cough is mediated by receptors sited on sensory nerves and then through vagal afferent pathways, which terminate in the brainstem respiratory centre. Cough is often described as an unmet clinical need. Opioids are the only prescription-based antitussives currently available in the UK. They possess limited efficacy and exhibit serious unwanted side effects, such as physical dependence, sedation, respiratory depression and gastrointestinal symptoms. There are three classical opioid receptors: the mu, kappa and delta receptors. Peripheral opioid receptors are sited on sensory nerves innervating the airways. A greater understanding of the role of the peripheral and centrally sited opioid receptors is necessary to allow the development of targeted treatments for cough. Because of the limited efficacy and the side-effect profile of the opioids, potential new treatments are sought to alleviate cough. One class of compounds that is currently under examination is the cannabinoids. Like the opioids, cannabinoids have peripheral and centrally sited receptors and also suffer from the blight of unwanted centrally mediated side effects such as sedation, cognitive dysfunction, tachycardia and psychotropic effects. Two cannabinoid receptors have been identified, the CB(1) and CB(2) receptors, and their distribution varies throughout the peripheral and central nervous system. Encouragingly, early studies with these compounds suggest that it may be possible to separate their antitussive activity from their centrally mediated side effects, with CB(2) agonists showing potential as putative new treatments for cough. In this chapter, we describe the opioid and cannabinoid receptors, their distribution and the effects they mediate. Moreover, we highlight their potential advantages and disadvantages in the treatment of cough.

Journal article

Belvisi MG, Patel HJ, Freund-Michel V, Hele DJ, Crispino N, Birrell MAet al., 2008, Inhibitory activity of the novel CB<sub>2</sub> receptor agonist, GW833972A, on guinea-pig and human sensory nerve function in the airways, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 155, Pages: 547-557, ISSN: 0007-1188

Journal article

Birrell MA, De Alba J, Catley MC, Hardaker E, Wong S, Collins M, Clarke DL, Farrow SN, Willson TM, Collins JL, Belvisi MGet al., 2008, Liver X receptor agonists increase airway reactivity in a model of asthma via increasing airway smooth muscle growth, JOURNAL OF IMMUNOLOGY, Vol: 181, Pages: 4265-4271, ISSN: 0022-1767

Journal article

Freund-Michel VC, Birrell MA, Patel HJ, Murray-Lyon IM, Belvisi MGet al., 2008, Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases, EUROPEAN RESPIRATORY JOURNAL, Vol: 32, Pages: 579-584, ISSN: 0903-1936

Journal article

Catley MC, Birrell MA, Hardaker EL, de Alba J, Farrow S, Haj-Yahia S, Belvisi MGet al., 2008, Estrogen receptor β:: Expression profile and possible anti-inflammatory role in disease, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol: 326, Pages: 83-88, ISSN: 0022-3565

Journal article

Belvisi MG, Hele DJ, 2008, Peroxisome proliferator-activated receptors as novel targets in lung disease, CHEST, Vol: 134, Pages: 152-157, ISSN: 0012-3692

Journal article

Belvisi MG, 2008, Preclinical assessment of novel therapeutics on the cough reflex: Cannabinoid agonists as potential antitussives, LUNG, Vol: 186, Pages: S66-S69, ISSN: 0341-2040

Journal article

Mark A Birrell, Sissie Wong, Matthew C Catley, Maria G Belvisiet al., 2008, Impact of tobacco-smoke on key signalling pathways in the innate immune response in lung macrophages, Journal of Cellular Physiology

Journal article

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