MICA: Evaluation of anti diabetic drugs in the treatment of respiratory disease
Lead Research Organisation:
St George's, University of London
Department Name: Basic Medical Sciences
Abstract
The airways of the lung are lined with a thin layer of fluid (airway surface liquid, ASL) which is important for lung defence against infection. To optimise its function, the volume and composition of ASL are tightly regulated by the surface cells of the airway (epithelium). We have shown that the concentration of glucose (sugar) in ASL is normally much lower than that of blood. Our evidence indicates that this serves as a protective mechanism as glucose is a growth substrate for many organisms including infectious microbes. However, glucose concentration in ASL increases when the airways are inflamed, when blood glucose concentration is raised (hyperglycaemia, associated with diabetes or severe illness) and, more potently, when inflammation and hyperglycaemia are both present. This makes the airway more susceptible to infection particularly with pathogens such as methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.
We have developed a cell model of human airway epithelium to understand how glucose concentration in ASL is regulated. We have shown that glucose applied to the basolateral (blood) side can get across the epithelium into the ASL. Normally the movement of glucose between the epithelial cells is restricted. However, when the epithelium becomes inflamed, it becomes leakier allowing glucose to pass across it more easily. If this is coupled with increased glucose concentration on the basolateral side (as in diabetes), even more glucose gets across. In this situation, we showed that the growth of bacteria in ASL was increased. In an exciting new development, we prevented the growth of bacteria by treating the epithelium with metformin (a drug already in clinical use). Metformin predominantly acted to prevent glucose getting into ASL and supporting bacterial growth. This could potentially provide a new therapeutic route for treatment of lung disease particularly in the light of increased resistance of bacteria to antibiotic therapy.
It is difficult to investigate how inflammation and diabetes increase glucose in ASL in the lungs of human subjects. Therefore, we will use our cell model and animal models of human lung disease to gain an understanding of how this occurs. We will investigate whether metformin can reduce glucose concentrations in ASL and suppress respiratory infection. We will also investigate whether other drugs that are predicted to reduce glucose movement into ASL will have a similar effect. In addition, we will test whether new drugs that are being developed to reduce blood sugar levels in diabetes have an additive beneficial effect. This project will increase our understanding of how glucose is increased in ASL in lung disease and when blood sugar levels are raised and how these two events promote infection. It will also tell us whether metformin or other drugs that reduce glucose movement across the epithelium or reduce blood glucose could be used to treat patients with these conditions. This could have important economic and social impact particularly in wealthy countries where the ageing population is expanding, chronic illness is more prevalent and the incidence of diabetes is increasing.
We have developed a cell model of human airway epithelium to understand how glucose concentration in ASL is regulated. We have shown that glucose applied to the basolateral (blood) side can get across the epithelium into the ASL. Normally the movement of glucose between the epithelial cells is restricted. However, when the epithelium becomes inflamed, it becomes leakier allowing glucose to pass across it more easily. If this is coupled with increased glucose concentration on the basolateral side (as in diabetes), even more glucose gets across. In this situation, we showed that the growth of bacteria in ASL was increased. In an exciting new development, we prevented the growth of bacteria by treating the epithelium with metformin (a drug already in clinical use). Metformin predominantly acted to prevent glucose getting into ASL and supporting bacterial growth. This could potentially provide a new therapeutic route for treatment of lung disease particularly in the light of increased resistance of bacteria to antibiotic therapy.
It is difficult to investigate how inflammation and diabetes increase glucose in ASL in the lungs of human subjects. Therefore, we will use our cell model and animal models of human lung disease to gain an understanding of how this occurs. We will investigate whether metformin can reduce glucose concentrations in ASL and suppress respiratory infection. We will also investigate whether other drugs that are predicted to reduce glucose movement into ASL will have a similar effect. In addition, we will test whether new drugs that are being developed to reduce blood sugar levels in diabetes have an additive beneficial effect. This project will increase our understanding of how glucose is increased in ASL in lung disease and when blood sugar levels are raised and how these two events promote infection. It will also tell us whether metformin or other drugs that reduce glucose movement across the epithelium or reduce blood glucose could be used to treat patients with these conditions. This could have important economic and social impact particularly in wealthy countries where the ageing population is expanding, chronic illness is more prevalent and the incidence of diabetes is increasing.
Technical Summary
The respiratory tract is lined with a thin layer of fluid (airway surface liquid, ASL), which is important for lung defence against infection. Glucose concentrations in ASL are normally 12x lower than that of blood. However, they are raised in people during airway inflammation, hyperglycaemia and, more potently, when both are present, making the airway more susceptible to infection from pathogens such as methicillin-resistant S.aureus and P.aeruginosa.
We have shown in airway epithelial cells in vitro that, under normal conditions, glucose diffuses from blood into ASL but accumulation is limited by the permeability of the epithelium, blood glucose concentration, glucose uptake into the epithelial cell via GLUT transporters and its metabolism. Inflammation increased transepithelial permeability to glucose and elevated glucose in ASL. In addition, increasing basolateral glucose concentration increased glucose in ASL and promoted the growth of S.aureus on the apical surface of lung epithelial cells. In vitro, pre-treatment of airway epithelia with metformin (a drug used in the treatment of type II diabetes) reduced epithelial permeability to glucose and prevented the apical growth of S. aureus. Metformin had no direct effect on bacterial growth or on basolateral glucose concentration.
This project will investigate how lung glucose homeostasis is modified by inflammation and hyperglycaemia in vitro and in vivo. It will identify whether metformin inhibits glucose accumulation in ASL and limits the growth of respiratory pathogens in vivo. It will also investigate the therapeutic effect of other drugs which are reported to reduce epithelial permeability or reduce blood glucose concentrations. e.g. azithromycin, glucokinase activators and SGLT2 inhibitors. The outcomes of this project will determine whether these drugs have potential therapeutic benefit in the prevention and treatment of respiratory infection and chronic pulmonary disease.
We have shown in airway epithelial cells in vitro that, under normal conditions, glucose diffuses from blood into ASL but accumulation is limited by the permeability of the epithelium, blood glucose concentration, glucose uptake into the epithelial cell via GLUT transporters and its metabolism. Inflammation increased transepithelial permeability to glucose and elevated glucose in ASL. In addition, increasing basolateral glucose concentration increased glucose in ASL and promoted the growth of S.aureus on the apical surface of lung epithelial cells. In vitro, pre-treatment of airway epithelia with metformin (a drug used in the treatment of type II diabetes) reduced epithelial permeability to glucose and prevented the apical growth of S. aureus. Metformin had no direct effect on bacterial growth or on basolateral glucose concentration.
This project will investigate how lung glucose homeostasis is modified by inflammation and hyperglycaemia in vitro and in vivo. It will identify whether metformin inhibits glucose accumulation in ASL and limits the growth of respiratory pathogens in vivo. It will also investigate the therapeutic effect of other drugs which are reported to reduce epithelial permeability or reduce blood glucose concentrations. e.g. azithromycin, glucokinase activators and SGLT2 inhibitors. The outcomes of this project will determine whether these drugs have potential therapeutic benefit in the prevention and treatment of respiratory infection and chronic pulmonary disease.
Planned Impact
This project has potential to impact the public sector, commercial private sector and the wider public. We have identified a drug that has the potential to treat epithelial disease and reduce infection that is distinct from current antibiotic and steroid therapies therefore opening up new possibilities for academic and pharmaceutical research in the short term. Investigation of how this drug works in both in vitro and in vivo systems will add to understanding of the function of epithelial tissues and aid identification of potential new targets for drug development for respiratory disease. This project will therefore directly impact scientists working in epithelia, inflammatory disease, infection and immunity and diabetes.
The main output of this study will be new insights into glucose homeostasis in airway epithelium and its role in preventing infection. As part of this study we will characterise the effects of hyperglycaemia on glucose homeostasis in in vitro and in vivo models of airway epithelial disease. We will use bacterial co-culture/infection techniques to investigate the effect of hyperglycaemia on the growth of respiratory pathogens. The in vitro model we have developed will provide a useful tool for initial drug screening in development of non-antibiotic drugs to prevent lung infection and meets the principles of the 3Rs (Replacement, Refinement and Reduction). We are working with Astra Zeneca to utilize their models of inflammatory lung disease to translate our in vitro findings. They will also provide drugs have been developed but not yet fully available to test in these systems. Their involvement will promote development and translation and therefore enhance impact in this area.
In the long term, we anticipate that understanding of the normal mechanisms that regulate glucose concentrations in the healthy airway, how factors associated with chronic disease and diabetes (prevalent in an ageing population) alter epithelial function and glucose homeostasis, together with the identification of drugs that prevent these effects, will ultimately benefit human and animal health with social and economic impact. Metformin is a drug already in clinical use with very few side effects. Understanding its action on epithelia and how this inhibits glucose flux and the growth of common pathogens such as S. aureus and Ps. aeruginosa provides a new and novel therapeutic mechanism and adds to the known activities of this drug. Data from this study will also add to the known activities of the other drugs studied. We anticipate that this knowledge will facilitate future assessment of the action of these drugs in vivo and translation into treatment could be rapid, with long term benefits to the wider public by enhancing quality of life and health. To enhance impact in this area we already have studies underway to investigate the effect of metformin on exacerbations in patients with chronic obstructive pulmonary disease. Prof. Baker also runs a patient advisory group, comprising patients and their carers who work collaboratively with researchers and clinicians to develop such projects. This group also provides advice for and a route of dissemination of results to patients.
We are currently the only research group in the UK investigating the role of glucose homeostasis in the lung. We are leading the world in this field, which, through publication and presentation of the data at international scientific meetings, is now receiving significant attention overseas. This industrial collaboration will increase impact in this area by aiding translation and development of this novel research into therapies. The success of this project and its future development could therefore contribute to the economic competitiveness of the UK.
The main output of this study will be new insights into glucose homeostasis in airway epithelium and its role in preventing infection. As part of this study we will characterise the effects of hyperglycaemia on glucose homeostasis in in vitro and in vivo models of airway epithelial disease. We will use bacterial co-culture/infection techniques to investigate the effect of hyperglycaemia on the growth of respiratory pathogens. The in vitro model we have developed will provide a useful tool for initial drug screening in development of non-antibiotic drugs to prevent lung infection and meets the principles of the 3Rs (Replacement, Refinement and Reduction). We are working with Astra Zeneca to utilize their models of inflammatory lung disease to translate our in vitro findings. They will also provide drugs have been developed but not yet fully available to test in these systems. Their involvement will promote development and translation and therefore enhance impact in this area.
In the long term, we anticipate that understanding of the normal mechanisms that regulate glucose concentrations in the healthy airway, how factors associated with chronic disease and diabetes (prevalent in an ageing population) alter epithelial function and glucose homeostasis, together with the identification of drugs that prevent these effects, will ultimately benefit human and animal health with social and economic impact. Metformin is a drug already in clinical use with very few side effects. Understanding its action on epithelia and how this inhibits glucose flux and the growth of common pathogens such as S. aureus and Ps. aeruginosa provides a new and novel therapeutic mechanism and adds to the known activities of this drug. Data from this study will also add to the known activities of the other drugs studied. We anticipate that this knowledge will facilitate future assessment of the action of these drugs in vivo and translation into treatment could be rapid, with long term benefits to the wider public by enhancing quality of life and health. To enhance impact in this area we already have studies underway to investigate the effect of metformin on exacerbations in patients with chronic obstructive pulmonary disease. Prof. Baker also runs a patient advisory group, comprising patients and their carers who work collaboratively with researchers and clinicians to develop such projects. This group also provides advice for and a route of dissemination of results to patients.
We are currently the only research group in the UK investigating the role of glucose homeostasis in the lung. We are leading the world in this field, which, through publication and presentation of the data at international scientific meetings, is now receiving significant attention overseas. This industrial collaboration will increase impact in this area by aiding translation and development of this novel research into therapies. The success of this project and its future development could therefore contribute to the economic competitiveness of the UK.
Organisations
- St George's, University of London (Lead Research Organisation, Project Partner)
- Francis Crick Institute (Collaboration)
- University College London (Collaboration)
- Technical University of Munich (Collaboration)
- Newcastle University (Collaboration)
- University of North Carolina at Chapel Hill (Collaboration)
- AstraZeneca (Collaboration)
- Epsom and St Helier University Hospitals NHS Trust (Collaboration)
- University College Cork (Collaboration)
- University of Ghent (Collaboration)
- Boehringer Ingelheim (Collaboration)
- University of Chicago (Project Partner)
- Imperial College London (Project Partner)
- AstraZeneca (United Kingdom) (Project Partner)
- University of North Carolina at Chapel Hill (Project Partner)
Publications
Baines D
(2013)
Kinases as targets for ENaC regulation.
in Current molecular pharmacology
Baines D
(2017)
Lung Epithelial Biology in the Pathogenesis of Pulmonary Disease
Baines DL
(2023)
Getting sweeter: new evidence for glucose transporters in specific cell types of the airway?
in American journal of physiology. Cell physiology
Baker EH
(2018)
Airway Glucose Homeostasis: A New Target in the Prevention and Treatment of Pulmonary Infection.
in Chest
Bearham J
(2021)
A modified fluorescent sensor for reporting glucose concentration in the airway lumen.
in PloS one
Bearham J
(2019)
Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycemia.
in American journal of physiology. Cell physiology
Gill SK
(2016)
Increased airway glucose increases airway bacterial load in hyperglycaemia.
in Scientific reports
Hitchings AW
(2016)
Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial.
in Thorax
Description | Cystic Fibrosis Strategic Research Centre |
Amount | £718,602 (GBP) |
Funding ID | SRC 006 |
Organisation | Cystic Fibrosis Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2016 |
End | 03/2019 |
Description | Indentification and characterisation of mechanisms to maintain and restore epithelial barrier integrity |
Amount | £249,049 (GBP) |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start | 06/2018 |
End | 07/2020 |
Description | MRC - London Intercollegiate Doctoral Training Partnership |
Amount | £105,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 03/2021 |
Description | MRC CASE studentship |
Amount | £106,000 (GBP) |
Funding ID | MR/L013509/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2018 |
Description | MRC London Intercollegiate Doctoral Training Partnership |
Amount | £105,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 03/2021 |
Description | No Scheme |
Amount | £240,508 (GBP) |
Organisation | AstraZeneca |
Department | Astra Zeneca |
Sector | Private |
Country | United States |
Start | 03/2018 |
End | 03/2020 |
Title | glucose sensors |
Description | We have developed several fluorescent glucose biosensors based on 1. Genetically encoded fluorophore linked to protein. 2. Environmental sensitive fluorophore covalently linked to protein. Some of these have now been catalogued for invention disclosure. |
Type Of Material | Technology assay or reagent |
Year Produced | 2018 |
Provided To Others? | No |
Impact | Potential impact for use as a tool to analyse glucose in airway, predict blood glucose, and as a research tool. Helassa N, Garnett JP, Farrant M, Khan F, Pickup JC, Hahn KM, MacNevin CJ, Tarran R, Baines DL. 2014 A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration. Biochem J. Sep 15. [Epub ahead of print] PMID: 25220254 |
Description | Astra Zeneca |
Organisation | AstraZeneca |
Department | Respiratory and Inflammation iMED Strategy team Mölndal |
Country | Sweden |
Sector | Private |
PI Contribution | Collaborator in MICA award 'Evaluation of anti diabetic drugs in the treatment of respiratory disease'. Collaboration continuing with joint MRC-CASE studentship, and funding for further Astra Zeneca led airway epithelia study, external supervisor for Astra Zeneca Postdoctoral Scientist, Key Opinion Leader. |
Collaborator Contribution | Collaborator in MICA award 'Evaluation of anti diabetic drugs in the treatment of respiratory disease'. Further funding for Astra Zeneca led project, access to facilities, chemicals and pharmaceutical insight. Joint supervision of MRC-CASE student. |
Impact | Holmberg CH, Astrand A, Wingren C, Garnett JP, Mayer G, Taylor JD, Baker EH... Baines DL. (2017). Differential Effect of LPS on Glucose, Lactate and Inflammatory Markers in the Lungs of Normal and DiabeticMice. Pulmonary and Respiratory Medicine Open Access 2017. Pulmonary and Respiratory Medicine Open Access 2017.,pp. PROA-101. Åstrand A, Wingren C, Benjamin A, Tregoning JS, Garnett JP, Groves H, Gill S, Orogo-Wenn M, Lundqvist AJ, Walters D, Smith DM, Taylor JD, Baker EH, Baines DL. Dapagliflozin-lowered blood glucose reduces respiratory P. aeruginosa infection in diabetic mice. Br J Pharmacol. 2017 May;174(9):836-847. doi: 10.1111/bph.13741. Epub 2017 Mar 9. |
Start Year | 2013 |
Description | Boehringer Ingelheim Pharma |
Organisation | Boehringer Ingelheim |
Country | Germany |
Sector | Private |
PI Contribution | Novel data relating to airway epithelial research . |
Collaborator Contribution | Access to technical expertise/equipment not available at home institution data from which contributed to publication. |
Impact | doi: 10.1038/srep37955 |
Start Year | 2015 |
Description | Chapel Hill Pharmacology |
Organisation | University of North Carolina at Chapel Hill |
Department | UNC School of Medicine |
Country | United States |
Sector | Academic/University |
PI Contribution | Development of fluorescent glucose sensor |
Collaborator Contribution | Provision of long wavelength fluorescent dyes |
Impact | Helassa N, Garnett JP, Farrant M, Khan F, Pickup JC, Hahn KM, MacNevin CJ, Tarran R, Baines DL. 2014 A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration. Biochem J. Sep 15. [Epub ahead of print] PMID: 25220254 Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H+ secretion. Garnett JP, Kalsi KK, Sobotta M, Bearham J, Carr G, Powell J, Brodlie M, Ward C, Tarran R, Baines DL. Sci Rep. 2016 Nov 29;6:37955. doi: 10.1038/srep37955. PMID:27897253 |
Start Year | 2013 |
Description | Francis Crick Institute - Airway basal cells |
Organisation | Francis Crick Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a strategic research centre funded by the Cystic Fibrosis trust which involves a partnership between researcher at the Frances Crick Institute. We carry out and provide data from functional experiments to support phenotype replication. |
Collaborator Contribution | Under the grant funding they provide human primary airway basal cells and culture optimisation for functional experiments. |
Impact | No outputs directly associated with this collaboration yet. Covers two disciplines cell biology, physiology. |
Start Year | 2017 |
Description | GLUT10 KO mice |
Organisation | University of Ghent |
Department | Department of Pediatrics and Medical Genetics |
Country | Belgium |
Sector | Academic/University |
PI Contribution | We are providing data on the effect of GLUT10 KO on the pathophysiology of the airway. This will contribute to our understanding of the function of GLUT10 as a glucose transporter and its role in arterial tortuosity syndrome. |
Collaborator Contribution | The provision of GLUT10 KO mice for the analysis of airway surface liquid, isolation of airway cells and tissue. |
Impact | Currently in process of sample collection, data acquisition and analysis. |
Start Year | 2015 |
Description | Glucose transporter knockout mice |
Organisation | Technical University of Munich |
Country | Germany |
Sector | Academic/University |
PI Contribution | 1. We are providing information on how GLUT 2/5 and SGLT1 KO in mice affects the pathophysiology of the airway. 2. We are providing samples that we collect from the airway to a potential study investigating how glucose transport affects the formation of metabolites in these animals. |
Collaborator Contribution | The partners are contributing the KO mice to the study for sample and tissue collection. |
Impact | Currently in the process of data collection and analysis for publication. |
Start Year | 2015 |
Description | Marsico lung Institute/Dept Cell Biology and Physiology |
Organisation | University of North Carolina at Chapel Hill |
Country | United States |
Sector | Academic/University |
PI Contribution | PhD student working on research question visited UNC. We provided a clear research question and data to support outcome. We provided expertise in CF gene therapy, codon optimised CFTR. We have prepared manuscript containing collaborative output and have submitted for publication. |
Collaborator Contribution | Providing technical expertise in ddPCR and analysis of mixed sex cell populations (non-CF and CF) by identification of sex determining AMELX or AMELY genes. |
Impact | Gain-of-function CFTR restores essential epithelial function with greater efficacy than wildtype or codon optimized CFTR when expressed in cystic fibrosis airway cells. Maximillian Woodall, Robert Tarran, Rhianna Lee, Hafssa Anfishi, Stella Prins, John Counsell, Paola Vergani, Stephen Hart, Deborah Baines. Molecular Therapy - Methods & Clinical Development, 2023 Aug 12;30:593-605. doi: 10.1016/j.omtm.2023.08.006. eCollection 2023 Sep 14.PMID: 37701179 Passaging Primary Human Bronchial Epithelia Reduces CFTR-Mediated Fluid Transport and Alters mRNA Expression. Tongde Wu, Joe A. Wrennall, Hong Dang, Deborah L. Baines & Robert Tarran. Cells 2023, 12(7), 997; https://doi.org/10.3390/cells12070997. Culture with apically applied healthy or disease sputum alters the airway surface liquid proteome and ion transport across human bronchial epithelial cells. Woodall M, Reidel B, Kesimer M, Tarran R, Baines DL. Am J Physiol Cell Physiol. 2021 Dec 1;321(6):C954-C963. doi: 10.1152/ajpcell.00234.2021. Epub 2021 Oct 6.PMID: 34613844 |
Start Year | 2018 |
Description | Marsico lung Institute/UNC Cystic Fibrosis Centre |
Organisation | University of North Carolina at Chapel Hill |
Department | UNC School of Medicine |
Country | United States |
Sector | Academic/University |
PI Contribution | How hyperglycaemia contributes to CF disease and effects of smoking on airway. Development of glucose sensor for use in vitro. |
Collaborator Contribution | Provision of primary cultures lung epithelial cells |
Impact | Helassa N, Garnett JP, Farrant M, Khan F, Pickup JC, Hahn KM, MacNevin CJ, Tarran R, Baines DL. 2014 A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration. Biochem J. Sep 15. [Epub ahead of print] PMID: 25220254 Garnett JP, Tarran R, Gray MA, Ward C, Brodlie M, Baker EH and Baines DL (2013). Elevated glucose flux across cystic fibrosis airway epithelium is an important factor for Pseudomonas aeruginosa growth in airway epithelial co-culture. PLoS ONE 8(10): e76283. doi:10.1371/journal.pone.0076283 |
Start Year | 2013 |
Description | Newcastle university |
Organisation | Newcastle University |
Department | Institute of Cellular Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in airway epithelial physiology |
Collaborator Contribution | Expertise in pH measurement |
Impact | doi: 10.1038/srep37955 |
Start Year | 2016 |
Description | South West Thames Institute of Renal Research |
Organisation | Epsom and St Helier University Hospitals NHS Trust |
Department | South West Thames Institute for Renal Research |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I co-supervise a funded PhD student I provide expertise in glucose transport across epithelial cells and the use of dapagliflozin. We are providing expertise and tools (created during this award) for extracellular glucose measurement I am a member of the management board |
Collaborator Contribution | They co-supervise a PhD student They are leading on grant applications for further funding for the use of dapagliflozin in renal disease |
Impact | PhD thesis and publication in preparation. Multidisciplinary clinical and scientific. |
Start Year | 2018 |
Description | UCL |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in ion transport measurement across airway cells |
Collaborator Contribution | Provision of primary airway epithelial cells (HBE) and transformed (HBE) |
Impact | Sucessful Cystic Fibrosis SRC bid and funding 2016 https://www.cysticfibrosis.org.uk/the-work-we-do/research/research-we-are-funding/strategic-research-centres/src-8-hart-gene-editing. Munye MM, Shoemark A, Hirst RA, Delhove JM, Sharp TV, McKay TR, O'Callaghan C, Baines DL, Howe SJ, Hart SJ (2016) BMI-1 extends proliferative potential of human bronchial epithelial cells whilst retaining their mucociliary differentiation capacity. Am J Physiol Lung Cell Mol Physiol. 2017 Feb 1;312(2):L258-L267. doi: 10.1152/ajplung.00471.2016. |
Start Year | 2016 |
Description | UCL |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in ion transport measurement across airway cells |
Collaborator Contribution | Provision of primary airway epithelial cells (HBE) and transformed (HBE) |
Impact | Sucessful Cystic Fibrosis SRC bid and funding 2016 https://www.cysticfibrosis.org.uk/the-work-we-do/research/research-we-are-funding/strategic-research-centres/src-8-hart-gene-editing. Munye MM, Shoemark A, Hirst RA, Delhove JM, Sharp TV, McKay TR, O'Callaghan C, Baines DL, Howe SJ, Hart SJ (2016) BMI-1 extends proliferative potential of human bronchial epithelial cells whilst retaining their mucociliary differentiation capacity. Am J Physiol Lung Cell Mol Physiol. 2017 Feb 1;312(2):L258-L267. doi: 10.1152/ajplung.00471.2016. |
Start Year | 2016 |
Description | University of Cork - gene editing |
Organisation | University College Cork |
Country | Ireland |
Sector | Academic/University |
PI Contribution | We are responsible for functional assessment of gene edited airway epithelial cells |
Collaborator Contribution | They have provided tools and reagents and expertise to genetically edit cells using CRISPR Cas9 technology. |
Impact | No outcomes yet |
Start Year | 2017 |
Title | Metformin treatment in COPD |
Description | A randomised, double-blind, placebo-controlled trial of metformin in chronic obstructive pulmonary disease (COPD) exacerbations: a pilot study |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2015 |
Development Status | Closed |
Clinical Trial? | Yes |
Impact | This intervention strategy with metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. |
URL | http://www.isrctn.com/ISRCTN66148745 |
Description | Invited Speaker |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited Speaker - Ion Channels in Health and Disease Conference, Doha, Quatar 2016. Presented talk on effect of hyperglycaemia in the lung. Diagnosis of Type II diabetes in young people is growing rapidly the middle east. There was much interest in the topic from professional practitioners and policy makers. |
Year(s) Of Engagement Activity | 2016 |
Description | Invited Speaker Physiological Society, University of St Andrews, UK. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker Membrane Transport 2023: Recent Research into Ion Channels, Transporters and Epithelial Physiology, University of St Andrews, UK. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.physoc.org/events/membrane-transport-2023-recent-research-into-ion-channels-transporters... |
Description | Invited speaker |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Physiological Society Topic Meeting -Physiology, pathophysiology and future treatment for diabetic complications. London 2015. Presented work from this grant which resulted in further debate about the consequences of diabetes and future treatment. |
Year(s) Of Engagement Activity | 2015 |
Description | Princes Teaching Institute |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Invitation to present a talk discussion on Transporters to a New Teacher Subject Day, Westminster. The purpose of the day was to provide up to date scientific information and insight to help teachers translate into classroom and enthuse students. This is now an ongoing appointment |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.princes-ti.org.uk/what-we-do/new-teacher-subject-days |
Description | Prize lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Ussing Prize Lecture at EB 2020 (Epithelial Transport Group) - postponed until 2021 |
Year(s) Of Engagement Activity | 2021 |
Description | Public Engagement Event |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | The event was Living with Type 1 Diabetes It sparked a lot of discussion and increased awareness about research and patient experience There were a lot of interesting question from staff and public. The event sparked public interest in future events |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.sgul.ac.uk/news/public-events |
Description | Schools visits (London) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 30 or more 15-18 year students attend talks on CF disease (AS/A2 module subject) or research. Ususally sparks discussion and leads to work experience placements at SGUL. Sparks discussion about research and entrance to biomedical/medical degree courses. Regularly leads to work experience placements at SGUL. |
Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013 |
Description | Spotlight on Science - Public Event |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | I organised a spotlight on Science public Event at St Georges - The Great Vape Debate. The event included presentations from scientists and advocates on the pros and cons of vaping. Discussion points were; use of vapes as smoking cessation tool, nicotine addiction, physiological harm, regulation. Surveys were taken before and after event. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.sgul.ac.uk/events/spotlight-on-science-the-great-vape-debate |
Description | Symposium organiser/Chair |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Symposia Bittersweet, sensing the environment and evoking physiological change, Joint America and British Physiological Societies, Dublin 2016 |
Year(s) Of Engagement Activity | 2016 |
Description | Symposium organiser/Chair |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I chaired a symposium on the physiological effects of electronic e.cigarette use - a Nasty Case of the Vapours. The symposium was well attended and received. It resulted in a series of reviews on the physiological effects of vaping and a Cross Talk debate on the pros and cons of vaping to be published in the Journal of Physiology in 2020. Much of this information will be promoted and openly accessible. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.physoc.org/events/physiology2019/ |
Description | U3A |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | 70 people attended the lecture, good discussion and questions after the event request for further speakers |
Year(s) Of Engagement Activity | 2014 |
Description | University of Surrey |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Invited speaker - working with vet school and other departments working on airway to generate of ideas for collaboration |
Year(s) Of Engagement Activity | 2023 |