CDK INHIBITION THERAPY AND POTENTIAL FOR NOVEL IMAGING BIOMARKERS IN IDIOPATHIC PULMONARY FIBROSIS

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Inflammation Research

Abstract

Idiopathic pulmonary fibrosis (IPF) affects some 4000 people a year in the UK. There is no effective therapy and the average survival is 3 years. This means that IPF has a worse prognosis than many common cancers. We do not know what causes the disease, but inflammation is part of the complex disease process. The neutrophil is an inflammatory blood cell present in excess amounts in the lungs of patients with IPF. Normally, neutrophils only live for a few hours before dying and being removed by ?clearing? cells. In some diseases such as IPF, we believe that the neutrophil is able to survive longer in the lung, thereby injuring tissue and cause scarring. Corticosteroids are powerful anti-inflammatory drugs that are often used, but appear to not work well in IPF.

Over the last 20 years, our group have studied how neutrophils are able to survive longer and crucially how we might overcome this to allow normal healing. We have now discovered that R-roscovitine, a drug that affects the cell survival, has the unique property of forcing activated neutrophils to die therefore preventing lung damage. R-roscovitine has been used recently in patients with cancers, since it may also be effective at killing tumour cells. These cancer studies show that the drug is safe to use in humans. We wish to perform a study of R-roscovitine in patients with IPF. We will firstly determine the optimum oral dose and side-effect profile in 20 patients with IPF. Next, we will perform a study in 40 patients with IPF randomly allocated receive a combination of R-roscovitine, no specific treatment or corticosteroids. We will measure neutrophils in lung fluid via bronchoscopy (a telescope into the lungs). We will also employ a non-invasive technique for measuring lung inflammation, the PET scan, which is able to detect neutrophils in the lung using X-rays.

Here in Edinburgh we have a constellation of facilities to ensure this study can be performed effectively and safely. Our large specialist clinic in which we see patients with IPF is within the same building as a Clinical Trials Facility with expertise in running trials of this nature. Adjacent to the main hospital is a state-of-the-art Research Institute in which the key discoveries of neutrophil survival and R-roscovitine properties were made, and which will house a PET scanning machine. These studies should provide the foundations for future definitive trials of R-roscovitine in IPF.

Technical Summary

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring of the lung with a median survival time from diagnosis of just 3 years, a poorer prognosis than for cancer of the breast, colon or ovary. There are 4000 new cases of IPF diagnosed annually and in the absence of a proven effective treatment, novel therapies are urgently required. Furthermore, there is a need to identify biomarkers of disease activity and progression. Although there are contentious theories regarding the pathogenesis of IPF, there is ample evidence that persistent inflammation is an important component of disease pathogenesis. Our group has generated a unifying body of supportive evidence to show that normal inflammatory resolution is dependent upon neutrophil apoptosis, a process that is delayed an inflammatory milieu in situ; corticosteroids rather than overcoming inflammation-enhanced survival, actually retard neutrophil apoptosis. We have now identified that the CDK-inhibitor R-roscovitine exhibits the as yet unique property of over-riding pro-survival inflammatory signals and driving neutrophil apoptosis. We have shown in vivo that R-roscovitine promotes neutrophil apoptosis, enhances resolution of inflammation and attenuates lung injury in the bleomycin model of lung fibrosis.
Early human studies of R-roscovitine have demonstrated its safety in patients with cancer, and here we propose a novel experimental medicine study of R-roscovitine in patients with IPF. We will firstly undertake a phase 1 study to establish the pharmacokinetics, safety and suitable dosing regime of oral R-roscovitine in prevalent cases of IPF. Guided by data from this study, we propose a small (n=40) factorial design phase 2 study to determine the efficacy of R-roscovitine in reducing lung neutrophil burden in incident patients with IPF. The primary end-point of the phase 2 study will be a neutrophil apoptotic index in bronchoalveolar lavage fluid. Furthermore consistent with the premise that these are experimental medicine studies, we will employ 18F-FDG PET, a marker of neutrophil activity, in this study with a view to qualifying this modality as a novel non-invasive biomarker in IPF.
In Edinburgh we have built a research team possessing considerable expertise in inflammatory cell biology, the mechanisms of inflammatory/scarring processes in human diseases and their experimental models, and the design and execution of clinical trials. This translational study is based on our original discovery of the previously unsuspected pro-resolution properties of R-roscovitine, and will be carried out in our established Interstitial Lung Disease Clinic under the auspices of the Wellcome Trust Clinical Research Facility.

Publications

10 25 50
 
Description BLF Project Grant
Amount £150,000 (GBP)
Organisation British Lung Foundation (BLF) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2010 
End 06/2012
 
Description Chief Scientists Office, Scotland
Amount £250,000 (GBP)
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 05/2012 
End 06/2013
 
Description Molecular endotyping lung fibrosis
Amount £80,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2017 
End 08/2020
 
Title Scottish Interstitial Lung Disease (ScILD) Gene and blood biobank 
Description Serial serum samples and bronchoalveolar lavage samples form patients with interstitial lung disease, including IPF. 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact nil yet 
 
Title Scottish Interstitial Lung Disease (ScILD) database 
Description A database/registry for idiopathic pulmonary fibrosis in Scotland designed to aid recruitment to clinical trials 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2009 
Provided To Others? Yes  
Impact The database has allowed other centres to recruit to IPF clinical trials that they may not otherwise have achieved. 
 
Title Edinburgh lung fibrosis cohort 
Description Unique cohort of incident consecutively presenting cases 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact Unique description of natural history of lung fibrosis 
 
Description Galecto 
Organisation Galecto Biotech
Country Sweden 
Sector Private 
PI Contribution Industry collaboration and partnership. Delivery of phase 1b clinical trial in IPF and mechanistic studies of galectin-3 inhibiton
Collaborator Contribution intellectual and financial contribution to clinical trial design and mechanistic studies
Impact nil yet
Start Year 2015
 
Description Many researchers in the MRC Centre of Inflammation University of Edinburgh 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution collaborator and mentors to many researchers - contributed to successful grant applications
Collaborator Contribution My collaborators provide significant intellectual input to my research team and effort.
Impact most of my publications feature other members of the MRC CIR UoE
Start Year 2006
 
Description UCB - The TGFbeta pathway in idiopathic pulmonary fibrosis 
Organisation UCB Pharma
Department UCB Celltech
Country United Kingdom 
Sector Private 
PI Contribution UCB wish to explore a TGFbeta-directed asset in IPF. Contract 1 was to assay TGFbeta-related mediators in lung lavage and serum from patients with IPF. My team provided that clinical samples and assay expertise. This project is ongoing. Contract 2 was to develop a 3D co-culture model of macrophages, fibroblasts and matrix in which to study TGFbeta pathways quantitively. This project employed Dr John Marwick in a collaborative project with Prof Neil Carragher (National Phenotypic Screening Centre) on a 6 month post-contract (with a view to longer-term funding)
Collaborator Contribution 1. Provision of funds to assay mediators and 12month technician post 2. Provision of 3D co-culture protocols
Impact limited output thus far.
Start Year 2016
 
Description 1. 13th London World Congress on Inflammation, July 8-12, 2017. Hilton London Metropole Hotel, London. GREMI (Groupe de Recherche et Etude des Médiateurs de l'Inflammation) Symposium. "Roscovitine as a new anti-inflammatory therapy promoting neutrophil apoptosis". 9th July 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 13th London World Congress on Inflammation, July 8-12, 2017. Hilton London Metropole Hotel, London. GREMI (Groupe de Recherche et Etude des Médiateurs de l'Inflammation) Symposium. "Roscovitine as a new anti-inflammatory therapy promoting neutrophil apoptosis". 9th July 2017.
Year(s) Of Engagement Activity 2017
URL http://wci2017.org
 
Description 1. British Society for Immunology Inflammation Affinity Group, in conjunction with the Manchester Immunology Group. Manchester at the "Inflammation and Disease" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact British Society for Immunology Inflammation Affinity Group, in conjunction with the Manchester Immunology Group. Manchester at the "Inflammation and Disease" conference on 9th -10th of September, 2014.
Year(s) Of Engagement Activity 2014
 
Description 1. Charles Darwin House, London, UK. Flow cytometric techniques for assessing apoptosis and efferocytosis of inflammatory cells. Advances in Cytometry 2015. The Terry Hoy Lecture, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Charles Darwin House, London, UK. Flow cytometric techniques for assessing apoptosis and efferocytosis of inflammatory cells. Advances in Cytometry 2015. The Terry Hoy Lecture, 13th November 2015
Year(s) Of Engagement Activity 2015
 
Description 1. ESCCA 2016, Edinburgh, UK. "Flow cytometric techniques for assessing apoptosis and efferocytosis of inflammatory cells: strategies for enhancing the resolution of inflammation. - A 'festival of cell analysis, apoptosis and inflammation' (11-14th September, 2016). Talk on the 14th September 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact ESCCA 2016, Edinburgh, UK. "Flow cytometric techniques for assessing apoptosis and efferocytosis of inflammatory cells: strategies for enhancing the resolution of inflammation. - A 'festival of cell analysis, apoptosis and inflammation' (11-14th September, 2016). Talk on the 14th September 2016.
Year(s) Of Engagement Activity 2016
 
Description 1. Edinburgh, SCRM. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" Wellcome Trust Site Visit, 5th August, 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact Edinburgh, SCRM. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" Wellcome Trust Site Visit, 5th August, 2016
Year(s) Of Engagement Activity 2016
 
Description 1. Pharmacology 2017, 11-13 December 2017, Queen Elizabeth II Conference Centre, London. The Japanese Pharmacological Society (JPS) and the British Pharmacological Society (BPS) Symposium. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 11th December 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Pharmacology 2017, 11-13 December 2017, Queen Elizabeth II Conference Centre, London. The Japanese Pharmacological Society (JPS) and the British Pharmacological Society (BPS) Symposium. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 11th December 2017.
Year(s) Of Engagement Activity 2017
URL https://www.bps.ac.uk
 
Description 1. Society for Reproductive Investigation (SRI); Scientific Symposium Targeting Inflammation to Improve Reproductive Health Across the Lifecourse (John McIntyre Conference Centre, Edinburgh, 16-18th August 2017). "Enhancing the resolution of inflammation as a potential therapeutic target in the reproductive system" 17th August 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Society for Reproductive Investigation (SRI); Scientific Symposium Targeting Inflammation to Improve Reproductive Health Across the Lifecourse (John McIntyre Conference Centre, Edinburgh, 16-18th August 2017). "Enhancing the resolution of inflammation as a potential therapeutic target in the reproductive system" 17th August 2017
Year(s) Of Engagement Activity 2017
URL https://www.ed.ac.uk/files/atoms/files/sri_programme_updated_14.8.2017.pdf
 
Description 11th World Congress on Inflammation, Natal RN, Brazil, September, 21-25, 2013. Invited speaker "Driving inflammatory cells apoptosis to resolve inflammation". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 11th World Congress on Inflammation, Natal RN, Brazil, September, 21-25, 2013. Invited speaker "Driving inflammatory cells apoptosis to resolve inflammation". Scheduled 24th Sept, 2013
Year(s) Of Engagement Activity 2013
 
Description 16th ANCA and Vasculitis Meeting, Paris, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 16th ANCA and Vasculitis Meeting, Paris, 14-17th April 2013. Plenary lecture entitled "Apoptosis, apoptotic cell clearance and resolution of inflammation"
Year(s) Of Engagement Activity 2013
URL http://www.sciencedirect.com/science/journal/07554982/42/4
 
Description 55th International Conference on the Bioscience of Lipids. Aberdeen, Scotland. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 55th International Conference on the Bioscience of Lipids. Aberdeen, Scotland. June 23-27th 2014. Invited speaker- plenary session.
Year(s) Of Engagement Activity 2014
URL http://conference.researchbib.com/view/event/36404
 
Description 7th Munster Immunology meeting Keynote speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 7th Munster Immunology meeting. Theme: Growing diversity in the Immune System. Keynote speaker talk entitled "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" 29th November 2019.
Year(s) Of Engagement Activity 2019
 
Description Banff, Canada 2017. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 10th Biennial Banff Inflammation Workshop (26-29th January 2017). Talk on 27th January 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Banff, Canada 2017. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 10th Biennial Banff Inflammation Workshop (26-29th January 2017). Talk on 27th January 2017.
Year(s) Of Engagement Activity 2017
URL https://www.ucalgary.ca/biw2017/
 
Description British Association Lung Research (BALR) Summer Meeting. Discovery to Recovery: still lost in translation? Queens University, Belfast. 30th August-1st September 2017. Zebrafish and mouse models of 'lung' inflammation - pros and cons! 31st August 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact British Association Lung Research (BALR) Summer Meeting. Discovery to Recovery: still lost in translation? Queens University, Belfast. 30th August-1st September 2017. Zebrafish and mouse models of 'lung' inflammation - pros and cons! 31st August 2017
Year(s) Of Engagement Activity 2017
URL https://www.balr.co.uk
 
Description Cardiff University, Cardiff School of Dentistry. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 3rd March 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Cardiff University, Cardiff School of Dentistry. "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration". 3rd March 2017.
Year(s) Of Engagement Activity 2017
 
Description Convegno su Nuove Prospettive in Chimica Farmaceutica (NPCF7), Savigliano, Italy, 29-31 May 2013. Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Convegno su Nuove Prospettive in Chimica Farmaceutica (NPCF7), Savigliano, Italy, 29-31 May 2013. Keynote Lecture "An introduction to the initiation, propagation and resolution of inflammation: Targeting the resolution of inflammation by pharmacological intervention" 20 May, 2013
Year(s) Of Engagement Activity 2013
 
Description Foz do Iguazu, Brazil. "Pharmacological strategies to enhance the resolution of inflammation" 48th Brazilian Congress of Pharmacology and Experimental Therapeutics and the 21st Latin American Congress of Pharmacology (47th October 2016). Talk on the 6th October 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Foz do Iguazu, Brazil. "Pharmacological strategies to enhance the resolution of inflammation" 48th Brazilian Congress of Pharmacology and Experimental Therapeutics and the 21st Latin American Congress of Pharmacology (47th October 2016). Talk on the 6th October 2016.
Year(s) Of Engagement Activity 2016
URL http://www.socesfar.es/index.php/our-services-4/our-services-5/our-services-9/250-48-brazilian-congr...
 
Description Goethe University, Translation Research Innovation- Pharma, Frankfurt. "Resolution of Inflammation" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Goethe University, Translation Research Innovation- Pharma, Frankfurt. "Resolution of Inflammation" 6th July 2015
Year(s) Of Engagement Activity 2015
 
Description Heriot-Watt University, School of Life Science, Edinburgh, UK. "Strategies for enhancing the resolution of inflammation" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Heriot-Watt University, School of Life Science, Edinburgh, UK. "Strategies for enhancing the resolution of inflammation" 25th November, 2015
Year(s) Of Engagement Activity 2015
 
Description IUPHAR, Edinburgh, 2016. "Pharmacological strategies to enhance the resolution of inflammation. NC-IUPHAR and BPS Focused Meeting on the Guide to Immunopharmacology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact IUPHAR, Edinburgh, 2016. "Pharmacological strategies to enhance the resolution of inflammation. NC-IUPHAR and BPS Focused Meeting on the Guide to Immunopharmacology (9-10th April, 2016). Talk on the 9th April 2016.
Year(s) Of Engagement Activity 2016
 
Description MRC Centre for Inflammation away day, Appleton Tower, Edinburgh. "Therapeutic Strategies to Enhance the Resolution of Inflammation to Promote Tissue Repair and Regeneration". 29th June 2017 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact MRC Centre for Inflammation away day, Appleton Tower, Edinburgh. "Therapeutic Strategies to Enhance the Resolution of Inflammation to Promote Tissue Repair and Regeneration". 29th June 2017
Year(s) Of Engagement Activity 2017
URL https://www.ed.ac.uk/inflammation-research
 
Description Nature Reviews Immunology. Resolving Inflammation conference 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Nature Reviews Immunology. Resolving Inflammation: Mechanisms and Drug Discovery, Keble College, Oxford, UK. April 1-3, 2012. Talk entitled "Targeting inflammatory cell apoptosis to resolve inflammation". Invited speaker in plenary session.

URL- http://www.nature.com/content/conferences/23393-02.html?WT.i_dcsvid=%%LIST_ID%%-%%RECIPIENT_ID%%&WT.ec_id=MARKETING
Year(s) Of Engagement Activity 2012
 
Description Novartis Institutes for BioMedical Research, Autoimmunity, Transplantation & Inflammation Disease Area, Basel, Switzerland. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Novartis Institutes for BioMedical Research, Autoimmunity, Transplantation & Inflammation Disease Area, Basel, Switzerland. "Apoptosis, Efferocytosis and the Resolution of Inflammation". 6th May 2014.
Year(s) Of Engagement Activity 2014
 
Description Our papers are frequently highlighted in the press 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A list of manuscript published by my research team and collaborators that have been highlighted in the University websites and twitter accounts and the general press are listed below (some examples of media outlets have been given).

Dorward DA, Felton JM, Robb CT, Craven T, Kipari T, Walsh TS, Haslett C, Kefala K, Rossi AG, Lucas CD. The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome. Thorax. 2017 Feb;72(2):182-185. doi: 10.1136/thoraxjnl-2016-209229. PubMed PMID: 27965411; PubMed Central PMCID: PMC5284332.

http://science.newsln.jp/news/2016110315440074.html
https://scifeeds.com/news/immune-cell-insight-offers-hope-for-tackling-deadly-lung-condition/

Hoodless LJ, Lucas CD, Duffin R, Denvir MA, Haslett C, Tucker CS, Rossi AG. Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo. Sci Rep. 2016 Nov 11;5:36980. dei: 10.1038/srep36980. PubMed PMID: 27833165; PubMed Central PMCID: PMC5105078.

http://www.eveningtimes.co.uk/news/14987467.Zebrafish_used_by_Scots_scientists_to_help_study_new_therapies_for_lung_disorders/
http://www.heraldscotland.com/news/14987467.Zebrafish_used_by_Scots_scientists_to_help_study_new_therapies_for_lung_disorders/
http://scientists.trendolizer.com/2017/01/zebrafish-used-by-scots-scientists-to-help-study-new-therapies-for-lung-disorders.html


Brook M, Tomlinson GH, Miles K, Smith RW, Rossi AG, Hiemstra PS, van 't Wout EF, Dean JL, Gray NK, Lu W, Gray M. Neutrophil-derived alpha defensives control inflammation by inhibiting macrophage mRNA translation. Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4350-5. dei: 10.1073/pnas.1601831113. PubMed PMID: 27044108; PubMed Central PMCID: PMC4843457.

http://immunitytales.com/a-molecular-brake-for-macrophage-driven-inflammation/
https://scifeeds.com/journal-article/neutrophil-derived-alpha-defensins-control-inflammation-by-inhibiting-macrophage-mrna-translation/
https://www.sciencedaily.com/releases/2016/04/160418120337.htm
http://www.ed.ac.uk/news/2016/arthritis-treatment-hope
http://www.dailymail.co.uk/health/article-3546735/Treatments-halt-pain-arthritis-set-developed-discovery-body-s-defence-switched-against-condition.html

Duffin R, O'Connor RA, Crittenden S, Forster T, Yu C, Zheng X, Smyth D, Robb CT, Rossi F, Skouras C, Tang S, Richards J, Pellicoro A, Weller RB, Breyer RM, Mole DJ, Iredale JP, Anderton SM, Narumiya S, Maizels RM, Ghazal P, Howie SE, Rossi AG, Yao C. Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science. 2016 Mar 18;351(6279):1333-8. dos: 10.1126/science.aad9903. PubMed PMID: 26989254; PubMed Central PMCID: PMC4841390

https://www.eurekalert.org/pub_releases/2016-03/uoe-iss031616.php
https://www.sciencedaily.com/releases/2016/03/160317150759.htm
http://www.sciencecodex.com/immune_study_shows_how_gut_keeps_deadly_infections_at_bay-178187
http://www.ebiotrade.com/newsf/2016-3/2016317131115664.htm

Marwick JA, Dorward DA, Lucas CD, Jones KO, Sheldrake TA, Fox S, Ward C, Murray J, Brittan M, Hirani N, Duffin R, Dransfield I, Haslett C, Rossi AG. Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments. J Leukoc Biol. 2013 Dec;94(6):1285-92. doi: 10.1189/jlb.0912462. PubMed PMID: 23964116; PubMed Central PMCID: PMC3855024.

https://bionews-tx.com/news/2014/03/12/chronic-bronchitis-emphysema-lung-disease-drug-ineffectiveness-explained-in-new-study/
https://stv.tv/news/east-central/266592-new-treatment-for-lung-diseases-a-step-closer-after-breakthrough/
https://m.medicalxpress.com/news/2013-12-oxygen-decrease-effectiveness-anti-inflammatory-therapies.html

Wheatley PS, Butler AR, Crane MS, Fox S, Xiao B, Rossi AG, Megson IL, Morris RE. NO-releasing zeolites and their antithrombotic properties. J Am Chem Soc. 2006 Jan 18;128(2):502-9. PubMed PMID: 16402837.

https://www.newscientist.com/article/mg18524856-700-pollution-fighter-turns-clot-buster/

Fox S, Wilkinson TS, Wheatley PS, Xiao B, Morris RE, Sutherland A, Simpson AJ, Barlow PG, Butler AR, Megson IL, Rossi AG. NO-loaded Zn(2+)-exchanged zeolite materials: a potential bifunctional anti-bacterial strategy. Acta Biomater. 2010 Apr;6(4):1515-21. toi: 10.1016/j.actbio.2009.10.038. PubMed PMID: 19861185.

http://www.ed.ac.uk/news/all-news/superbugs-231109
https://www.healthcanal.com/medical-breakthroughs/4056-new-chemical-may-play-key-role-in-hospital-superbugs-battle.html


Duffin R, Leitch AE, Sheldrake TA, Hallett JM, Meyer C, Fox S, Alessandri AL, Martin MC, Brady HJ, Teixeira MM, Dransfield I, Haslett C, Rossi AG. The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1. FEBS Lett. 2009 Aug 6;583(15):2540-6. dos: 10.1016/j.febslet.2009.07.017. PubMed PMID: 19616548.

http://news.bbc.co.uk/1/hi/scotland/edinburgh_and_east/8403307.stm
https://www.sciencedaily.com/releases/2009/12/091209113846.htm
http://www.nursinginpractice.com/article/cancer-drug-may-work-asthma

Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, Caldicott A, Martinez-Losa M, Walker TR, Duffin R, Gray M, Crescenzi E, Martin MC, Brady HJ, Savill JS, Dransfield I, Haslett C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med. 2006 Sep;12(9):1056-64.

https://www.sciencedaily.com/releases/2006/09/060903150749.htm
https://www.eurekalert.org/pub_releases/2006-09/uoe-kso090106.php


Mandal P, Chalmers JD, Graham C, Harley C, Sidhu MK, Doherty C, Govan JW, Sethi T, Davidson DJ, Rossi AG, Hill AT. Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial. Lancet Respir Med. 2014 Jun;2(6):455-63. doi: 10.1016/S2213-2600(14)70050-5. PubMed PMID: 24717640.

http://timesofindia.indiatimes.com/india/Statins-may-help-lung-disease-patients-as-well/articleshow/32674629.cms
http://www.scotsman.com/news/health/statins-may-help-those-with-lung-conditions-1-3351544
https://www.nursingtimes.net/statins-could-help-lung-patients/5069233.article?blocktitle=News-archive&contentID=700
http://www.business-standard.com/article/news-ani/cholesterol-lowering-drug-statins-could-ease-coughing-in-lung-disease-patients-114032500284_1.html
http://www.dailymail.co.uk/news/article-2587635/Doctors-fears-statins-putting-lives-risk-Professor-says-unjustified-concerns-effects-mean-drugs-not-prescribed-enough.html
http://www.heraldscotland.com/news/13152003.Statins_shown_to_help_with_chronic_coughing/
http://www.scienceworldreport.com/articles/13653/20140325/statin-cholesterol-lowering-drug-offers-relief-from-chronic-lung-disease.htm
Year(s) Of Engagement Activity 2006,2009,2010,2013,2014,2016,2017
 
Description Pharmacology, Toxicology and Therapeutics Seminar, University of Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Pharmacology, Toxicology and Therapeutics Seminar, "Killing inflammatory cells to resolve inflammation" Monday 5th November 2012, University of Edinburgh, QMRI.
Year(s) Of Engagement Activity 2012
 
Description R&D Systems Symposium "The Role of Cytokines and Signalling in Inflammation". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact R&D Systems Symposium "The Role of Cytokines and Signalling in Inflammation". Research Centre CAESAR, Ludwig-Erhard-Allee 2, 53175 Bonn. 15th October 2013.
Year(s) Of Engagement Activity 2013
 
Description THE PETER E. DRESEL MEMORIAL LECTURE IN PHARMACOLOGY 31st March 2015, Halifax, Canada. March 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact THE PETER E. DRESEL MEMORIAL LECTURE IN PHARMACOLOGY 31st March 2015, Halifax, Canada. March. This was a prestigious yearly award in honour of Prof Dresel,
Year(s) Of Engagement Activity 2015
 
Description The Banff Inflammation Workshop, Banff, Canada. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The Banff Inflammation Workshop, Banff, Canada, (31 Jan - 3 Feb 2013). Invited speaker and plenary lecture '"Resolution solutions!". 1st Feb 2013
Year(s) Of Engagement Activity 2013
URL http://www.ucalgary.ca/irn/meeting/banff-inflammation-workshop-2013
 
Description UCB, Slough, UK. "Targeting neutrophil apoptosis to resolve lung inflammation" 3rd November 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact UCB, Slough, UK. "Targeting neutrophil apoptosis to resolve lung inflammation" 3rd November 2016.
Year(s) Of Engagement Activity 2016
 
Description University of Aberdeen, Scottish Society of Cytomics SCC 2014. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact University of Aberdeen, Scottish Society of Cytomics SCC 2014. "Flow cytometric techniques for isolating and analysing leucocytes" 25-26th Sept 2014.
Year(s) Of Engagement Activity 2014
 
Description University of Edinburgh, Edinburgh-Zhejiang Joint Symposium 2014. Resolving lung inflammation, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact University of Edinburgh, Edinburgh-Zhejiang Joint Symposium 2014. Resolving lung inflammation, 3rd Sept 2014
Year(s) Of Engagement Activity 2014
 
Description University of Edinburgh. Edinburgh Infectious Disease Conference "Resolution of Inflammation: Implications for Infectious Diseases" 20th May 2015. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact University of Edinburgh. Edinburgh Infectious Disease Conference "Resolution of Inflammation: Implications for Infectious Diseases" 20th May 2015.
Year(s) Of Engagement Activity 2015
 
Description University of Edinburgh. QMRI, Public lecture "Treating injured lungs by extinguishing inflammation". Feb 11th 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact University of Edinburgh. QMRI, Public lecture "Treating injured lungs by extinguishing inflammation". Feb 11th 2015
Year(s) Of Engagement Activity 2015
 
Description University of Milan, Resolution of Inflammation in Pulmonary Diseases , 24th March 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact University of Milan, Resolution of Inflammation in Pulmonary Diseases , 24th March 2015
Year(s) Of Engagement Activity 2015
 
Description University of Sheffield, UK. Lecture in honour of Prof Moira Whyte 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact University of Sheffield, UK. Lecture in honour of Prof Moira Whyte 'Modulation Of Inflammation Resolution & Apoptosis' June 25th 2014.
Year(s) Of Engagement Activity 2014
 
Description school visit, edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact around 60 school children aged 7-11. their attention was captured by video images of englufing cells

there are plans to repeat this excercise
Year(s) Of Engagement Activity 2009,2010,2014,2017