Induction of neutrophil apoptosis and treatment of severe lung inflammation

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

Abstract

Inflammatory lung diseases like chronic bronchitis and emphysema (COPD) and scarring conditions are responsible for a huge burden of illness and untimely deaths in the UK, but current treatments are at best poorly-effective. Over the past twenty years we have been taking an alternative approach to harness the mechanisms by which some inflammatory responses are known to get better spontaneously. Specifically we have identified a mechanism by which key inflammatory cells called neutrophils can be made to commit suicide and be removed silently by local scavenger cells called macrophages. Unfortunately this suicide process is usually overcome by powerful survival factors present in the inflamed lung.
In work newly-published in the leading international medical science journal Nature Medicine we have shown that a CDK inhibitor called R-roscovitine, currently under clinical trial in cancer patients, causes a hitherto unexpected induction of neutrophil suicide, even in the presence of survival factors, and makes relevant models of human inflammatory lung disease resolve. This work has recently been publicised in the lay press.
In our proposed programme of research we will define exactly how this works, an approach which may lead to the discovery of other useful anti-inflammatory drugs. We will also carry out a clinical study of the drug s effectiveness using cutting-edge imaging technology to monitor the progress of the disease non-invasively and demonstrate its response to treatment.

Technical Summary

Inflammatory lung diseases like COPD, ARDS and interstitial lung diseases (ILD) are an MRC priority for research. Characterised by the persistent accumulation of neutrophils associated with architectural disruption and fibrosis, they are highly resistant to treatment with glucocorticoids and there is a pressing need to identify new therapies. However, under other circumstances even massive inflammatory responses can resolve spontaneously and completely, as exemplified by the dramatic resolution of the pulmonary inflammatory response in streptococcal pneumonia. We have been investigating the resolution mechanisms of inflammation with the aim of harnessing them for therapeutic benefit in inflammatory disease.
The neutrophil, specifically implicated in the pathogenesis of these diseases, was thought to meet its fate in situ by necrosis, despite the predictable histotoxic and pro-inflammatory consequences. Twenty years ago we discovered that the extravasated neutrophil undergoes apoptosis, whereby in contrast it shuts down secretion and is cleared intact by macrophages employing a novel recognition mechanism which fails to provoke release of pro-inflammatory mediators. In an investigative strategy designed to !Ydrive!
this cellular pathway in persistent inflammation, we demonstrated that inflammatory mediators like GM-CSF markedly retarded neutrophil apoptosis (a property shared with glucocorticoids; perhaps partly explaining their relative ineffectiveness in many inflammatory diseases). We then identified a variety of agents which induced granulocyte apoptosis in vitro, but their effects of were overridden by inflammatory mediators known to be present at inflamed sites. However, we have now shown that R-roscovitine and other CDK inhibitors not only induce apoptosis in stimulated inflammatory neutrophils by a mechanism involving down-regulation of the neutrophil survival factors Mcl-1 and XIAP but also dramatically enhance inflammatory resolution in clinically-relevant models of human lung disease.
In order to prove our hypothesis that the pro-resolution effects of CDK inhibitors are mediated specifically through the neutrophil s apoptotic machinery, we will now employ incisive tools (HIV-tat, siRNA and Cre-Lox) to identify CDKs of specific importance and dissect the roles of NFkB and Mcl-1 and other possible survival proteins of the Bcl-2 family in vitro, together with conditional knockouts of Mcl-1 and candidate CDKs in vivo. In parallel we will confirm the efficacy of CDK inhibitors, and demonstrate the value of 18F-FDG PET and other non-invasive biomarkers in murine bleomycin lung injury and in a randomised double-blind study of R-roscovitine (with and without glucocorticoids) of human IPF, in a new approach to the treatment of inflammatory diseases of the lung and other organs.

Publications

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Alessandri AL (2013) Resolution of inflammation: mechanisms and opportunity for drug development. in Pharmacology & therapeutics

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Banner KH (2009) Highlights of a workshop to discuss targeting inflammation in cystic fibrosis. in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

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Barth ND (2017) The "Phagocytic Synapse" and Clearance of Apoptotic Cells. in Frontiers in immunology

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Bedi P (2018) Blood Neutrophils Are Reprogrammed in Bronchiectasis in American Journal of Respiratory and Critical Care Medicine

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Bournazou I (2010) Inhibition of eosinophil migration by lactoferrin. in Immunology and cell biology

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Bournazou I (2009) Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. in The Journal of clinical investigation

 
Description MRC Programme Grant
Amount £2,500,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2013 
End 10/2018
 
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 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 1. University of Adriano Rossi invited to give plenary talk. Birmingham, Symposium of Mechanism of Inflammation (Wellcome Trust Mechanisms of Inflammatory Diseases PhD Programme). Plenary presentation "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" 5th Oct 2018 
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 University of Birmingham, Symposium of Mechanism of Inflammation (Wellcome Trust Mechanisms of Inflammatory Diseases PhD Programme). Plenary presentation "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" 5th Oct 2018


AGR Invited to join the Wellcome Trust DTP on Inflammatory Disease Advisory Board for the programme.
Year(s) Of Engagement Activity 2018
 
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 AGR invited speaker. St. George's University of London Seminar. Invited seminar entitled "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" Seminar on the 26th October 2018 
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
Year(s) Of Engagement Activity 2018
 
Description AGR keynote speaker. Banff, Alberta, Canada. Invited presentation "Inflammation resolution: An evolutionary conserved process". 11th Biennial Banff Inflammation Workshop (24-27th January 2019). Talk on 26th January 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Aimed at researchers and postgraduate - scientific collaborations and research discussed.
Year(s) Of Engagement Activity 2019
 
Description Adriano Rossi - Invited speaker - Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA. Presentation for the Cleveland IDEAS symposium on September 16-18, 2018. Invited presentation "Resolving Inflammation to Enhance Tissue Repair in the Lung: Implications for the Gut. Talk on the 18th Sept 2018 
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 aimed at researchers to generate new ideas and approaches in the field of gastoenetrology
Year(s) Of Engagement Activity 2018
 
Description Adriano Rossi - invited speaker. Heriot-Watt University, NC3Rs Symposium. Presentation entitled "Cellular and mechanistic processes linking inflammation and tissue repair: use of zebrafish larvae" Talk on the 14th May 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact NC3R grant holders, supporters and postgraduate students - current research discussed.
Year(s) Of Engagement Activity 2018
 
Description Adriano Rossi - invited speaker. University of Edinburgh. "Show and Tell" Meeting on Innate Immunity of the Brain and Body. Presentation entitled "Targeting myeloid cells to promote resolution of inflammation and tissue repair" on the 23rd April 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact University of Edinburgh. "Show and Tell" Meeting on Innate Immunity of the Brain and Body. Presentation entitled "Targeting myeloid cells to promote resolution of inflammation and tissue repair" on the 23rd April 2018

To foster new collaborations between inflammation and neuroscientists
Year(s) Of Engagement Activity 2018
 
Description Adriano Rossi invited speaker. France, Becason, Conference entitled '1st resolution Days: the resolution of inflammation, opportunities for innovative therapeutics' on April 4-6th 2018. Presentation entitled "Therapeutic strategies to enhance the resolution of inflammation to promote tissue repair and regeneration" on the 6th April 2018. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Attended by key scientists and their teams including post-graduate students
Year(s) Of Engagement Activity 2018
 
Description Adriano Rossi talk presentation. NC3rs London symposium. Talk entitled "Cellular and mechanistic processes linking inflammation and tissue repair: use of zebrafish larvae on the 23rd March 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Postgraduate students and NC3Rs grant holders and members of the NC3Rs attended
Year(s) Of Engagement Activity 2018
 
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 Cyto 2017 Boston, 32nd Congress of the International Society for Advancement of Cytometry, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Cyto 2017 Boston, 32nd Congress of the International Society for Advancement of Cytometry, Hynes Convention Center, Boston, Massachusetts, USA. ACEA Symposium. "Flow Cytometric Assessment, Quantification and Regulation of Human Neutrophil Extracellular Traps (NETs)". 12th June 2017
Year(s) Of Engagement Activity 2017
URL http://cytoconference.org/2017/Home.aspx
 
Description Eosinophil and Asthma 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Our publication (Duffin et al., 2009) entitled "The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1" resulted in a University press release that was selected for publication the in lay press (BBC website) and national newspapers (The Scotsman, Daily Express, Metro) released on the 10th Dec, 2009. Additionally Prof Rossi was intereviewed for a radio news bulletin. Radio Forth and Westsound Radio broadcast the article on the 10th Dec 2009.

This was a very recent event that has generated general public interest
Year(s) Of Engagement Activity 2009
 
Description European Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact European Congress of Immunology Location: Glasgow, SCOTLAND Date: SEP 05-08, 2012

Use of the human eosinophilic cell line EoL-1 to investigate the molecular mechanisms regulating cyclin-dependent kinase inhibitor drug-induced apoptosis
Author(s): Alessandri, AL, Hoodless, L , Lucas, CD, Lyons, JF, Haslett, C, Duffin, R, Rossi, AG
Source: IMMUNOLOGY Volume: 137 Special Issue: SI Supplement: 1 Pages: 261-261 Published: SEP 2012

This was a very well received poster with many delegates from the academic, industrial and research funding bodies showing interest.
Year(s) Of Engagement Activity 2012
 
Description FlowUK Edinburgh. Adriano Rossi - Organizer and Speaker in the Workshop on "Stem Cells in Focus". Presentation entitled "Stem cells in focus: an introduction" on the 19th July 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact FlowUK Edinburgh. Organizer and Speaker in the Workshop on "Stem Cells in Focus". Presentation entitled "Stem cells in focus: an introduction" on the 19th July 2018

National conference aimed at researchers and the flow cytometry community.
Year(s) Of Engagement Activity 2018
 
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 Invited speaker at Summer School, Leiden, Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Summer School, Leiden, Netherlands. 8-12 July 2019. Immune modulation in human and animal infection; impact on health, disease and therapy. Lecture on the 10th July 2019 entitled "Host-directed therapies and check point modulation in infectious disease".
Year(s) Of Engagement Activity 2019
 
Description MRC CIR website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The MRC Centre for Inflammation Research has a frequently updated web site where our research grants and publications are show-cased. Genral MRC CIR website: http://www.cir.med.ed.ac.uk/index.asp Prof Rossi's MRC CIR webpage: http://www.cir.med.ed.ac.uk/content.asp?sID=46&pID=46 Prof Haslett's MRC CIR webpage: http://www.cir.med.ed.ac.uk/content.asp?sID=46&pID=68

The MRC Centre for Inflammation Research and our own specific research results in frequent enquiries from potental researchers and the general public.
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
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 Magdalena Oremek presented (Adriano Rossi attended) - 31st May 2018, oral presentation: European Society for Clinical Investigation (ESCI) Phagocyte workshop. Presentation title: "Cellular and mechanistic processes linking inflammation and tissue repair" Magdalena was awarded travel grant 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact European Scientific Meeting
Year(s) Of Engagement Activity 2018
 
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 and Therapeutics in Edinburgh Website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact http://www.pte.ed.ac.uk/Home_files/Rossi.pdf This web site promotes our research and research outputs to the pharmacology and pharmaceutical community as well as to the general public

I have had potential future collaboration and prospective employees contact me through information gained from accessing this website
Year(s) Of Engagement Activity 2006,2007,2008,2009
URL http://www.pte.ed.ac.uk/Home_files/Rossi.pdf
 
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 Poster presentation by Magdalena Oremek - 24th-26th January 2019, Banff Inflammation Workshop 2019. Banff, Canada. Poster title: "Linking Inflammation and Tissue Repair using Zebrafish- the Role of the Inflammatory Cells" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International conference- Adriano Rossi invited as key note speaker - Magdalena attended as Adriano's trainee.
Year(s) Of Engagement Activity 2019
 
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 ¬ Madelena Oremek and Adriano Rossi- 23rd March 2018, Poster session: NC3Rs day- London. Poster title: "Cellular and mechanistic processes linking inflammation and tissue repair" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact ¬ 23rd March 2018, Poster session: NC3Rs day- London. Poster title: "Cellular and mechanistic processes linking inflammation and tissue repair"
Year(s) Of Engagement Activity 2018
 
Description ¬ Magdalena Oremek and Adriano Rossi. 24th May 2018, Poster session 3Rs day University of Edinburgh- Edinburgh. Poster title: "Cellular and mechanistic processes linking inflammation and tissue repair" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact For many post-graduate and under-graduate students and University teachers
Year(s) Of Engagement Activity 2018
 
Description ¬ Talk by Adriano Rossi - Heriot-Watt University, NC3Rs Symposium. Presentation entitled "Cellular and mechanistic processes linking inflammation and tissue repair: use of zebrafish larvae" Talk on the 14th May 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact Adriano Rossi gave a talk to individuals supported by grants from the NC3Rs and to members of the NC3Rs.
Year(s) Of Engagement Activity 2018