Final Action Meeting Eilat, Israel in November 2016 Action BM1203 - PowerPoint PPT Presentation

Final Action Meeting Eilat, Israel in November 2016 Action BM1203 (EU-ROS) Chair Prof. Andreas Daiber COST Domain - Biomedicine and Molecular Biosciences (BMBS)

Mission of COST The COST program (European Cooperation in Science and Technology) is one of the oldest funding instruments of the EU with the following aims:  Strengthen the collaboration among European scientists  Support early stage researchers  Improve European economics & health of European population 2

Facts of COST Action BM1203  Foundation in Dec 2012 (kick-off Meeting Brussels), first budget in April 2013  Chair of the Action: Prof. Andreas Daiber, University Medical Center Mainz, Germany  Vice Chair of the Action: Prof. Fabio di Lisa, Università di Padova, Italy  Founding Chair of the Action: Prof. Harald Schmidt, University of Maastricht, The Netherlands  34 participating countries, 2 NNC  101 MC members/substitutes and > 150 WG members (w/o ESR, STSM candidates, invited experts) 3

Scientific scope Major Scientific Aims  Unravel the paradox of diverging efficacy of antioxidants in clinical therapy (chronic / systemic versus acute / local applications)  Discriminate ROS sources and signalling in physiological pathways from disease-relevant processes  Overcome conservative dogma in oxidative stress and redox biology research and provide the room for new hypotheses and verify these concepts by state-of-the-art drugs, tools and imaging techniques  Develop new drugs with antioxidant properties (direct or indirect) for the treatment of oxidative stress-associated disease  Establish databases for drugs & tools as well as oxidative stress- related biomarkers to advance the European research in this field and to provide the basis for new therapeutics and large clinical trials  Establish long-lasting collaborations and support successful applications for funding by EU-ROS consortia 4

Scientific scope Scientific Working Groups Update on major achievements during WG sessions  Working Group 1 – Sources of ROS (Prof. Ulla Knaus)  Working Group 2 – Molecular Mechanisms (Prof. Agnes Görlach)  Working Group 3 – Drugs & Tools (Dr. Tamara Seredenina)  Working Group 4 – Biomarkers (Prof. Pietro Ghezzi)  Working Group 5 – Imaging (Dr. Yves Frappart)  Working Group 6 – Technology Transfer & Funding (Dr. Vincent Jaquet)  Within WG1&2 different consortia working on cardiovascular & neurodegenerative disease, cancer, fibrosis and inflammation 5

Scientific scope ROS sources ROS Beneficial redox signaling Detrimental in disease A, B, C targets Should be preserved by redox Should be specifically inhibited drugs in disease A, B, C Possible strategies: Repair of damaged proteins (e.g. sGC, eNOS), source specific inhibitors (Nox, XO inhibitors), activators of endogenous antioxidant systems (Nrf2 activators), inhibition of toxifiers (MPO), direct RONS scavengers only cell- or organelle-specific, maybe also species-specific Requires advanced imaging techniques to verify successful inhibition and specific biomarkers to verify successful therapy of disease phenotype y y y 6 Casas et al. or Schmidt et al., Antioxid. Redox Signal . 2015

Scientific Scope Who’s the bad guy – or which biological source of ROS formation is the most detrimental one? 7 Daiber, Di Lisa et al. Br. J. Pharmacol. 2015

Scientific scope Interaction (“crosstalk”) of different ROS sources 8 Modified from Daiber, Biochim. Biophys. Acta 2010

Scientific scope Redox regulation of disease-relevant enzymes 9 Schulz et al. and Daiber, Antioxid. Redox Signal . 2014

Scientific scope New antioxidant drugs 10 Vi Dao et al. Antioxid. Redox Signal. 2015

Scientific scope In vivo RONS imaging 11 Maulucci et al. Antioxid. Redox Signal. 2016

Scientific scope Redox biomarkers 12 Frijhoff et al. Antioxid. Redox Signal. 2015

Scientific outputs related to networking Collaborative research meetings  5 MC/WG meetings completed (Budapest, Istanbul, Padova, Munich, Bukarest), 4 WG meetings completed (Athens, Madrid, Belgrade, Lisbon), 3 SFRRe congress symposia completed (Athens 2013, Stuttgart 2015, Budapest 2016), final meeting in Eilat, Israel (Nov 2016)  29 STSM completed (Total payments: 42,488 EUR) – update by Jaime Kapitulnik in the STSM award session  2 co-organized training schools in 2013 (Zurich by Vincent Jaquet, Birmingham by Corinne Spickett), 1 co-organized TS in 2014 (Spetses), 1 COST-organized TS in 2015 (Alicante), 2 co- organized TS in 2016 (Portorož by Irina, Spetses) – all together more than 70 trainees and 22 trainers were supported 13

Scientific outputs related to networking Collaborative research meetings Kick-off Meeting Brussels 05 December 2012 LO: COST Office Management Committee & Workgroup Meeting Budapest 23-25 May 2013 LO: Peter Ferdinandy Workgroup Meeting Athens 23-25 September 2013 LO: Niki Chondrogianni Workgroup Meeting Madrid 9-11 December 2013 LO: Manuela Garcia Lopez Management Committee & Workgroup Meeting Istanbul 5-8 March 2015 LO: Suha Yalçın MC/WG/CG Meeting Padova, Italy 4-7 November 2014 14 LO: Fabio Di Lisa

Scientific outputs related to networking Collaborative research meetings 15

Scientific outputs related to networking Spetses training school 2014 – 18 students, 4 trainers LO: Consuelo Borras, Niki Chondrogianni 16

Scientific outputs related to networking Alicante training school 2015 – 36 students, 12 trainers LO: Antonio Cuadrado, Manuela García López 17

Scientific outputs related to networking Spetses training school 2016 – 12 students, 4 trainers LO: Lars-Oliver Klotz, Niki Chondrogianni 18

Scientific outputs related to networking Joint publications  Special, ROS/antioxidants-dedicated Forum Issue on “Redox Medicine” was published in Antioxidants & Redox Signaling 2015 with 10 contributions (Eds. Harald Schmidt, Fabio Di Lisa)  Virtual issue on “Emerging concepts in redox biology and oxidative stress” was published in Redox Biology 2016 with 18 contributions (Eds. Santiago Lamas, Fabio Di Lisa, Andreas Daiber)  Themed review series on “Redox biology and oxidative stress in health and disease” mostly published in British Journal Pharmacology 2016 with 16 contributions (Eds. Peter Ferdinandy, Andreas Daiber)  Final Action Dissemination on “Involvement of reactive oxygen species in physiology and pathophysiology – outcome and position statements of COST Action BM1203 (EU-ROS)” with up to 170 authors and 9 section editors from EU-ROS to be published in Redox Biology 2017  Plus more than 30 additional joint publications of WG members of EU- ROS 19

Scientific outputs related to networking Forum issue in Antioxidants & Redox Signaling 2015 5 of the review articles were in the top 10 of most read articles during the last 12 months from publication 20

Scientific outputs related to networking Virtual issue in Redox Biology 2015/2016 At least 5 of the review articles were in the top 25 of most read articles during the last 90 days from publication 21

Scientific outputs related to networking Themed review series in British Journal Pharmacology on “ Redox biology and oxidative stress in health and disease ” (Peter Ferdinandy, Andreas Daiber ) with the following published or submitted work from EU-ROS: Author teams Status Manuscript Title Notes Fabio Di Lisa, Rainer Schulz, Peter FerdAccepted and Exported New aspects on P66Shc in ischemia/reperfusion injury and protection from it Andreas Daiber, Huige Li, Santiago Lam Accepted and Exported Targeting endothelial dysfunction Gabriella Aviello, Ulla Knaus, … Accepted and Exported Gastrointestinal Inflammation and ROS (Crohn's, ulcerative colitis, ileitis...) Serge Bottari, Neven Zarkovic, Olha Yel Accepted and Exported Biomarkers of oxidative and nitro‐oxidative stress Andreas Daiber, Fabio Di Lisa, MatthiaAccepted and Exported Effects of the crosstalk of mitochondria with NADPH oxidase on endothelial dysfunction and vascular inflammatio Huige Li et al. Accepted and Exported Antioxidant effects of resveratrol in the cardiovascular system Jeanette Marjorie Wood et al. Accepted and Exported Therapeutic potential of NOX1/4 inhibitors Gethin J. McBean, Javier Egea, Manuel Accepted and Exported Redox‐based therapeutics in neurodegenerative disease Jankovic A, Korac A, Buzadzic B, Stancic Accepted and Exported Targeting the nitric oxide/superoxide ratio in adipose tissue ‐ relevance in obesity and diabetes management Pavel Urbanek and Lars‐Oliver Klotz Accepted and Exported Posttranscriptional regulation of FoxO formation Frederik Vilhardt et al Accepted and Exported NADPH oxidases in Microglia oxidant production: Activating Receptors, Pharmacology, and Association with Disea Frederik Vilhardt et al Accepted and Exported Microglia Antioxidants and Redox signaling Sebastian Steven et al. Accepted and Exported Glucagon‐like peptide‐1 receptor signalling reduces microvascular thrombosis, nitrosative and oxidative stress, … Piero Ghezzi, Vincent Jaquet, Fabrizio Accepted and Exported The oxidative stress theory: Demystifying the evidence for reactive oxygen species in physiology and disease Görlach A, Dulak J, Kietzmann T, Poelli Accepted and Exported Epigenetics and redox stress Ioanna Andreadou, Peter Ferdinandy Accepted and Exported Effect of hyperlipidemai on the heart: importance of oxidative stress 22