Final Report Summary - IT-LIVER (STRATEGY TO INHIBIT TGF-Beta IN LIVER DISEASE) The IT-LIVER consortium included 10 partners, 8 representing research in academia and 2 the industry application domains. The project partners are from Spain, the Netherlands, Sweden, Germany, Austria and Italy. A further 2 organizations representing industry participated as associated partners. The Initial Training Network (ITN) was coordinated by Dr. Isabel Fabregat at IDIBELL, Barcelona, Spain. A public website for IT-LIVER was created: www.it-liver.eu and was continually updated reflecting the latest network training events and publications. A broad spectrum of scientific and technological capacities is needed to accomplish the goal of discovering drugs and treatment modalities for chronic liver diseases (CLD) and hepatocellular carcinoma (HCC). Following bilateral interactions, IT-LIVER partners - in academia and industry alike: http://www.it-liver.eu/#participants - concluded that the solution was to create a European network that brought together in an integrative way the expertise to provide a comprehensive research and training programme with the goal to combat CLD by:i) Unraveling the molecular and cellular complexities of the Transforming Growth Factor –beta (TGF-beta) responses in CLD progression, andii) Rationally designing and discovering CLD drugs, drug delivery systems and CLD treatment modalities, based on targeting the TGF-beta pathway.Consequently, this ITN formulated the mission to provide a multidisciplinary and intersectorial TRAINING PROGRAMME for talented young researchers (early stage –ESR- and experienced –ER- researchers), so as to prepare them for leading roles in CLD research and drug discovery in European industry and academia.The specific AIMS of the ITN programme were:• To provide a research training programme aimed at acquisition of : i) “state of the art” knowledge of the skills spectrum needed to better understand CLD, i.e. science and technologies of basic molecular liver cell biology, drug discovery and delivery systems, development of preclinical models and preclinical treatment modalities; ii) the ability to assimilate the individual components of the skills spectrum such that they will be able to oversee in a goal-oriented manner the multisectorial process of combating diseases in general, but CLD in particular.• To increase employability of the ESR/ERs in the higher ranks of academia and industry by enhancing their transferable skills in writing and communication and intellectual property management, valorization, entrepreneurship, etc.• To strengthen intersectorial research cooperation to advance our understanding of the molecular and cellular mechanisms of CLD progression and to translate this knowledge into drug discovery and treatment modalities.To achieve these objectives, we organized different activities:i) A total of 15 fellows (http://www.it-liver.eu/IT-Liver/fellows.html) were incorporated at some point during the 4 years of the project. They were involved in a multidisciplinary research programme for the study of TGF-beta in CLD that was subdivided in 2 subprogrammes: a) Molecular mechanisms; b) Target discovery and preclinical models. Detailed projects are described at: http://www.it-liver.eu/IT-Liver/project-list.html.ii) Different events were organized (5 workshops and a final conference, as well as fellows’ secondments in other partner’s laboratories, with particular emphasis in movement from academy to industry and vice versa) which have provided specific and complementary training in skills essential for giving the ESR/ER a competitive edge. The consortium established a Supervisory Board in which all the partners, three elected representatives from the ESR/ERs and four external representatives participated. The external participants were well recognized experts in the field. Visit http://www.it-liver.eu/IT-Liver/itn-training.html for more details. A relevant consequence of these direct interactions is the number of strong collaborations that have been initiated among the different partners (academy and industry) involved in the proposal. This has resulted in numerous presentations of results in scientific meetings and published papers where two or more partners were involved. The action has significantly increased the scientific potential of all the partners and their capacity to compete with the best groups in this field. This action has allowed the creation of a scientific European network that will remain active after the ITN.The ITN has allowed a significant progression in the professional careers of the fellows incorporated. Various ESRs have defended the thesis and others will defend it in the next months. Some of the fellows continue hired in the company/institute, either permanently, or temporary to finish their works. Finally, we are proud to say that some of the fellows, after finishing the IT-LIVER contract, got excellent jobs coming back to their original countries.Results have contributed to:i) Better understanding the intracellular signaling of the TGF-beta family of regulatory peptides and its relevance in liver pathologies. Collaboration among the different partners has opened to the fellows the use of innovative technologies, such as throughput “omic” analyses.ii) Deepening the relevance of the TGF-beta pathway in liver fibrosis and hepatocarcinogenesis to better design targeted therapeutic tools, through the use of novel in vitro and in vivo models.iii) Testing new strategies for inhibiting the TGF-beta signaling, as well as innovative delivery techniques. iv) Identifying new TGF-beta related biomarkers that will help to select those patients most likely to benefit from therapy aimed at inhibiting the TGF-beta pathway.The scientific and economic impact of the results is very high, due to the lack of efficient therapeutic tools in CLD, in particular in HCC. For these reasons, the original results are being published in excellent journals in the area of research (for details go to: http://www.it-liver.eu/IT-Liver/original-publications.html) and collaborative review articles have been also published (http://www.it-liver.eu/IT-Liver/review-articles.html).The ITN has also contributed to disseminate the problematic of CLD to the society. Different events have contributed to this: divulgatory talks, as well as press notes and specific acts to show how the IT-LIVER action is working for finding new therapeutic drugs in liver fibrosis and cancer. One of the most relevant actions in this context was the video that was recorded at the beginning of the action and that has been presented in all of the dissemination acts, workshops and conferences where IT-LIVER has participated. The video can be viewed online at: http://www.it-liver.eu/ and on YouTube. Facebook and Twitter have also contributed to IT-LIVER dissemination.
