CO-CREATE aims to reduce childhood obesity and its co-morbidities by working with adolescents, to create, inform and disseminate obesity-preventive evidence-based policies. The project applies a systems approach to provide a better understanding of how factors associated with obesity interact at various levels. The project focus on adolescence as the specific target group, a crucial age with increasing autonomy and the next generation of adults, parents and policymakers, and thus important agents for change. CO-CREATE involve and empower adolescents and youth organizations to foster a participatory process of identifying and formulating relevant policies, deliberating such options with other private and public actors, promoting relevant policy agenda and tools and strategies for implementation. CO-CREATE strengthen interdisciplinary research and have an inclusive multi-actor approach with involvement of academics, policy makers, civil society, relevant industry and market actors to ensure long-lasting implementation of the results. The project reflects and builds on a number of existing initiatives and platforms, including the extensive research activity from consortium members. The project has a strong gender profile and consider the relevance of geographic, socio-economic, behaviour and cultural factors. CO-CREATE engages international partners from different policy-contexts in Europe, Australia, South Africa and the US. Applying large-scale datasets, policy monitoring tools, novel analytical approaches and youth involvement will provide new efficient strategies, tools and programmes for promoting sustainable and healthy dietary behaviours and lifestyles. The generated knowledge and innovative tools for assessing actual policy implementation, strategies for empowering adolescents; and strategies for identifying, implementing and monitoring relevant policy programmes are applicable to stakeholders involved in the European efforts to tackle childhood obesity.

Chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma (HCC) are major challenges for global health. HCC is the second leading and fastest rising cause of cancer death worldwide. The limited availability of therapeutic options reflects our poor understanding of the molecular and clinical mechanisms involved in progression of liver disease. Chronic hepatitis C virus (HCV) infection is a main risk factor for HCC. Although HCC may be avoided by addressing the underlying cause in early stage disease, strategies to prevent HCC in patients with established cirrhosis and advanced fibrosis, in which the risk of HCC persists despite treatment of the underlying cause are lacking. Indeed, even HCV cure does not eliminate the risk of HCC development when advanced fibrosis is already present. Since fibrosis/cirrhosis-driven carcinogenesis is the mechanism of HCC development common to all major etiologies, we propose to use HCV-induced liver disease as a model to decipher the pan-etiology sequence of molecular events underlying disease progression and HCC. Our own data provide solid evidence that HCV infection alters pathways implicated in liver disease progression, including cirrhosis deterioration, HCC development, and overall and liver-specific death. Thus, the molecular investigation of these pathways will identify key cell circuits for the understanding of the pathogenesis of liver disease and HCC in general, and as broadly applicable pan-etiology diagnostic and therapeutic targets. Using a novel patient-derived cell culture model system for liver disease biology combined with advanced functional genomics, novel animal models and clinical investigation, we aim to uncover the cell circuits that are of clinical relevance for liver disease progression and cancer. By providing novel targets and biomarkers for liver disease and HCC prevention, this proposal will have a marked impact on the management and prognosis of patients with liver disease and HCC.

Advanced liver diseases such as cirrhosis and hepatocellular carcinoma (HCC) are major challenges for global health. HCC is the second leading and fastest rising cause of cancer death worldwide. Viral and metabolic liver disease are the main risk factors for HCC, which nearly always arises in advanced liver fibrosis. For metabolic liver disease approved therapies are absent. Cure or suppression of viral infection cannot eliminate the HCC risk in patients with advanced fibrosis. Despite significant progress, therapeutic options for established HCC are still limited in efficacy and safety. Importantly, patient survival in HCC is dependent on the underlying fibrotic liver disease which is not targeted by approved HCC therapies. Addressing these unmet medical needs, FIBCAN aims to identify urgently needed targets for prevention and treatment of fibrosis-driven liver cancer. A key focus of FIBCAN will be the investigation of Claudin-1 as a previously undiscovered target for prevention and treatment of fibrosis-driven HCC. Our own data obtained in patient-derived model systems and tissues provide solid evidence that Claudin-1 is implicated in liver fibrosis and hepatocarcinogenesis, and overall and liver-specific patient death. To discover novel targets, we will apply a liver disease discovery platform modeling the clinical cell circuits of cirrhotic patients progressing to HCC combined with single cell RNA-seq and spatial transcriptomics of patient tissues. Proof-of-concept studies of target-specific compounds combined with biomarker discovery in cutting-edge patient-derived model systems will deliver novel strategies for further clinical development. A strong collaboration with pharma will lead to rapid translation of the FIBCAN program into the clinic. By delivering urgently needed therapeutic strategies for advanced liver disease and HCC, this proposal will have a marked impact on the management and outcome of patients with advanced liver disease in Europe and beyond.