Endocrine disruptors (EDs) are defined as exogenous chemicals that alter functions of the endocrine system, thereby causing adverse health effects in an organism or its progeny. Historically, the field of ED research has focused on reproductive endocrinology and related hormones, which is reflected in the regulatory test methods assessing endocrine effects of xenobiotics. However, recent evidence links increased incidence of metabolic syndrome (a cluster of metabolic risk factors including abdominal obesity, dyslipidemia, elevated blood pressure, and elevated fasting glucose) to EDs, increasing the incidence of atherosclerosis and type 2 diabetes. Despite these findings, adequate testing methods for metabolic effects of EDs are lacking. The project “Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways” (EDCMET) brings together experts in various research fields, including systems toxicologists, experimental biologists with a thorough understanding of the molecular mechanisms of metabolic disease and comprehensive in vitro and in vivo methodological skills and ultimately, epidemiologists linking environmental exposure to adverse metabolic outcomes. This proposal focuses on developing novel test methods and models to assess the metabolic effects of EDs. Combined in silico methods, in vitro and in vivo methods are developed with an emphasis on liver and adipose tissue and endocrine pathways related to their metabolism. In addition, epidemiological and field monitoring data is used to gain information regarding the exposure to chemicals and ED-related metabolic effects. The interdisciplinary approach and complementary expertise of the participants will identify novel mechanisms of action, and in collaboration with the European Commission Joint Research Centre (JRC) providing an interface between the programme and European regulatory agencies, novel validated test methods for regulatory purposes will be generated.

Medicine today experiences a gap between basic research and successful clinical translation that delays establishment of urgently needed therapies. This is very clearly so in blinding retinal degenerations (RDs), where most are yet untreatable, even with a wealth of basic and pre-clinical research data available. To address this problem, transMed proposes an innovative programme to educate “translational researchers” that focuses on the bench-to-bedside development of treatments for RD. The transMed consortium joins four academic groups (EKUT, UNIMORE, ULUND, HI) with four non-academic and SME partners (SPPD, INCU, Oculis, PamGene), and five partner organisations (2BBB, BIOLOG, NLO, HCTC, EVI) with intersectoral collaborations already ongoing. Each transMed partner will contribute specific critical expertise to a curriculum covering all major aspects of translational research: From basic research into disease mechanisms and target definition, to drug design and development, in vitro test systems and in vivo disease models, drug delivery systems, biomarkers, good manufacturing practice, toxicological testing and pharmacokinetics, regulatory affairs, intellectual property, all the way to clinical trials and commercialisation. transMed builds on and integrates three relevant translational projects, which are at the early pre-clinical, late pre-clinical, and early clinical stages, respectively, to provide the project’s Early Stage Researchers with the broadest possible overview. The training is completed by e-lectures, the inclusion of dedicated conferences for young researchers, a secondment and hands-on course programme from industry to academia and vice versa, permitting further insight and networking in the European biotech industry. Altogether, transMed will offer its students the opportunity to obtain a competitive PhD degree in several critical areas of biomedical research, providing for a strong employability in both the private and public sector.

Cancer is the second leading cause of death worldwide, accounting for 10M deaths in 2020. Although 7 Immune Checkpoint Inhibitors (ICI) are approved for different cancer indications and have represented a true breakthrough, only 10-50% of advanced cancer patients respond to the treatment. This unpredictability of results, together with 15-60% severe toxicity rates and high prices are restricting the impact potential of ICIs. Predicting ICI response is critical for fully realizing their potential in treating early-stage tumours and enhancing ICI treatment regimens. PamGene’s IOpener is a ground-breaking in vitro diagnostics testing platform for ICI response prediction. Made possible by PamGene’s proprietary microarray-based kinase activity profiling of host immune cells, it can predict a patient’s response before ICI therapy is started from a simple blood draw. The IOpener aims to revolutionize the precision-medicine sector, enabling the widespread use of ICIs at any cancer stage.

Uveal melanoma (UM) is a rare intraocular tumour with an incidence of 5 cases per million individuals per year. Up to 50% of UM patients develop metastases, most often in the liver, and these are invariably fatal. Despite new discoveries in the genetic and molecular background of the primary tumour, little is known about the metastatic disease; furthermore, there is no therapy to either prevent or treat UM metastases. In UM Cure 2020, we aim to identify and validate at the preclinical level novel therapeutic approaches for the treatment of UM metastases. For this purpose, the consortium brings together the major experts of UM in both patient care and basic/translational/clinical research, as well as patient representatives. An ambitious multidisciplinary approach is proposed to move from patient tissue characterisation to preclinical evaluation of single or combinations of drugs. This approach includes the characterisation of the genetic landscape of metastatic UM and its microenvironment, proteomic studies to address signal pathway deregulation and establishment of novel relevant in vitro and in vivo UM models. We also aim to validate accurate surrogate endpoint biomarkers to evaluate therapies and detect metastases as early as possible. Underpinning this will be the UM Cure 2020 virtual biobank registry, linking existing biobanks into a harmonised network, which will prospectively collect primary and metastatic UM samples. Together, our approach will lead to the identification of new therapies, allowing the initiation of UM-dedicated clinical trials sponsored by academia or pharma. Dissemination of results will include the building of a patient network across the countries as part of the consortium as well as a dedicated UM patient and caregiver’s data portal as part of the UM Cure 2020 website, in order to increase patient information and disease awareness.