Aortic valve diseases are degenerative conditions that develop progressively and insidiously. Once symptoms become evident, life expectancy is significantly reduced. While treatments for these pathologies are widely available, there remains a remarkably high rate of procedural complications. These complications have been shown to have a negative impact on cardiac mortality and the likelihood of rehospitalization for heart failure. This underscores the need for further technological advancements. Protego's objective is to determine whether a combination of immunological and biomechanical profiles in patients with aortic valve diseases can effectively predict post-treatment prognosis. My goal is to develop an innovative, validated, and clinically applicable methodology that can identify the best treatment options and predict post-procedural outcomes while minimizing complications. This methodology will serve to determine the timing of treatment for patients with valvular aortic diseases and assess whether the proposed treatment is likely to be beneficial preoperatively, while also minimizing the risk of post-procedural complications. I will achieve this by combining imaging analysis, deep learning algorithms, in silico models, and in vitro tests. My approach involves the following key objectives: (i) creating a multi-physics digital twin of patients with aortic valve diseases, (ii) developing a validated, high-fidelity model for treatment with quantification of post-treatment outcomes and (iii) generating a proof of concept for a clinically applicable predictive model trained using both immunological profiles and biomechanical features of patients. This innovative approach will provide a deeper understanding of how clinical and biomechanical outcomes correlate with the amplification of inflammation, helping us comprehend the interaction between biomarkers and negative post-treatment prognosis in patients with aortic valve diseases.

In the European Union, cancer is the leading cause of death and the overall cancer incidence is still increasing. As a result of expanding efforts to improve cancer outcome, a main paradigm change is occurring in cancer therapy towards individualized medicine. Antibody-based therapies form an integral and constantly growing part of this approach. Antibody-based therapies will strongly influence the coming decade of cancer care. The importance of immunotherapy has been highlighted by the prestigious Science journal as “breakthrough of the year 2013”, heralding the rising importance of immunotherapy. Accordingly the need for well-trained and skilled researchers in academia and industry is dramatically increasing in this field. IMMUTRAIN is a training network bringing together experts in the fields of monoclonal antibodies, dendritic cells, T-cells and immunomodulatory nucleic acids with a considerable industrial involvement. The network comprises nine academic research groups and five industrial partners in a total of seven European countries. IMMUTRAIN will actively create synergies between those sectors by forming and promoting young researchers to match the challenges of immunotherapies. Particular focus will be placed on combinatorial therapies and on the new emerging field of bispecific antibodies used to target both the tumor and the patient´s immune system. Fifteen Ph. D. students (early stage researchers, ESR) reinforced by the project leaders will investigate innovative therapeutic strategies and provide the rationale for future clinical trials. Throughout their projects, ESR will learn to integrate academic and industrial aspects and will sharpen their experimental and complementary skills in a well-designed and diversified training program.

Algae4IBD's mission is to develop commercial products for Inflammatory Bowel Disease (IBD) prevention and treatment using aquatic natural biological resources. With the emerging developments in natural product, notable success has been achieved in discovering natural products and their synthetic structural analogues with anti-inflammatory activity. However, global biodiversity remains a largely unexploited resource for natural bioactive molecules with an enormous potential for developing commercial products with public health benefits. Micro and macroalgae, found in marine and freshwater, have been identified as promising sources of bioactive compounds including small molecules and secondary metabolites with a wide range of bioactivities as an antioxidant, anti-inflammatory and cancer preventive. Consumption of algae could, therefore, provide defence against chronic inflammatory diseases such as IBD, that until date have no effective cure. This project offers nature to bedside approach, using an entire development along the value chain for a new biodiscovery therapeutic approach by developing and examining algae-based compounds for IBD patients while guaranteeing algae's biodiversity preservation. We propose innovative solutions for increasing the use of algae-based ingredients and to ensure the science-based improvement of nutritional quality and its effect on public health. The researchers, companies and hospitals involved in the different stages of the project will use the biodiversity of algae, both micro and macro, as a wide source for bioactive compounds using state-of-the-art cultivation and extraction technologies for obtaining sufficient amounts of the bio-active molecules together with novel processing protocols. It will result in novel algal-based, high-quality bioactive compounds at GMP grade and lower costs for dual purposes – IBD prevention and treatment in relevance to the food as well as the pharmaceutical industries.

Mural cells (pericytes and vascular smooth muscle) enclose blood vessels and are critical for vascular homeostasis. Absence or malfunction of pericytes or vascular smooth muscle results in aneurysm formation in small or large blood vessels, respectively. Our previous work showed Tbx18 is selectively expressed in mural cells of multiple adult organs. Preliminary data indicates that, in mice, ablation of Tbx18 in mural cells results in aortic tortuosity and lethality due to rupture. These observations led to the hypothesis that transcriptional regulation by TBX18 in mural cells is critical for the development of functional vascular networks. To fully understand the roles of TBX18 in mural cells and eventually place it as a gene involved in human vascular disease, we propose to: 1) fully characterize the vascular phenotypes of Pdgfrb- Cre;Tbx18 mutants; 2) identify genes directly regulated by Tbx18 in mural cells; and 3) test a putative involvement of TBX18 in human aneurysmal diseases.

MEFISTO will develop two novel solutions to treat meniscus loss as a strategy for preventing the onset of an epidemic of post-meniscectomy knee osteoarthritis (OA) in Europe. Morphological profiling will identify the population of patients who, after meniscal resection, are at higher risk of early compartment degeneration, providing a personalized approach for the patient. The two different reconstructive strategies are: i) a controlled vascularized bioactive biodegradable meniscal scaffold, which will regenerate the native meniscus. This strategy will address younger patients with early osteoarthritic changes. ii) a bioactive non-biodegradable meniscal prosthesis, which will act as a mechanical unloading device and a drug delivery system, with the capacity to modulate the inflammatory environment. This strategy will address patients with advanced OA. A socio-economic analysis of the efficacy of existing meniscal substitutes will complete the project. This analysis is of vital importance for the European healthcare system, as it will provide a clear understanding of the costs and benefits of current clinical practice and predict the impact of the two new interventions. The technological innovation lies in the development of biologically active functionalized nanobiomaterials that can interact with the surrounding articular tissues. The biodegradable scaffold will promote revascularization in the peripheral zone, while leaving the inner zone avascular, reflecting the native meniscal tissue and functionalization with drug delivery micro/nanoparticles of the non-biodegradable device will provide modulation of inflammation. The impact is expected to be significant as so many patients have undergone or will undergo meniscectomy. The interventions developed in MEFISTO will prevent these patients from receiving joint-sacrificing procedures such as metal prosthesis whilst reducing the social burden, associated costs and high levels of morbidity resulting from OA.