A key problem in Mental Health is that up to one third of patients suffering from major mental disorders develop resistance against drug therapy. However, patients showing early signs of treatment resistance (TR) do not receive adequate early intensive pharmacological treatment but instead they undergo a stepwise trial-and-error treatment approach. This situation originates from three major knowledge and translation gaps: i.) we lack effective methods to identify individuals at risk for TR early in the disease process, ii.) we lack effective, personalized treatment strategies grounded in insights into the biological basis of TR, and iii.) we lack efficient processes to translate scientific insights about TR into clinical practice, primary care and treatment guidelines. It is the central goal of PSYCH-STRATA to bridge these gaps and pave the way for a shift towards a treatment decision-making process tailored for the individual at risk for TR. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for TR across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression. PSYCH-STRATA will i.) dissect the biological basis of TR and establish criteria to enable early detection of individuals at risk for TR based on the integrated analysis of an unprecedented collection of genetic, biological, digital mental health, and clinical data. ii.) Moreover, we will determine effective treatment strategies of individuals at risk for TR early in the treatment process, based on pan-European clinical trials in SCZ, BD and MDD. These efforts will enable the establishment of novel multimodal machine learning models to predict TR risk and treatment response. Lastly, iii.) we will enable the translation of these findings into clinical practice by prototyping the integration of personalized treatment decision support and patient-oriented decision-making mental health boards.

Over 4 million hospital patients acquire a healthcare-associated infection (HAI) in the EU each year. Moreover, the global crisis of antimicrobial resistance means that HAI is posing an increasing cost and risk of mortality. There is clear evidence that airflow controls the dispersion and exposure to airborne pathogens and determines the contamination of critical surfaces in the human-centric climate (HCC), which is defined as the microenvironment which surrounds and is close to a human body. This points to a significant need for innovation in healthcare indoor environments to tackle the challenge of infection control, while improving thermal comfort and energy efficiency in hospitals. To achieve this, we must both advance the fundamental understanding of how people are exposed to airborne pathogens and develop new tools and techniques to enable effective design and operation of healthcare environments. Specifically, there is a need to understand better the local influence of airflows on particles in HCC; quantify the transient behaviour of airflows and contaminants due to healthcare activities like surgery; develop methods for optimising and adapting ventilation systems to control for risks in different environments like operation rooms and isolation rooms; and develop tools to enable real-time interaction with environments during design and operational phases. Bringing together 8 leading academic teams, 4 healthcare facilities and 8 HVAC industry partners, the HumanIC network aims to build a new approach to hospital environmental design through the concept of HCC and the training of 15 Early Career Stage Researchers to address these needs. HumanIC will create and disseminate fundamental and applied science to improve the knowledge base and innovate new technologies for designing and operating hospital ventilation and thermal systems and for reducing infection risk by at least 30%, meanwhile satisfying requirements of thermal comfort, safety and energy.

Pregnancy involves biological adaptations that are necessary for the onset, maintenance and regulation of maternal behavior. We were the first group to find (1, 2) that pregnancy is associated with consistent, pronounced and long-lasting reductions in cerebral gray matter (GM) volume in areas of the social-cognition network. The aim of BEMOTHER is to develop an integrative model of the adaptations for motherhood that occur during pregnancy and the postpartum period by: i) establishing when the brain of pregnant women begins to change and how it evolves; ii) characterizing the dynamics of cognitive performance, theory-of-mind, maternal-infant bonding and psychiatric measures; iii) assessing the effect of environmental and/or psychological factors in the maternal adaptations, iv) identifying the metabolomics biomarkers associated with maternal adaptations, and v) integrating the previous findings within the Research Domain Criteria framework (RDoC) (3). We will use a prospective longitudinal design at 5 time points (1 pre-pregnancy session, 2 intra-pregnancy sessions and 2 postpartum sessions) during which neuroimaging, psychological, behavioral and metabolomics data will be acquired in 3 groups of women: a group of nulliparous women who will be undergoing a full-term pregnancy, another group of nulliparous women whose same-sex partners will undergo a full-term pregnancy, and a group of control nulliparous women. We will provide the longitudinal RDoC-based model at the end of the study, but we will also deliver intermediate longitudinal evaluations after the postpartum session, as well as cross-sectional analyses after the first intra-pregnancy session and the postpartum session. BEMOTHER is timely and innovative. It adopts the translational RDoC framework in order to provide a pioneering, comprehensive and dynamic characterization of the adaptations for motherhood, addressing the interaction among different functional domains at different levels of analysis.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia affecting more than 6 million Europeans with a cost exceeding 1% of the EU health care system budget (13.5 billion annually). New treatment strategies and the progress achieved in research on AF mechanisms and substrate evaluation methods to date have not been commensurate with an equivalent development of the knowledge and technologies required to individually characterize each patient in search of the most efficient therapy. PersonalizeAF addresses this challenge by delivering an innovative multinational, multi-sectorial, and multidisciplinary research and training programme in new technologies and novel strategies for individualized characterization of AF substrate to and increase treatments’ efficiency. From the research point of view, PersonalizeAF will integrate data and knowledge from in-vitro, in silico, ex vivo and in vivo animal and human models to: 1) generate an individual description of the state of the atrial muscle identifying the disease mechanisms and characteristics; 2) understanding the potential effect that different therapies have on different atrial substrates; and 3) combining this information to generate a specific profile of the patient and the best therapy for each patient. With this purpose, PersonalizeAF partnership aggregates relevant scientific staff from the academic and clinical world with highly specialised biomedical companies which will be involved in a high-level personalised training programme that will train a new generation of highly skilled professionals and guarantee ESRs and future PhD students outstanding Career Opportunities in the biomedical engineering, cardiology services and medical devices sectors. PersonalizeAF will disseminate results to a wide spectrum of stakeholders, create awareness in the general public about atrial fibrillation and encourage vocational careers among young students.

Cell therapy based on regulatory T cells (Treg) transfer has acquired great interest for the treatment of autoimmune diseases, graft rejection or graft versus host disease (GVHD). Until now, this therapy has not rendered definitive clinical results in humans mainly due to the low number and limited quality of differentiated Treg purified from adult peripheral blood. To overcome these limitations, the host group has developed a new technology to produce massive amounts of GMP Treg derived from the thymic tissue (thyTreg), which are being employed in a clinical trial as an autologous cell therapy in transplanted children. However, the massive amount of thyTreg obtained from each thymus make possible to produce hundreds of doses that could be also employed allogenically to treat a range of immune diseases and patients. My experience and acquired skills in immunology will provide the host with the adequate knowledge to develop the allogenic use of thyTreg. The goal of my research will be to investigate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible its “off-the-self” use, and secondly to initiate a clinical trial to evaluate the safety/feasibility of a therapy with allogenic thyTreg in patients with GVHD. The project will establish the basis for the development of allogenic thyTreg cell therapies to suppress the harmful immune response underlying autoimmune diseases, transplant rejection, GvHD, and cytokine release syndrome associated with CAR-T therapy or clinical progress in COVID-19 patients. This innovative project will reinforce my expertise in immune disorders, gaining experience in translational research from the pre-clinical stages to the development of clinical trials and transfer of technology. Being part of this host institution participating in leading projects and international partnerships provides the ideal environment to complete my training and to develop my leadership abilities to become an independent researcher.