The overall goal of this project is to develop a radically new diagnostic and therapeutic device for neurological applications which combines a highly innovative ultrasound component for brain imaging and focused stimulation of brain regions with advanced electrophysiological measurements of neural activity. First goal of the project is the development of a novel ultrasound (US)-based functional imaging method that, in conjunction with electroencephalography (EEG), allows for high spatiotemporal resolution examination of brain activity. While EEG itself yields best data from neural tissue close to the skull, the US component is designed to deliver images from deeper brain regions. The second pillar of the devices function is focused US brain stimulation. Based on the possibility to localize abnormal activity, the neuromodulation component of the novel device can be guided to focal stimulation of selected brain regions, which can be further developed into a closed-loop design. The full envisioned system is a versatile tool that combines EEG-sensors and US transceivers in a wearable headset. The project foresees the development of hard- and software as well as algorithms to integrate the information from both modalities into functional neuroimaging with unpreceded spatiotemporal resolution. Beyond the technical realization, this project includes a proof of concept study to evaluate and demonstrate practical applicability in healthy participants and in patients with epilepsy, during clinical routine examination, cognitive, and sensory stimulation, including test-retest validation. The new device will reduce the time to examine and treat neurological patients and the cost thereof. The ability to perform better diagnosis via accurate imaging, targeted neurostimulation, and neuromodulation with a cost-effective, non-invasive device will have transformative effects on treatment options for neurological diseases and stimulate new lines of research in cognitive neuroscience

“BARRICADE” is about an evolutionary platform to predict breast cancer (BC) patients outcome and response to therapy in a faster and specific manner. Breast cancer is one of the leading causes of cancer mortality among women and is characterized by a high interindividual variability in response to cancer treatment, and often resistance to therapy arise over the time or after first line of treatment. For this reason, the therapeutic approach of each patient has to be set up during its management causing some gaps, useless toxicities and a losing of time useful for patient’s cure. In cancer research, cells are usually grown in a monolayer on dishes of polystyrene plastic to perform experiment or toxicity studies. Alternatively, researchers use animal models that are able to mimic a more physiological growth of tumor cells and they take in account also the microenvironmental influences. Unfortunately, animal models do not recapitulate the human complexity, and sometimes they do not predict tumor behaviour and clinical response. For this reason, organoids are emerging as new more complex system that may overcome the limitations of traditional cancer model. “BARRICADE” will contribute to taking BC cancer therapy to beyond state-of-art, developing personalized anticancer therapies and giving useful information for cure setting up. Indeed, progress in developing in vitro 3D organoid culture system using primary human breast cancer tissues have attracted great interest as an emerging tools for precision medicine. BARRICADE will help to overcome some of those barriers by giving preclinical information for future therapy settings.

In current society, a growing number of individuals is affected by mental disorders, thus representing a burden with significant health, social and economic consequences. Notwithstanding, the ethiology of mental disorders is still not fully understood, there is a growing evidence that current trend to delay first childbirth above age of 35 is a factor of risk for the onset of mental disorders (i.e. autism, schizophrenia) in resulting offspring. This “new” reproductive trend, caused by social and economic factors, has already allowed the birth of millions of babies worldwide. In the last decade, epidemiological studies have suggested that children conceived at advanced maternal age are at higher risk of autism spectrum disorders as well as psychotic and/or bipolar disorder and those conceived at advanced paternal age at higher risk of autism and schizophrenia. However, data from population-based investigation are often controversial, due to several confounding factors (i.e. health, socio-economic status, lifestyle), and information from animal studies are still limited. In this context, the assessment of neurological and/or psychiatric health of offspring conceived at advanced parental age (APA) is urgently needed. Moreover, understanding the mechanism(s) behind increased risk of mental affliction (i.e. autism and/or schizophrenia) will contribute to the identification of novel marker for neurologic/psychiatric disorders with a significant impact on basic science, society and health care services.“NeuroAPA” aims to identify structural and functional abnormalities in adult brain which may contribute to the increased risk of psychiatric disorders (i.e. autism, schizophrenia) in offspring conceived by parents at advanced parental age.

“Gl.EXO” is about innovative tools to detect Glioblastoma (GBM) exosomes and to have a timely, accurate and non-invasive diagnosis of GBM. Several studies have underlined the role of exosome cell–cell communication in different tumour types, including GBM, suggesting their potential use as diagnostic/prognostic/predictive biomarkers and therapeutic agents. In fact, evidences have demonstrated that the release of GBM exosomes plays a key role in cancer growth and progression by modulating tumor microenviroment and affecting angiogenesis, tumour migration, immune escape and drug resistance. However, GBM exosomes-enriched proteins characterization started only since few years and studies still lack informations on GBM exosomes cargo and their impact on cancer progression. Moreover, the identification of specific biomarkers able to discriminate between cancer exosomes from normal exosomes and tools for their detection are necessary and still unknown. Therefore, by inhibiting GBM exosomes uptake, “Gl.EXO” will contribute to hamper GBM progression in many cancer aspects. To address this issue, “Gl.EXO” aims to use nucleic acid-based aptamers as innovative tools to detect specifically GBM exosomes.