Research objectives

NGID will provide ultra-deep and ultra-high resolution dermatological data and identify biomarkers that elucidate pathophysiological mechanisms related to all six immune-dermatological diseases. Furthermore, high-potential biomarkers and mechanistic pathways will be further investigated and validated using translation human skin models where experimental insights will be gained on the skin (dys)function. Tailored to each specific disease and patient, this advanced understanding of immuno- dermatological pathophysiology for each of the six skin diseases makes NGID a ‘moonshot’ project with a far-reaching impact in other scientific fields including neurology, psychiatry, cancer and immunology in a broader sense. The uncovering of molecular mechanisms and main contributors leads to novel target discovery and drug screening strategies, i.e. our project will fuel drug development pipelines. It is therefore highly impactful for pharmacology.

NGID customizes promising, high-potential technologies for combined application on patient skin and dermatological biopsies. Obtained clinical data will be merged to provide a system-view on each individual patient, including: spatial mass cytometry, mass spectrometry imaging, spatial proteomics skin barrier lipidomics, metabolomics and various smart sensors for home monitoringIn addition, our technology platform contains tools that enable characterization of patient-reported outcomes, the classical physician-based clinical scoring, biophysical, cellular, microbiological, molecular biomarkers and the external factors. This combination of technologies has never before been applied to any single dermatological disorder. The disease-tailored combination of these techniques in a highly standardized trial setting provides a unprecedent high level of disease resolution. Moreover, throughout the project the technologies further developed towards remote and non-invasive application. Further application of these technologies has a significant impact in many research fields.

In NGID, for the first time sufficient high-resolution of the diseased tissue is available to identify suitable biomarkers for each of the disorders. The broad spectrum of the different diseases guarantees the discovery of novel discerning biomarkers for subtyping, disease monitoring and treatment. Moreover, the biomarkers will be validated using translational human models, and via continued data collection during and after the project. All these insights will ultimately lead to individual signatures for use in daily practice, constating of minimum set of robust biomarkers per disease. The individual signature of an individual patient can be directly linked to (complete) biomarker profiles in the NGID-infrastructure.

The NGID technology chain for analyzing native patient skin samples provides unprecedented abilities for deep-phenotyping translational skin models and for unraveling molecular disease mechanisms and drug target discovery. This wealth of data enables the refinement and development of state-of-the-art xeno-free human skin disease models based to grow organotypic skin tissue in the controlled laboratory environment. Currently our (basic) skin models are already being used by different industries (cosmetic, pharma, chemical and food) for research and drug screening purposes. They have voiced great interest in more sophisticated healthy and disease models (harboring e.g. endothelial cells, immune cells) for their drug development programs. The new developed models instigate a critical breakthrough in the field of translational human disease models. This work will become the showpiece for tailor-made, patient-centered healthcare, by guiding clinicians and patients towards rational, personalized therapies.

With NGID we will set the stage and break down barriers in implementation of alternatives in skin research, by offering data, high-end tools, technology, proof-of-concept and real-world evidence on utility/power of alternative models. NGID deep phenotyping and in-depth biomarker research will open a gateway to the refinement of human multi-cellular and immunocompetent models, with the ultimate goal to replace experimental animals in dermatological and in pre-clinical research and facilitate tailor made clinical trials based on solid in vitro data. This outlook fits perfectly with the mission of the Dutch government to become a true worldwide leader in animal-free innovations by 2025 and will build upon current funding to stream line the development of human skin models in The Netherlands.

In NGID high-level scientific evidence on psychological factors is obtained as part of prospective, randomized controlled clinical trials. This prospective and integrated – holistic - biopsychosocial approach is unique in psychology and dermatology, and urgently needed to bring the psychodermatological field forward. Moreover, improved understanding of underlying pathophysiological mechanisms also greatly contributes to gaining new insights into psychological factors. Combined, it provides guidance for clinical decision-making regarding the best multidisciplinary treatment trajectory for individual patient profiles. Our revolutionary progress in psychodermatology is of great interest to research fields in health and medical psychology and dermatology, that can use our research to optimize psychological and dermatological treatment guidelines and protocols regarding the involvement and influence of psychological factors in disease- and treatment outcomes.

NGIDs’ novel holistic “systems dermatology” approach will integrate all data sets in order to characterize the pathophysiology of each disorder in full detail. Using novel data science methods, NGID will yield a fully integrated, multi-parametric data set. Subsequently, our innovative machine learning approach makes it possible to connect data points and fully exploit the data. Newest molecular biology techniques including next generation (long read) sequencing, epi-genomics, spatial biology techniques, multi-omics and newest imaging technology are at our disposal. NGID also creates a new and unique nation-wide infrastructure for central data storage. With this “smart” repository we will enable continued data collection and data reuse for future research questions. Our combination of techniques, a dense complementary network of scientists and clinicians, as well as patients, will revolutionize patient care. Prediction of treatment response, side effects likeliness and disease control duration will be possible. Additionally our approach will enable ultra-high resolution unravelling of diseases and potentially novel targets that will foster drug discovery and drug development in the next decennium.

The centralised data hub services serve as golden standard and blueprint for other diseases such as skin cancers. Importantly, expansion to other therapeutic areas as neurology, gynaecology, psychiatry will be possible. Furthermore, internationalization will foster expansion potential in adjacent countries. All on the basis of technology, new research techniques and standardized sampling with a centralized, integrative nation-wide approach.