IISN-DC · Understanding the functional role of Immune-related Intercellular Signalling Networks during tissue Development and Cancer

Intercellular signalling networks drive tissue fundamental processes. Immune cells present a wide range of versatile functions and distinctive plasticity, which position them as tissue signalling-hubs during tissue development, homeostasis and cancer. Recent genomic advances have greatly improved our understanding of cell composition and states; however, investigation of the molecular signatures of intercellular crosstalk at the single-cell level remains limited. Exploring tissue development, homeostasis and cancer from the point of view of immune-controlled signalling networks, has the potential to reveal novel therapeutic candidates with high biological and medical impact. By applying functional assays alongside novel single-cell RNA-sequencing technologies and computational approaches, as physically interacting-cell sequencing (PIC-seq), I propose to crack the functional consequences of the whole-tissue signalling networks to revisit key developmental and cancer immunology questions:1) What immune-related intercellular crosstalk drives tissue development and cancer? We will integrate scRNA-seq and PIC-seq analysis along mouse lung, liver and kidney development, and human carcinomas, and apply large-scale comparative cross-tissue and cross-species analysis, ex-vivo and in-vivo studies, to identify tissue-exclusive and shared signalling during tissue physiology or cancer.2) What can we study on tumor-escape mechanisms, based on physiological signalling networks? We will perform development versus cancer large-scale molecular comparisons, in-vivo cancer models for functional perturbations, and clinical validations, to identify novel immunotherapy targets. Successful completion of the project will reveal novel cancer and developmental immunotherapy targets. Concomitantly, findings will comprise a valuable resource for tissue-molecular signalling and will generate a platform for investigating biological enigmas by elucidating consequences of cellular-communication.