Despite extensive self-organization abilities, the mucosal epithelial homeostasis is maintained by the local microenvironment, defined by spatio-temporal interactions between epithelium and stroma alike. Perturbations in the microenvironment caused by various extrinsic and intrinsic factors can result in malfunctioning interactions and are an underlying cause of many diseases, including cancers. To study the process of disease development, we have developed the 3D-organoid models of columnar and stratified epithelium from uterine endo-ectocervix and gastro-oesophageal epithelium from healthy, precancer, and cancer tissues. These mini-organs recapitulate the parent tissues, their lineage properties, and the factors that regulate their maintenance in vivo. The organoids can be expanded and cultured long-term and are amenable to genetic manipulations. We apply these models and further develop complex co-culture systems for our investigations for studying infections, disease development and mimic the dynamics of the tissue microenvironment in health and disease. 

Tissue homeostasis depends on cellular states and coordinated action of a spatially defined heterogeneous set of cells. Central to our research question is to understand the spatial expression, the origin of signals, timing, and gene expression level in the tissue or organ to elucidate molecular trajectories and identify key regulatory events during health, infection, and disease development. Towards this, we apply single-cell RNA sequencing approaches and spatial transcriptomics that enable us to define the transcriptomic landscape at single-cell resolution and visualize their spatial and morphological context.

We use sophisticated diet based and transgenic mouse models to investigate metaplasia development and the microbial interaction. Lineage tracing, a most widely used technique, provides a powerful means to identify the location and track the proliferation, migration, and differentiation of specific cell populations in vivo. It enables understanding tissue development, homeostasis, and disease. We apply lineage tracing in combination with fluorescent reporters and specific inducible promoters and advanced microscopy to identify and track specific cell populations in time-resolved experiments.