Organ-specific origins, regulation and functions of lymphatic vessels in development and disease

Lymphatic vessels within different organs have diverse developmental origins and exhibit remarkable tissue-specific specialisation.

We hypothesise that uncovering organ-specific features and functions of the highly ‘heterogenous’ lymphatic system will be of key importance for understanding the physiological and pathological roles of lymphatic vessels, and for developing therapies aimed at regulating (specific) vessel functions.

Towards this aim, we will define the organ-specific features and regulation of lymphatic vessels in three organs: the skin, lung and gut, using state-of-the-art molecular, cellular and genetic in vivo methods.

Building on our discovery of a previously unknown progenitor cell type that is required for lymphatic development in an organ-specific manner, we also set out to identify their origin(s) using genetic lineage tracing.

Transcriptomes of organ-specific lymphatic endothelial cells and progenitors will be determined by single cell RNA sequencing, and selected signature genes will be functionally characterised using genetic mouse models.

We will further investigate mechanisms underlying organ- and vessel-type specific disease manifestation caused by perturbations in the PI3K signaling using our new mouse model of vascular malformation.

This project will generate novel understanding of organ-specific regulation of the lymphatic vasculature and provide new insights into common human diseases associated with impaired lymphatic function.