Defining cell “citizenship” during organ growth and regeneration

Over the past years my lab has used the zebrafish model to address the molecular and cellular underpinnings of blood and lymphatic vessel formation, and the instructive role the vasculature plays during embryonic development, organogenesis, and regeneration. Our discoveries have greatly contributed to the current understanding of the origins, specification, and sprouting of lymphatic endothelial cells (LECs) in the developing embryo, as well as to the emerging link between circulating lipoproteins and EC behavior. In recent years we expanded our focus to include the physiology and pathophysiology of the vascular system during organ growth and regeneration. Although it is largely accepted that the vessels of each organ display specific features that enable them to fulfill specialized functions, the mechanisms regulating the formation of organ-specific vessels are not fully understood. Our latest studies have already begun to uncover exciting new roles for vessels of different organs. For instance, we discovered the existence of different types of lymphatic vessels in the zebrafish and mouse hearts that behave differently in response to injury, and contribute differentially to heart regeneration (Gancz et.al., eLife, 2019). In addition, our most recent study analyzing the formation of the zebrafish fin vasculature identified for the first time a new innate mechanism of blood vessel formation through LEC transdifferentiation, and provided in vivo evidence for a link between EC ontogeny and functionality (Das et.al., Nature, 2022).

Currently, we are characterizing new endothelial cell types present in organs with marked hematopoietic/immune functions, with particular emphasis on the interactions between vessels and their microenvironment. We tackle these questions by combining a wide variety of live-imaging, biochemical and molecular approaches, going from the whole animal to single-cell resolution.