Lymphatic Biology and Pathology

We study the mechanisms governing the development, maintenance, and regeneration of the lymphatic vasculature, and how its function and dysfunction contribute to organ-specific physiology and disease.

The lymphatic vasculature is increasingly recognized as a multifaceted regulator of tissue homeostasis and regeneration. Traditionally, its primary function has been to drain fluid, macromolecules, and immune cells from peripheral tissues into the systemic circulation via lymph nodes. Dysfunction of lymphatic vessels can lead to the accumulation of protein-rich fluid in tissues (lymphedema) and impaired immune responses. More recently, additional roles of the lymphatic system have emerged, including active modulation of adaptive immunity by lymphatic endothelial cells (LECs) and the secretion of paracrine (lymphangiocrine) factors that regulate organ growth and regeneration. These diverse functions are implicated in diseases such as autoimmune disease and atherosclerosis, underscoring the need for a better understanding of the underlying mechanisms.

Our research aims to uncover the cellular and molecular mechanisms that regulate lymphatic vessel growth, specialization, and function across tissues, and to understand how their dysfunction contributes to disease onset and progression. This knowledge provides a basis for developing novel therapeutic strategies targeting lymphatic vasculature.

A major focus of our work is to uncover tissue-specific functions of LECs in health and disease. Single-cell transcriptomics has revealed substantial heterogeneity among LECs, including the identification of a specialized PTX3+ immune-interacting subpopulation in dermal lymphatic capillaries (Petkova et al, JEM 2023). These cells contribute to lymphatic malformations by promoting immune cell recruitment and pathological vessel growth through paracrine signaling. Together, these findings highlight a dynamic crosstalk between lymphatic and immune cells and suggest broader roles for LEC-derived signals in the tissue-specific regulation of development and disease, which we continue to investigate.

In parallel, we investigate mechanisms of lymphatic vessel resilience in vivo. Using advanced intravital imaging approaches, we study LEC behavior and dynamics in living tissues at single-cell resolution. Our work has shown that cytoskeletal regulation of LEC shape is critical for maintaining vessel integrity under physiological conditions (Schoofs et al, Nature 2025). Ongoing studies aim to further define how lymphatic vessels balance structural stability with controlled permeability to ensure efficient fluid and immune cell transport.