Speaker: Hyun-Min Jung, University of Illinois at Chicago assistant professor of pharmacology

Title: New mechanisms of lymphangiogenesis in development and disease

Abstract: The lymphatic system is essential to maintain fluid balance in our body by collecting interstitial fluid and transporting it back to circulation. Failure of this system causes excessive fluid accumulation that leads to devastating incurable diseases such as lymphedema. Treatment options for lymphedema are very limited due to biological complexity and lack of targets. Therefore, better understanding of lymphatic vascular biology and developing strategies to regenerate lymphatic vessels are immediate needs to cure lymphedema. We use genetics, live imaging, and modern molecular biology approaches to study the development and function of lymphatic vessels using zebrafish as a model organism. Learning from developmental biology, the goal is to learn how to regenerate lymphatic vessel. Our understanding of lymphatic vessel development comes largely from functional characterization of transcription factors, growth factors, and their corresponding receptors, which together have greatly advanced the understanding in this research area. The current paradigm of lymphangiogenesis heavily focuses on the inductive mechanisms driven by transcription factors in venous endothelial cells (ECs) that trigger transdifferentiation into lymphatic precursors to express FLT4 (VEGFR3), which are then attracted towards a VEGFC gradient. Considering the highly plastic nature of ECs, tight cell-specific regulatory mechanisms are necessary to control EC identity during lymphangiogenesis. However, compared to intensive research focused on the inductive mechanisms of lymphangiogenesis, the inhibitory mechanisms that change venous cell properties to promote lymphatic vessel development remain unclear. In this study, we show our recent discovery of a lymphatic-enriched microRNA that promotes lymphangiogenesis. Our loss-of-function models using morpholino or CRISPR-mediated genome editing display severely impaired lymphatics but massive venous growth in these animals indicating that miR-204 is essential for venous-to-lymphatic EC differentiation Hence, manipulating miR-204 in ECs represents a promising strategy to regenerate lymphatic vessels.

Host: Xiaoyi Cheng, GDCB Graduate Student Postdoc Organization president and GDCB graduate student in Espin Palazon Lab