Kahn Lab

Lymphatic and Blood Thrombotic Vascular Signaling

Regulation of blood and lymphatic clotting is crucial for development and healing.

The lymphatics arise from the blood vascular system and are important in tissue healing after injury. As a one-way system, the lymphatics utilize valves to prevent backflow of fluid. Both the blood and lymphatic systems utilize anti-thrombotic mechanisms to prevent clotting. Our lab has a longstanding history of studying the mechanism of platelet activation in which lymphatic endothelial Podoplanin activates platelet CLEC2 receptors to drive an inter-vascular form of hemostasis known as lympho-venous hemostasis. More recently, our lab has shown that movement of lymph fluid through lymphatic vessels is important to promote lymphatic valve development (JCI 2015) and prevent clots in blood vessels (JCI 2019). Furthermore, damage to lymphatics prevents healing after injury (JCI 2019, Blood 2019). We are now investigating the role of lymphatics and thrombosis in other organs, such as the gut, heart, and placenta in development and response to injury.

Collaborating Labs

• Igor Brodsky (University of Pennsylvania)
• Joshua Scallan (University of South Florida)

See the below recent publications related to this project:

Sinusoidal and lymphatic vessel growth is controlled by reciprocal VEGF-C-CDH5 inhibition

Sung et al. 2022, Nature Cardiovascular Research. https://www.nature.com/articles/s44161-022-00147-0

Genetic blockade of lymphangiogenesis does not impair cardiac function after myocardial infarction

Keller et al. 2021, Journal of Clinical Investigation. https://www.jci.org/articles/view/147070

Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis

Welsh et al. 2019, Journal of Clinical Investigation. https://www.jci.org/articles/view/124791

John and his paper were featured on the podcast "Beyond the Abstract." Listen here.

Hemostasis stimulates lymphangiogenesis through release and activation of VEGFC

Lim et al. 2019, Blood. https://doi.org/10.1182/blood.2019001736

Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage

Reed et al. 2019, Journal of Clinical Investigation. https://www.jci.org/articles/view/125044

Lymph flow regulates collecting lymphatic vessel maturation in vivo

Sweet et al. 2015, Journal of Clinical Investigation. https://www.jci.org/articles/view/79386