PROJECT SUMMARY
Proper skin restoration after the damage is vital for organismal survival. The lymphatic vascular system is spread
throughout the human body and has a critical function in mammalian physiology. In physiological conditions, its
main function is the regulation of tissue drainage, immunosurveillance, and regeneration. Lymphatic dysfunction
causes lymphedema a medical condition that manifests as tissue swelling and fibrosis. This serious condition
results in profound severe delays in wound repair and the formation of chronic non-healing wounds. The
mechanism by which lymphatic vessels regulate skin repair is unexplored. Additionally, while the role of
lymphatic vessels in immune cell egress from tissues is well-established, how lymphatic vessels may directly
modulate immune function in damaged tissues is poorly-defined. Recently, I discovered that lymphatic vessels
are actively remodeled during wound healing to form small capillaries which are present in close localization to
the wound front and hair follicles. This remodeling is critical for optimal repair as skin-specific loss of lymphatic
vessels results in a significant delay in wound closure accompanied by a massive infiltration of immune cells.
This proposal aims to leverage these observations by 1) delineating the mechanisms and consequences of
lymphatic vessel remodeling during skin repair, and 2) determining the role of lymphatic vessels and fluid
pressure in macrophage behavior during skin repair. This research stands to have a significant clinical impact
because it can serve as a basis for developing new therapeutic avenues for lymphedema ulcers and chronic
wound management. In addition, career-oriented guidance from my mentor and advisors, along with career
development activated during the K99 phase that includes formal coursework on grant writing and project
management, will further facilitate my transition to the R00 phase and my long-term productivity as an
independent academic investigator. Collectively, the proposed research and career development plans are
expected to generate data with a significant impact on understanding the repair and immunomodulatory functions
of lymphatic vessels in skin repair and setting the basis of my future research as an independent researcher.