Nishone Thompson
BME PhD Proposal Presentation

Date: 2025-08-08
Time: 1:30-3:30
Location / Meeting Link: IBB 1128 Suddath Seminar Room/ https://zoom.us/j/4045379096?omn=91543153655

Committee Members:
J. Brandon Dixon (Advisor) Ph.D.; Jennifer Spangle Ph.D., Levi Wood Ph.D., Shuichi Takayama Ph.D., Ankur Singh Ph.D


Title: Defining a novel role for miR-22 in lymphatic vessel regeneration

Abstract:
The lymphatic system is essential for maintaining fluid homeostasis, immune function and lipid uptake throughout the body. Dysfunction of the lymphatic system following injury, disease or cancer can cause debilitating diseases such as secondary lymphedema, which affects over 250 million people worldwide. Despite the prevalence and long-term disabling nature of lymphedema, treatment options remain limited, partly due to an incomplete understanding of the mechanisms that regulate lymphangiogenesis (formation of new lymphatic vessels from pre-existing ones). MicroRNAs (miRNAs), particularly miR-22, have emerged as key regulators of endothelial cell function in other disease contexts, yet their role in lymphatic endothelial cell (LEC) biology is understudied. Our preliminary findings reveal that miR-22 regulates LEC function by downregulating PROX1, the master regulator of LEC behavior and homeostasis. Furthermore, our data shows that miR-22 inhibition leads to increased VEGFR3 expression, proliferation and migration in LECs, all of which are vital to lymphangiogenesis. In this proposal, I will investigate the role of miR-22 in regulating lymphatic vessel regeneration by (1) elucidating whether PROX1 is a central target of miR-22 leading to repression of VEGFR3 signaling, migration and proliferation in LECs, (2) defining the effects of miR-22 on LEC-fibroblast signaling in lymphatic sprout formation, (3) exploring how stiffness-induced upregulation of miR-22 influences lymphatic sprouting and (4) whether miR-22 modulation may serve as a therapeutic strategy in lymphedema when delivered in vivo via a LEC-specific lipid nanoparticle. Understanding mechanisms through which miR-22 regulates LEC homeostasis and post-natal lymphangiogenesis may ultimately provide new targets to treat secondary lymphedema.

Wallace H. Coulter Department of Biomedical Engineering

Georgia Institute of Technology and Emory University

313 Ferst Drive

Atlanta, GA 30332

www.bme.gatech.edu