Nishone Thompson
BME PhD Defense Presentation

Date: 2026-08-21
Time: 2pm
Location / Meeting Link: MoSe 1224/ https://zoom.us/j/4045379096?omn=97948521078

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


Title: DEFINING A NOVEL ROLE FOR MIR-22 IN LYMPHANGIOGENESIS

Abstract:
The lymphatic system plays an essential role in fluid homeostasis, immune surveillance, and dietary lipid absorption. Impaired lymphatic function can lead to lymphedema, a chronic and progressive disorder characterized by tissue swelling, inflammation, and fibrotic remodeling. Despite its significant impact on patient quality of life, effective therapies that address the underlying causes of lymphatic dysfunction remain limited. This dissertation investigates the role of microRNA-22 (miR-22) in the regulation of lymphangiogenesis, the process by which new lymphatic vessels form from pre-existing ones. Online TargetScan bioinformatic analyses identified miR-22 as a potential regulator of prospero homeobox protein 1 (PROX1), a master transcription factor that governs lymphatic endothelial cell identity and function. Through a combination of in vitro, multicellular spheroid platform, and in vivo studies, this work examines how miR-22 influences lymphatic endothelial cell behavior and lymphatic vessel growth. The findings demonstrate that inhibition of miR-22 enhances key lymphangiogenic processes, including lymphatic endothelial cell proliferation, migration, and network formation, while promoting activation of the PROX1/VEGFR3 signaling pathway. In addition, this work highlights the importance of the cellular microenvironment in regulating lymphangiogenesis given than in our multicellular spheroid platform, sprouting decreased with miR-22 inhibition. Finally, this work explores the therapeutic potential of lipid nanoparticle-mediated delivery of a miR-22 inhibitor in a mouse model of lymphedema. Collectively, these studies identify miR-22 as a novel regulator of lymphatic vessel growth and provide a foundation for the development of miRNA-based therapeutic strategies aimed at improving lymphatic regeneration and treating lymphatic disease.