Lauren Liebman
BME PhD Proposal Presentation

Date:2022-02-03
Time: 8:30 AM
Location / Meeting Link: IBB Suddath Room, https://bluejeans.com/965751828/9658

Committee Members:
J. Brandon Dixon, PhD (Advisor); Edward Botchwey, PhD; Zachary Buchwald, MD, PhD; Andres Garcia, PhD; Johnna Temenoff, PhD


Title: Investigation of and therapeutic intervention in the crosstalk between inflammation and lymphatic function

Abstract: The lymphatic system is a complex network of lymphatic vessels, lymph nodes, and lymphoid organs responsible for transporting interstitial fluid, lipids, macromolecules, and immune cells. Crosstalk between inflammation and lymphatic function is a hallmark of numerous pathologies, including lymphedema—a disease that often arises following lymphatic damage by cancer treatment. Application of specialized pro-resolving mediators (SPMs) is a potential approach to rescue lymphatic function and attenuate inflammation to treat inflammatory diseases. The proposed work will investigate crosstalk between inflammation and lymphatic function in two murine models: a radiotherapy model for the treatment of melanoma and a surgical model of lymphedema. We will evaluate lymphatic function and remodeling after radiotherapy with and without surgical disruptions of lymphatic vessels in a mouse model of metastatic melanoma (Aim 1). We will also investigate effects of SPM treatment on lymphatic endothelial cells (LECs) and lymphatic muscle cells in multiple in vitro studies: transwell assays to evaluate LEC permeability following treatment and application of our laboratory’s custom three-dimensional spheroid platform to evaluate lymphangiogenic response to treatment (Aim 2). In Aim 3, we will evaluate sustained delivery of SPMs as a therapeutic strategy to resolve lymphatic injury in a surgical mouse tail model of lymphedema. Mice will be injected with SPM-loaded polymeric particles that have been optimized to prolong SPM release. In total, these studies will further our understanding of interactions between inflammation and lymphatic function and will establish a new therapeutic strategy for lymphatic injury.