Rudolph L. Gleason, Jr., PhD (Georgia Institute of Technology)
J. Brandon Dixon, PhD (Georgia Institute of Technology)
Alexander Alexeev, PhD (Georgia Institute of Technology)
Wei Sun, PhD (Georgia Institute of Technology)
David C. Zawieja, PhD ( Texas A&M University )
MECHANICALLY MEDIATED GROWTH AND REMODELING OF COLLECTING LYMPHATIC VESSELS
Lymphatic dysfunction plays a key role in pathologies such as immune disorders, infection, cancer, obesity, and cardiovascular disease; regarding the latter, lymphatic dysfunction may exacerbate edema in myocardial infarction (MI) and chronic heart failure. Secondary lymphedema is a progressive and debilitating disease characterized by fluid retention and tissue swelling that arises due to dysfunction in lymphatic pumping. Secondary lymphedema is a common complication in breast cancer treatment where the surgical removal of lymphatic vessels/lymph nodes can induce overloads that triggers lymphatic pathologies that can present months or even years after surgery. Although the local mechanical environment is known to regulate lymphatic function, the role of sustained mechanical overloads (e.g., high pressure and high flow) in lymphatic dysfunction has yet to be established. Towards this end, our long-term goal is to develop a mechanistic understanding of mechanically-mediated growth and remodeling (G&R) of collecting lymphatic vessels in health and disease, and to ultimately identify novel therapeutic interventions to minimize the risk of occurrence, severity, or complications of lymphatic dysfunction. The goal of my Ph.D. research is to employ a combined experimental-computationally approach to quantify the modes by which sustained high pressure and high flow compromise normal function of the lymphatic system. To accomplish these goals, we propose the following specific aims:
Aim 1: To characterize the role of mechanical overloads on growth and remodeling (G&R) of collecting lymphatic vessels via microsurgical ligation of lymphatic vessels in a novel rat tail model.
Aim 2: To characterize long-term maladaptive remodeling in a chain of lymphatic vessels via a microstructurally-motivated computational modeling framework.
From these specific aims, we will elucidate the role of mechanical stresses of lymphatic vessels through both experiment and computational modeling. Currently, most patients cannot be diagnosed until severe progression of lymphatic dysfunction. If successful, our proposal will provide a platform to better understand the modes by which mechanics impairs lymphatic structure and function, thereby providing insight into better surgical intervention and novel therapeutic strategies to prevent lymphedema.