Abstract
The lymphatics exist as an intricate one-way transport system of specialized capillaries, contractile collecting vessels (lymphangions), valves, and lymph nodes. This pumping system works in concert with the fluid demands of the tissue to move fluid, proteins, lipids, and immune (and sometimes cancer) cells against adverse pressure gradients and through lymph nodes, eventually returning fluid to the venous circulation. Recent work has shown that lymphatic pump function is extremely mechanosensitive to both changes in pressure and fluid shear stress. Given the highly abnormal loads placed on the lymphatic vasculature during disease states such as lymphedema, cancer, and chronic inflammation, it is likely that both acute and long-term mechanically mediated responses of lymphatic remodeling play an important role in the disease etiology.
To better understand the mechanisms driving growth and remodeling in the lymphatic system, we have utilized experimental approaches across multiple length scales including lymphatic endothelial and muscle cell culture, lymphatic vessel organ culture, and small (rat/mouse) and large (sheep) animal models. Informed through biaxial testing of isolated lymphatic vessels, we have developed computational models of lymphatic pumping and have verified these models through in vivo measurements of lymphatic pressure generation with a novel NIR imaging system. Applying this imaging platform to surgical models of lymphatic adaptations, paired with a volumetric growth and remodeling model of lymphatic adaptation, we are exploring responsible mechanisms of lymphatic failure. These findings have important implications not only for our ability to understand and treat lymphatic diseases such as lymphedema, but also could play a role in the compromised immune responses that are observed in various pathologies ranging from cancer to wound healing to transplant rejection.
Biography
Dr. Brandon Dixon is an Associate Professor and a Woodruff Faculty Fellow in the Woodruff School of Mechanical Engineering at Georgia Tech, where since joining the faculty in 2009 he has established a research program focused on developing engineered approaches to understanding and treating diseases of the lymphatic system. Prior to Georgia Tech, he was a post-doc at Ecole Polytechnique Federal de Lausanne (Swiss Federal Institute of Technology – Lausanne) doing research on lymphatic biology of lipid transport in the lab of Prof. Melody Swartz. Brandon received his Ph.D. in biomedical engineering in 2006 from Texas A&M University where he worked on a collaborative project with the labs of Gerry Cote, Dave Zawieja, and Jimmy Moore. He received his bachelors degree from the same university in 2001. His research is funded by the NIH, NSF, Gates Foundation, and the American Heart Association and he is a recipient of the NSF Career Award and the NIH Pathway to Independence Award.