New U01 Awardee Presentation
Title: Fluid Pumping and Mass Transfer in the Lymphatic System
Abstract:
The lymphatic system has many recognized important roles in normal physiology and in a variety of disease conditions. In addition to returning fluid from interstitial tissue spaces to the blood circulation, it also serves as an important transport route for immune cells. Lymph nodes are important sites for cellular interactions involved in immunity, inflammation and fluid balance. Transport phenomena and/or breakdowns in lymphatic system performance are crucial, or at least involved in, cardiovascular diseases, cancer, obesity and injury resolution. Despite the importance in so many causes of death and disability, little is actually known about transport mechanisms in this obscure system.
We have developed models of lymphatic system pumping based on a multiscale approach, combined with a unique experimental skill set. In addition to the general insight on lymphatic pumping, we have elucidated the phenomena by which the lymphatic system is able to generate negative interstitial tissue pressures while still generating positive fluid flow out of those tissues. This resolves a decades-old mystery of basic physiology. Our results have also identified two physical properties of lymphatic vessel behavior that are crucial for effective pumping. The first is the resistance of lymphatic valves to both forward and reverse flows, and how they switch from the closed to the open position and back. The second is the unique abilities of lymphatic muscle cells (LMC) to contract over a wide range of vessel diameters. Our current experimental and modeling work is focused on quantifying these parameters better.
We are also beginning to incorporate important fluid flow phenomena in lymph nodes. These are highly compartmentalized structures in which leukocytes process antigens, foreign bodies and tumor cells. There are also specialized direct communication ports with the blood circulation in which fluid and cells can traverse in either direction.
The results of this research will include the most advanced model of lymphatic transport and function to date, the ability to predict the effects of interventional procedures, and the optimization of those procedures for the benefit of the numerous patients suffering from lymphatic associated diseases.
Biosketch:
Dr. Moore received his Bachelor of Mechanical Engineering in 1987, his Master of Science in Mechanical Engineering in 1988 and his Ph.D. in 1991, all from the Georgia Institute of Technology. He had postdoctoral training at the Swiss Institute of Technology at Lausanne, 1991 – 1994. Prior to moving to Imperial College London in 2013, Dr. Moore worked at Texas A&M University, where he served as the Carolyn S. and Tommie E. Lohman ’59 Professor of Biomedical Engineering and Director of Graduate Studies. He currently serves as the Bagrit and Royal Academy of Engineering Chair in Medical Device Design, and Director of Research for the Department of Bioengineering.
Dr. Moore’s research interests include Cardiovascular Biomechanics, Stents, Implantable Devices, Atherosclerosis, and the Lymphatic System. His research focuses on the role of biomechanics in the formation and treatment of diseases such as atherosclerosis and cancer. His research on lymphatic system biomechanics, initiated in 2004 with Dr. David Zawieja, has provided unprecedented insight into the pumping characteristics of the system and the transport of nitric oxide, antigens, and chemokines in lymphatic tissues. He is currently developing two technologies for preventing and resolving secondary lymphedema, which typically forms subsequent to cancer surgery. Along with his funding from government, charity, and industry sources, Dr. Moore has received multiple patents for medical devices and testing equipment. Dr. Moore has also co-founded two startup companies.