Advisor: Susan Thomas, Ph.D. (Georgia Institute of Technology)

Committee:

M.G. Finn, Ph.D. (Georgia Institute of Technology)

Brandon Dixon, Ph.D. (Georgia Institute of Technology)

Valeria Milam, Ph.D. (Georgia Institute of Technology)

Michael Davis, Ph.D. (Georgia Institute of Technology, Emory University)

BIOMATERIALS-BASED NANOTECHNOLOGY FOR LYMPHATIC-TARGETED NITRIC OXIDE MODULATION

The lymphatics play a vital role in the regulation of tissue fluid levels and immune response. Loss of lymphatic function leads to accumulation of interstitial fluid (edema), tissue damage, loss of lipid transport, increased adipocyte differentiation (obesity), and downregulated immune function. Alleviating lymphatic dysfunction therefore represents a critical hurdle in the treatment of many pathologies. Nitric oxide (NO) is among the principal signaling molecules controlling lymphatic function when it is produced in physiological levels, and is also integral in the cytotoxic immune response of leukocytes where it is produced it high concentrations and can react with other inflammatory species. Therefore, corruption of NO signaling is associated with the initiation and/or propagation of many lymphatic pathologies. Given the importance of the lymphatics and the pronounced effect NO has on lymphatic and immune function, modulation of NO within lymphatics offers a promising means of alleviating lymphatic deficiencies that may arise from loss of function or parasitic infection, and which eventually contribute to many diseases. To date, however, clinical application of NO modulation within lymphatics has been hindered by the lack of adequate vehicles to both deliver and modulate NO levels in a controlled manner. The objective of this proposal is to develop a biomaterials-based approach to improve the efficacy of NO modulation within lymphatic tissues.