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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Advisor: Susan N. Thomas, Ph.D. (Georgia Institute of Technology)
Committee:
Krishnendu Roy, Ph.D. (Georgia Institute of Technology)
Edward Botchwey, Ph.D. (Georgia Institute of Technology)
Fredrik Vannberg, Ph.D. (Georgia Institute of Technology)
Edmund Waller, M.D., Ph.D. (Emory University)
ROLE OF VASCULAR REMODELING IN THE ACCUMULATION, CLEARANCE, AND BIODISTRIBUTION OF BIOMOLECULAR FACTORS IN MELANOMA
Local inflammation within the tumor microenvironment is implicated in the systemic effects of disease progression, such as immune suppression and metastasis. Soluble factors (SF) produced within the tumor, including cytokines, exosomes, proteases, and microvesicles, mediate pathological signaling and have emerged as putative therapeutic targets. However, SF bioavailability in distributed tissues and the impact of disease progression on their dissemination profiles and exposure to various immune cell subsets is poorly defined. This stymies progress towards therapeutic amelioration of SF signaling activities to improve disease outcomes and is the critical knowledge gap this thesis seeks to fill. The central hypothesis is that tumor vascular remodeling redirects the organism-wide exposure of SF secreted locally within the tumor microenvironment, which may negatively contribute to disease burden by altering the bioavailability of molecules important to systemic disease progression. In this thesis, the effects of local tissue remodeling in melanoma leading to pathological SF accumulation profiles within distributed tissues are elucidated in order to provide insight into the potential for localized disease to exert systemic effects and inform opportunities to develop better preventive and curative treatment options for advanced melanomas.
