Advisor: Susan Thomas, Ph.D. (Georgia Institute of Technology)
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 LOCAL INFLAMMATORY DISEASE
Local inflammation within tumors and injured joints is implicated in the systemic side effects that precipitate development of more advanced pathologies, such as metastasis and rheumatoid arthritis (RA), respectively. Soluble factors (SF) produced within the tissues of localized disease, 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 course on their dissemination profiles is poorly defined. This stymies progress towards therapeutic amelioration of SF signaling activities to improve disease outcome and is the critical knowledge gap this proposal seeks to fill. The central hypothesis is that vascular remodeling within diseased tissues redirects the organism-wide signaling activity of locally secreted SF and may negatively contribute to disease burden by altering the bioavailability of molecules important to systemic disease progression. The overall objective of this proposal is to elucidate how local tissue remodeling may lead to pathological signaling within distributed tissues in order to provide insight into the potential for localized disease to exert systemic effects.