Date of Award

Spring 2026

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

First Advisor

Kaho Leung

Abstract

Chloride is the most abundant intracellular anionic species and a critical regulator of cellular homeostasis. Whose involvement in processes ranges from neuronal signaling to innate immunity. However, in contrast to other ionic species, significant investigation of intracellular chloride dynamics has remained limited. This limitation is primarily due to the lack of development in adequate chloride reporters. This work develops and applies advanced imaging strategies to further elucidate the role of chloride across cellular health and disease. Here we introduce pH-independent, photostable halide indicators, including a fluorescence lifetime-based iridium(III) complex and small molecule cytosolic dyes, enabling visualization of Cl⁻ fluxes in live cells. Using these developed tools, we uncover dysregulated chloride dynamics in neurodegenerative disease models and develop a CFTR function assay. Lasty, utilizing our small molecule reporter we discovered chloride efflux as a permissive regulator of cGAS–STING signaling. Giving critical mechanistic insight into a previously unknown aspect of STING signaling. Together, these studies further the resources available for cellular chloride investigation and elucidate chloride as a biologically essential ion whose regulation spans from disease physiology to innate immunity.

Rights

© 2026, Jared M. Morse

Available for download on Monday, May 31, 2027

Included in

Chemistry Commons

Share

COinS