Publication Date

2024

Document Type

Thesis

Committee Members

J. Ashot Kozak, Ph. D. (Advisor); Dawn Wooley, Ph.D. (Committee Member); Marjorie M. Markopoulos, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Calcium signaling is a crucial regulator in many cellular processes, from immune response modulation to gene expression and apoptosis. Here, I have investigated the dynamics of calcium entry pathways, namely, store-operated calcium entry and store-independent calcium entry using a variety of cell types such as Jurkat T cells, HEK-293 cells and murine macrophages. Using fluorescence calcium imaging and selective inhibitor compounds, I have investigated the contributions of Orai and related calcium channels to calcium entry in both immune and non-immune cell types. The results demonstrate the pharmacological modulation of store-operated and store-independent calcium entry, showing the ability of compounds such as AE-19, AE-10, and EL-113 to inhibit calcium entry. Experiments involving membrane depolarization with elevated potassium concentrations confirmed that calcium entry through the plasma membrane is membrane potential-dependent. My results highlight the medical relevance of these channels, especially in the process of tubular aggregated myopathy, immune regulation and cancer. My studies may lead to therapeutics targeting calcium signaling pathways relevant to immune and muscular disorders.

Page Count

68

Department or Program

Microbiology and Immunology

Year Degree Awarded

2024


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