Document Type

Proposal

Publication Date

Spring 2025

Department

Biological & Environmental Sciences

Faculty Advisor

Dr. Amorette Barber

Abstract

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. Cl-amidine is a small organic compound that irreversibly inhibits PAD4, and has been shown to induce the p53 pathway in numerous cancers. However, Cl-amidine and similar compounds have not yet been used against ovarian cancer. In addition, Cl-amidine has been reported to exhibit synergism with rapamycin, an established anticancer drug, and therefore has the potential to participate in a co-treatment. This proposal will investigate the effect that Cl-amidine alone and in conjunction with rapamycin has on the apoptosis and gene expression of ovarian cancer cells.

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