Grant: Project Grant

Cisplatin is a widely used chemotherapy drug that is highly effective for treating many types of cancer. Unfortunately, it can also cause serious side effects, including permanent hearing loss, which affects up to 80% of patients who receive this treatment. Once cisplatin enters the body, it can change how genes are turned on or off in different tissues. These changes are influenced by a person's DNA and can contribute to harmful side effects such as hearing loss. Hearing depends on specialized cells in the inner ear called hair cells. These cells are particularly vulnerable to damage from cisplatin, yet they make up only a very small proportion of inner ear cells. Because of this, they have been difficult to study, and until now, no studies have examined how cisplatin affects gene activity specifically within these critical hearing cells. Recent advances in single-cell technologies now make it possible to study gene activity in individual cells, including rare cell types like inner ear hair cells. In this project, we will use these cutting-edge tools to examine how cisplatin alters gene expression in the inner ears of mice. We will combine these findings with large human genetic studies of cisplatin-induced hearing loss to identify biological patterns that help predict who is most at risk of hearing loss. Ultimately, this research aims to improve our ability to predict hearing loss before treatment begins and to identify drugs that could protect hearing without reducing the effectiveness of cancer therapy. Promising protective compounds will be tested in mouse and zebrafish models, with the goal of improving the quality of life for patients receiving cisplatin.