In this project, Dr James O’Sullivan at King’s College London explores the mechanisms associated with susceptibility to develop hearing loss when exposed to the chemotherapy drug cisplatin.
Project start date: March 2025
project end date: November 2026
About the project
Cisplatin, a common chemotherapy drug, damages cells by damaging the structures responsible for producing energy, called mitochondria. If this happens in the inner ear it can lead to irreversible hearing loss. Some people experience hearing loss after cisplatin while others don’t, this might be due to genetic variations.
One type of genetic variation is the interaction between the DNA in mitochondria and the DNA in the cell’s nucleus (the cellular structure that houses most of our DNA and genes). In some people, the mitochondrail DNA is “mismatched” to the nuclear DNA, which can result in increased vulnerability to disease.
These mismatches (called mitonuclear interactions) affect mitochondrial function, they could therefore influence how susceptible we are to cisplatin-induced hearing loss. James will explore this possibility by studying mice which are engineered to have “mismatched” mitochondrial DNA and nuclear DNA.
How it works
By studying the structure and function of the inner ear of these “mismatched” mice compared to normal mice, James aims to uncover how the interactions between mitochondrial DNA and nuclear DNA can affect the inner ear’s response to cisplatin.
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How will this research benefit people at risk of hearing loss?
By understanding how mitonuclear interactions influence the impact of cisplatin on people’s hearing, James hopes to make progress towards personalised treatments that minimise hearing loss after chemotherapy.
Furthermore, the research will shed light on the broader role of mitonuclear interactions in inner ear function, which may also be relevant in the study of hearing loss caused by other factors, such as noise exposure and ageing.
About the researcher
Dr James O’Sullivan is a Postdoctoral Research Associate at King’s College London. He was awarded an RNID-Vivensa Foundation Fellowship Grant, which began in 2025.
I think there’s still so much that we need to understand about the genetics behind why some people who receive this drug are susceptible to severe hearing loss, while others do not experience hearing loss at all.
We don’t really understand much about that variability, so I hope that my project will reveal a lot more information.”
