Published June 5, 2023
Jason Sprowl, PhD, assistant professor, Department of Pharmaceutical Sciences, has been awarded a $432,182 grant from National Institute on Deafness and Other Communication Disorders (NIDCD) and the National Institutes of Health (NIH). The study, called “Role of MCT6 in mediating cisplatin-induced ototoxicity,” will help researchers understand and prevent a prevalent type of drug-induced hearing loss in cancer patients.
Cisplatin is one of the most widely used anti-cancer drugs, but it can cause cellular damage that leads to severe dose-limiting hearing loss in up to 70% of patients who take the drug. Past studies suggest that patients with reduced function in a specific membrane transporter, MCT6, were not as susceptible to the adverse effects of cisplatin on their hearing. This finding led to the current grant, which proposes a series of experiments to study the role of MCT6 in regulating cellular uptake of cisplatin metabolites and cisplatin mediated hearing loss with the goal to develop strategies to prevent this outcome.
“The grant will help us clarify the role and impact that the MCT6 protein has in moving a cisplatin metabolite into cells,” explains Sprowl. “Furthermore, we will confirm if loss of the protein’s activity (through genetic deficiency) can be protective of cisplatin-induced hearing loss. We will also see if there are any other unexpected effects that could arise from cisplatin treatment in the absence of this protein, which would provide feasibility and clarity on developing pharmaceutical drugs to target MCT6.”
This study is a continuation of some of Sprowl’s earliest research interests, during which he saw the potential to improve oncology patient outcomes firsthand.
“I worked with cisplatin toxicities during my postdoc at St. Jude Children’s Research Hospital and even met children that had experienced hearing loss during treatment,” says Sprowl. “Finding ways to predict those who would experience toxicity would be ideal and finding proteins such as MCT6 that could be targeted pharmaceutically could open the door to combination therapy that would allow us to treat cancer but reduce toxicities such as hearing loss.”
The study’s co-investigator is Bo-Hua Hu, PhD, department chair and associate professor in UB’s Department of Communicative Disorders and Sciences. The multidisciplinary collaboration between Sprowl and Hu has the potential to yield even more robust and actionable study findings.
“Bo-Hua has immense knowledge in hearing assessment and mechanics and merging his capabilities and knowledge with our own expertise in drug pharmacokinetics, pharmacogenomics and toxicities will be a key to developing strategies that can be used clinically to reduce hearing loss triggered by cisplatin treatment,” says Sprowl. “Our groups have met several times to discuss data and it’s clear that having multiple interdisciplinary teams looking at experimental findings certainly strengthens our interpretation of their meaning.”