1. Can you please briefly summarize the paper? 

We study cisplatin, which is a widely used and effective anticancer drug, but it has significant side effects, including ototoxicity (hearing loss) and nephrotoxicity (kidney injury), in pediatric and adult cancer patients. In this paper, we investigated the role of macrophages in cisplatin-induced hearing loss and kidney injury in mice.

Following systemic administration of cisplatin, macrophage ablation using PLX3397 (small molecule CSF1R inhibitor) resulted in a significant protection against cisplatin-induced hearing loss and kidney injury, in part by limiting cisplatin accumulation in the cochlea (hearing organ) and the kidney. In other words, our study suggests that less cisplatin enters and accumulates in the cochlea and kidney when macrophages are ablated. As a result, the reduced cisplatin exposure protects cells in these organs from cisplatin-induced toxicities.

This figure is a snippet of our findings showing that mice exposed to cisplatin in the presence of macrophages (red line) developed significant hearing loss, while mice exposed to cisplatin in the absence of macrophages (green line) maintained normal hearing (and did not develop hearing loss).

2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?

The biggest difficulty I encountered was performing experiments during the COVID-19 pandemic. The pandemic caused significant disruptions, including restricted lab access, delays in obtaining essential experimental items and reagents, and limited availability of animal staff. This led to a reduction in the number of animals we could maintain, which was particularly challenging since our study relied heavily on mice for the cisplatin administration protocol. As lab access was gradually restored, I focused on maximizing productivity while strictly adhering to safety guidelines, which allowed the project to continue making progress despite the challenging conditions.

Experimentally, it was challenging to identify a method for administering PLX3397 via the oral gavage in mice. The solvent typically used to dissolve PLX3397 includes dimethylsulfoxide (DMSO), which has been shown to cause hearing loss. Since our goal was to assess hearing after cisplatin administration, we decided to use a solvent that does not contain DMSO. When using solvent without DMSO, I encountered issues with PLX3397 easily falling out of solution. To address this issue, I prepared two separate solutions: one with PLX3397 dissolved in PEG300 (one component of the solvent) and another with Tween80/Saline for long-term storage. I then combined these solutions immediately prior to administration via oral gavage, ensuring that minimal to no PLX3397 precipitated out of solution before it was administered to mice.

3. Please introduce your laboratory, university or organization to bio-researchers in Korea.

This study was performed at the National Institute on Deafness and Other Communication Disorders (NIDCD) within the National Institutes of Health (NIH). The NIH is the leading U.S. government agency for biomedical and public health research. While NIH is widely recognized as a funding agency for external research institutions (non-NIH) through its Extramural Research Program, NIH also conducts its own scientific research through the Intramural Research Program (IRP). Comprising 27 Institutes and Centers (ICs), the NIH has approximately 1,200 Principal Investigators and nearly 5,000 trainees ? including postbaccalaureate, postdoctoral fellows, and graduate students in Graduate Partnership Programs ? engaged in biomedical research within the Intramural Research Program.

Within NIDCD, I am fortunate to be part of the Laboratory of Hearing Biology and Therapeutics, led by Dr. Lisa Cunningham. Her team conducts basic, translational, and clinical research focused on hair cell degeneration and hearing loss in mature inner ears and develops therapeutic strategies to protect hearing, specifically against ototoxic drugs. Additionally, this study was conducted in collaboration with Dr. Mark Warchol, my co-mentor, from Washington University in St. Louis, who investigates the role of macrophages in the development, pathology, and regeneration of sensory receptors in both the mammalian inner ear and the zebrafish lateral line. Finally, since cisplatin also leads to significant kidney injury, we collaborated with Dr. Robert Star’s lab at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to show that macrophage ablation with PLX3397 offers protection against cisplatin-induced kidney damage.

Here, I have been surrounded by dedicated scientists and cutting-edge resources that have greatly deepened my understanding of auditory science and therapeutic development. Being a part of this highly collaborative and impactful group has been an incredible experience. I am especially grateful for the opportunity to integrate my own research interest in cochlear immunology into the project, allowing me to contribute meaningfully while exploring areas I am passionate about. This experience has further solidified my commitment to uncover the biological mechanisms underlying the roles of immune cells in the cochlea and harness it to preserve hearing, ultimately improving the quality of life for individuals affected by hearing loss.

4. Please tell us your experiences and your thoughts related to research activities abroad.

I completed my undergraduate and graduate studies, as well as my current postdoctoral position, all in the United States. As a result, I am less familiar with the research environment in Korea. However, my experience in the United States has shown that the training for developing young scientists is rigorous and strongly emphasizes fostering independence in their research. The research landscape is highly competitive, but it provides significant advantages, including numerous grants and fellowships that support a wide range of research projects. Researchers often work in interdisciplinary teams, fostering collaboration across various fields and utilizing cutting-edge technologies. Additionally, there is a strong focus on translating basic research into clinical applications, which drives many institutions to engage actively in basic research, as it often forms the foundation for translational science. Finally, the research environment encourages international collaborations, providing opportunities for global partnerships and knowledge exchange.

5. Can you provide some advice for younger scientists who have plans to study abroad?

Wherever you go, regardless of the country, focus on finding excellent mentors who can support your professional growth and conduct high-quality science, irrespective of the institution’s reputation. Building strong relationships with your mentors can provide invaluable guidance and help you navigate the unfamiliar research environment more effectively.

6. Future plan?

I will be starting my independent laboratory in the Department of Biology at the University of Iowa in August 2025. My research program will focus on identifying the roles of macrophages during ototoxic drug-induced hearing loss with interests including investigating the biology of the blood-labyrinth barrier in the inner ear. From these studies, I aim to identify therapeutic targets or develop therapeutic drugs to prevent ototoxic drug-induced hearing loss. By leveraging knowledge from cochlear immunology and advancing these therapeutic strategies, I plan to progress towards conducting clinical trials and translating laboratory findings into real-world clinical applications.

If you are interested in this work, please reach out!

7. Do you have anything else that you would like to tell Korean scientists and students?

There will always be hard moments during research, but stay excited about your science and stay curious! The passion you bring to your work will help you push through challenges and continue making progress!