1. Can you please briefly summarize the paper? 

Our research aimed to address a long-standing challenge in hearing loss therapy: how to generate functional cochlear hair cells in the lab. These cells are responsible for converting sound vibrations into electrical signals that the brain can interpret. In humans, once these cells are damaged-due to aging, noise, or drugs-they do not regenerate. To model and potentially restore them, we used inner ear organoids, 3D mini-organs grown from progenitor cells that mimic the structure and function of the cochlea.

We focused on a specific population of cochlear progenitor cells marked by Lgr5, a well-known stem cell marker in the inner ear. By isolating these Lgr5-positive cells using a technique called magnetic-activated cell sorting (MACS), we created a homotypic organoid culture, free from other cell types that might interfere with or mask their development. Although these progenitor cells successfully differentiated into hair cell-like cells, they initially lacked the mature structures-specifically stereocilia-that are essential for sensing sound.

To overcome this, we turned to developmental biology. We found that activating the Sonic Hedgehog (Shh) signaling pathway, especially in combination with Wnt inhibition, significantly improved the structural and functional maturation of these lab-grown hair cells. This was confirmed through electron microscopy, FM1-43 uptake assays (a test for functional hair cells), and single-cell RNA sequencing, which showed upregulation of key structural genes like Pls1, Lmo7, and Lrba-all involved in forming the cuticular plate, a base for stereocilia anchoring.

Finally, we co-cultured these mature organoids with spiral ganglion neurons, which normally carry sound signals from the ear to the brain. The co-cultures showed functional electrical activity, similar to native cochlear tissue, as measured by microelectrode array recordings. This suggests that not only did the cells mature structurally, but they were also capable of forming functional synapses. Overall, our work demonstrates a new strategy for generating more realistic and functionally relevant inner ear organoids, which could accelerate both basic research and therapeutic development in hearing loss.

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

While generating hair cell-like cells from Lgr5-positive progenitors was achievable, these cells often lacked the proper structural features-especially the organized, bundle-like stereocilia required for mechanoelectrical transduction. It was frustrating because, morphologically, they looked like hair cells, but functionally, they were immature.

To tackle this, we first went back to the transcriptomic data to identify which developmental pathways were underactive. We found that genes related to morphogenesis were significantly downregulated in our homotypic MACS-derived cultures. This led us to explore the Sonic Hedgehog (Shh) signaling pathway, which is known to influence epithelial patterning during development. After careful optimization of the culture timeline and small molecule treatments, we introduced Shh activation alongside Wnt inhibition. This combination ultimately promoted stereocilia formation and functional maturation, which we validated using imaging, uptake assays, and single-cell sequencing.

Another technical hurdle was achieving clean and reproducible isolation of Lgr5-positive cells. Manual isolation often introduced unwanted cell types that confounded results. Switching to MACS helped tremendously, but we still had to carefully standardize the dissociation and sorting protocol to maintain cell viability and ensure high purity. We also faced challenges with 3D culture consistency-such as variations in Matrigel handling and organoid morphology-which we managed by rigorously timing media changes, monitoring cell density, and pre-aliquoting reagents to minimize variability.

Overall, the key was persistence, careful troubleshooting, and integrating molecular insights with experimental refinements. Every setback led us to re-examine the biology, which made our findings stronger in the end.

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

This research was conducted at Dankook University, mainly through a collaboration between the Beckman Laser Institute Korea, the Department of Otolaryngology-Head and Neck Surgery, and the Department of Cosmedical & Materials. Dankook University, located in Cheonan, South Korea, is a multidisciplinary research hub known for its growing strengths in regenerative medicine, biomedical engineering, and laser-based medical applications.

The Beckman Laser Institute Korea played a central role in integrating optical techniques and organoid culture systems, especially in the design of functional assessments like live imaging and microelectrode array recordings. The Medical Laser Research Center and Department of Otolaryngology-Head and Neck Surgery provided critical expertise in inner ear biology, cochlear development, and neural co-culture experiments.

Importantly, the Department of Cosmedical & Materials contributed significantly to the transcriptomic analyses, including both bulk and single-cell RNA sequencing (scRNA-seq). Their support enabled us to perform high-throughput gene expression profiling and in-depth computational analysis, which were crucial for identifying molecular changes during hair cell differentiation and maturation.

This collaborative environment-spanning molecular biology, bioengineering, and clinical sciences-was essential for executing a study that bridges developmental biology and translational hearing research.

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

I’m originally from the Philippines, and coming to Korea to pursue research was both a bold decision and a deeply meaningful one for me. I was drawn not only by Korea’s advanced biomedical infrastructure, but also by its strong emphasis on translational research and interdisciplinary collaboration-especially in areas like regenerative medicine and neuroscience. Being able to immerse myself in a country that invests heavily in cutting-edge science gave me access to techniques, equipment, and mentorship that would have been much harder to access back home.

Of course, adjusting to a new environment had its challenges. Language barriers, cultural differences, and being away from family were not easy, especially in the beginning. But I was fortunate to be part of a supportive and internationally minded research group that valued open communication and teamwork. Over time, I’ve come to really appreciate the collaborative spirit here in Korea, where researchers from diverse disciplines often come together to tackle complex biomedical questions.

One of the most valuable things I’ve learned is how diversity in perspective enriches scientific inquiry. Coming from a different cultural and academic background allowed me to ask questions others might not think of, and to approach problems with fresh angles. I believe that global mobility in science is a strength-it allows us to share not just tools and data, but also values and vision.

Ultimately, this experience has strengthened my commitment to research and to building bridges between scientific communities in Southeast Asia and Korea. I hope to contribute to a future where research is more collaborative, inclusive, and globally impactful.

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

Studying or doing research abroad is a transformative experience-not just for your career, but for your growth as a person. If you’re considering this path, my first advice is to be clear about your motivation. Know why you want to go abroad. Is it to learn a specific technique, work with a particular mentor, or broaden your academic network? Having a clear purpose will keep you grounded when things get tough-which they will, at times.

Second, prepare to adapt and stay humble. You’ll encounter different research cultures, communication styles, and work expectations. At times, language or cultural differences might make you feel out of place. That’s completely normal. What matters is your willingness to learn-not just new scientific methods, but also how to be part of a different academic community. Respect and curiosity will take you far.

Third, build relationships intentionally. Don’t isolate yourself in the lab. Seek out mentors, collaborators, and friends. These relationships will become your professional network, your support system, and often, your lifelong friends. Some of the best insights and opportunities in my journey came from casual conversations over coffee or during lab meetings.

Lastly, don’t forget your roots. Bring your background, your values, and your voice with you. Diversity in science is powerful. Your perspective as a researcher from your home country can contribute something truly unique. And when you succeed, you can become a bridge for others who dream of following a similar path.

6. Future plan?

Moving forward, I hope to continue exploring how stem cell biology and tissue engineering can be harnessed to regenerate the inner ear and restore hearing. Our recent work on enhancing stereocilia maturation in organoids is just the beginning. There’s still a lot to learn-especially about how to fully recapitulate the functional complexity of native cochlear hair cells, and how to make these cells integrate reliably in vivo.

In the short term, I plan to build on this research by investigating long-term maturation protocols, improving the electrical integration with neural circuits, and testing these organoid models in more advanced co-culture and transplantation systems. I also want to expand this model to include genetic hearing loss conditions, using CRISPR or patient-derived iPSCs, to better understand disease mechanisms and screen potential therapies.

In the long run, I aspire to lead a research group that bridges the gap between basic science and clinical translation. Ultimately, I see myself working at the intersection of regenerative biology, bioengineering, and translational medicine-developing not just knowledge, but actual tools that can make hearing restoration a reality.

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

First, I want to express my sincere gratitude to the Korean scientific community. As a foreign researcher, I’ve received so much support, guidance, and encouragement here. Korea’s strong investment in science and its welcoming research environment have truly helped me grow-not only as a scientist, but as a person. I’m especially thankful to my mentors and labmates who treated me not as an outsider, but as a colleague and collaborator.

To Korean students and young scientists: your research environment is incredibly rich in opportunity, from cutting-edge facilities to multidisciplinary collaborations. I hope you fully explore it with curiosity and confidence. At the same time, I encourage you to look beyond borders. Whether through international conferences, joint projects, or studying abroad, you’ll find that science becomes even more meaningful when shared across cultures.

Don’t be afraid to ask big questions, even if the answers take time. Stay curious, stay kind, and stay committed to discovery. The world needs your ideas and your passion-not only to advance knowledge, but to make science more global, inclusive, and human-centered.

And if ever you meet a fellow researcher from abroad-whether from the Philippines or elsewhere-I hope you’ll show them the same warmth and generosity that I’ve received here. It truly makes a difference.