Member: Hearing Restoration Project
Current Institution: University of Washington
Education: Cornell University, B.Sc.; University of Pennsylvania, Ph.D.; University of Oregon, Postdoctoral training
What is your area of focus?
My lab is interested in understanding why hair cells in the inner ear (cochlea) die in response to damage, and how these damaged hair cells can be replaced through regeneration. We study these questions using the zebrafish as a model system: Zebrafish hair cells are located on the surface of their body, in the lateral line system, and are used to detect water flow. These lateral line hair cells are very similar to those of the mammalian inner ear but for scientists, they have the added advantage of easy access for visualization and manipulation. They also respond to damaging agents that affect humans, including therapeutic (ototoxic) drugs that have the unwanted side effect of killing hair cells and causing irreversible hearing loss. In addition the lateral line system undergoes robust regeneration after damage, and thus provides an interesting opportunity to compare that process with what fails to occur in mammals.
Why did you decide to get in to scientific research?
I was always fascinated by puzzles and problem solving, the discovery of new ideas, and figuring out how things work. As a small child I wanted to be an archaeologist, uncovering clues to the past. Perhaps I was intrigued by the idea of digging up treasure, but the process of discovery appealed to me, especially the potential to find new knowledge about the past. As a scientist I am still excited about the potential to discover the unknown.
Why hearing research?
My Ph.D. and postdoc training was in molecular genetics and nervous system development. It was my colleague, retired Hearing Restoration Project (HRP) consortium member Edwin Rubel, Ph.D., who convinced me to look at hearing and hair cells. Together, we recognized that the strengths of the zebrafish system could be applied to studying hair cell function and dysfunction. That was 15 years ago and we’ve been collaborating ever since.
Before entering the field of hearing research I did not recognize how pervasive hearing loss is in this country and around the world. Understanding the causes of hearing loss and discovering potential therapies to alleviate its repercussions are incredibly challenging. Along with every member of the HRP consortium, I hope that bringing new approaches to the table will help contribute to mitigating these challenges.
What is the most exciting part of your research?
The most exciting parts of our research are reflective of the growing ability to apply new technologies to understanding hair cell regeneration. Gene editing capabilities allow us to test the function of genes in a previously unprecedented way, while advances in microscopy allow us to follow cells in living animals as hair cell regeneration occurs. The ability to apply these new methods to the problem of hair cell regeneration is tremendously exciting.
Describe a typical day.
I spend most of my day communicating about scientific ideas and research: meeting with members of my lab that perform the experiments, listening to new ideas to advance our research plan, talking with collaborators, reading and writing. I commute by bike—it gives me a chance to get a little exercise and time to think. Some of my best ideas have come on a bike ride!
Tell us about something that you enjoy doing when you are not in the lab or presenting your research.
I’m a bit of a soccer fan, having been both a coach and relatively untalented player. Two knee injuries are keeping me off the field, but I’ve recently taken a course to become a referee. I currently support our local soccer club, the Seattle Sounders, and Liverpool England (where my mother was born).
How has the collaborative effort helped or furthered your research?
Collaboration is the key to innovation. Although there is a romantic picture of a scientist slaving away in isolation, toiling toward “eureka” moments, science works best with communication and sharing ideas. Working with the HRP consortium has allowed participation in a close network of scientists with a common goal.
The expertise of the consortium has been inspiring. Real progress can come at the interfaces of different perspectives; the whole is more than the sum of the individual parts.
What do you hope for the HRP over the next few years?
I hope in the next year we will have a better understanding of the gene regulatory network that underlies hair cell regeneration in species that can do so. In two years we may know which pieces are missing in mammals. In five years I hope we will be able to introduce these missing pieces back into mammals and induce new hair cell regulation.
What is needed to help make HRP goals happen?
Promoting hair cell regeneration is an incredible challenge and I appreciate the dedication of my colleagues in addressing this problem. The support of HHF has been amazing, but more is needed. Increased funding would allow us to apply more of our time and effort towards the goal of restoring hearing.
Integrative Analysis
Seth Ament, Ph.D. (co-chair), University of Maryland
Ronna Hertzano, M.D., Ph.D. (co-chair), National Institute on Deafness and Other Communication Disorders
Albert Edge, Ph.D., Mass Eye & Ear
Stefan Heller, Ph.D., Stanford University
David Raible, Ph.D., University of Washington
Jennifer Stone, Ph.D., University of Washington
This group will take the lead on data curation and analysis. A dedicated full-time HRP analyst is working across groups to help collect and process data, thereby facilitating a broader analysis of cell states and trajectories across species. The group will start by annotating hair cell types from all species so that anyone in the field can assess what kind of hair cell their regeneration approaches may produce, while also easing identification of common hair cell genes, which will help the Cross-Species Epigenetics group. Analysis of the hair cells produced in mouse organoids will be performed as an example. The Ament lab will leverage their expertise in bioinformatics, while the Hertzano lab will continue to oversee upkeep of gEAR, with a goal of making it even easier for HRP members to post their new data and for others in the community to analyze those data. The Edge lab will take the lead on the development of organoids as a screening platform for the future. The Heller, Hertzano, Raible, and Stone labs will validate markers by in situ hybridization across species, and all working group members will help direct the analysis.