Current Institution: Harvard Medical School
Education: SUNY Albany, B.S.; Medical College, Ph.D.; Harvard Medical School, Postdoctoral Fellowship
What is your area of focus?
When mammalian hair cells are damaged or die, the result is permanent hearing loss. My lab’s goal has been to make new hair cells in the damaged cochlea, starting from cells that remain in the cochlea after damage. We are studying cells in the ear that may be made to differentiate into (turned into) new hair cells by manipulating cell signaling pathways.
Why hearing research?
I am interested in understanding the controls on cell fate and how cells communicate and perform their functions. My graduate and postdoctoral work in the biochemistry and molecular biology of cellular interactions led to an interest in the pathways controlling the differentiation of stem cells into neurons and the use of stem cells for the replacement of neurons in the central nervous system. For me the ear was a perfect model system for the study of cell fate (what cells turn into), as we can measure the consequences of circuit replacement and synapse replacement at both the cellular and whole-organism level.
What do you hope to achieve with your current research?
It is our hope that our research on hair cell regeneration in animal models leads to drug therapies for humans with hair cell loss in the cochlea. Although adult mammalian hair cells do not regenerate, birds and lower vertebrates can regenerate hair cells. Most significantly, we also found that newborn mice can regenerate hair cells after damage.
We are able to use the newborn mouse model to study the specific genes and molecular mechanisms that are important for cell regeneration after damage. Our lab recently found that a series of genes in the Wnt pathway are important for spontaneous regeneration in the newborn mouse cochlea. As the mouse ages, these pathways are attenuated to prevent unwanted cell division. These important checks and balances, however, may be a hindrance for regeneration. Inhibitors of this process of checks and balances may be targets for drugs and may spur hair cell regeneration in mammals that would otherwise be silenced.
Tell us about something you that enjoy doing when you are not in the lab or presenting your research.
I’ve been fortunate to have many trainees from across the globe work in my lab. It’s been a pleasure to get to know the graduate students and postdoctoral fellows from around the world as well as to work alongside these scientists. After these postdoctoral fellows have gone back to their home universities I have also been invited to visit their institutions and present my research, and this has led to international collaborations that help to advance the science.
Thanks to my international ties, I was invited to become a visiting professor at Keio University in Japan. This was an honor; I now spend several weeks each year in Japan giving lectures and working with several former fellows in Tokyo who have since become established researchers. This has been a great experience and opportunity because I’ve benefitted greatly from the collaborations with the scientists, as well as been able to immerse myself in their culture and travel around Japan.
What has been a highlight or something valuable you’ve gotten from the HRP consortium collaboration thus far?
Before the HRP, a lot of basic information needed for designing therapies was unknown. This is in part due to the preference of grant committees for interesting hypotheses rather than the cataloguing of basic information. Much of that information—on gene expression in cochlear cells, effects of damage, cells that could serve as a source of new hair cells—is now available to the research community from data generated by the consortium, which I believe will bring great innovation to the field.
How has the collaborative effort helped or furthered your research?
The consortium’s work has provided a wealth of information. The main focus of the HRP is assessing the single cell effects of hair cell loss as well as the activity of genes in single cells during the regeneration process. This can be studied in birds and fish, as well as in newborn mouse models, where regeneration occurs spontaneously. Thanks to the work done in the consortium, we know that supporting cells survive hair cell loss and we are targeting these cells in our ongoing work.
What do you hope for the HRP over the next few years?
The HRP’s focus is to study pathways that may be able to be targeted for the regeneration of hair cells. In the next few years, I hope we are able to answer questions about hair cell regeneration system such as: What genes are of key importance for spurring regeneration? What genes/pathways can be inhibited? What cells remain after damage? What epigenetic factors control the fate of supporting cells? More funds are needed to find and uncover the answer to these questions, and others that will naturally arise. With HHF’s continued support and the generosity of its donors, the HRP can hopefully expand its research efforts to achieve our shared goal of developing drugs to treat and cure hearing loss.
Peter Barr-Gillespie, Ph.D.
Seth Ament, Ph.D.
John Brigande, Ph.D.
Alain Dabdoub, Ph.D.
Albert Edge, Ph.D.
Andy Groves, Ph.D.
Stefan Heller, Ph.D.
Ronna Hertzano, M.D., Ph.D.
Michael Lovett, Ph.D.
Tatjana Piotrowski, Ph.D.
David Raible, Ph.D.
Yehoash Raphael, Ph.D.
Neil Segil, Ph.D.
Jennifer S. Stone, Ph.D.
Mark Warchol, Ph.D.