Current Institution: University of Southern California
Education: Hampshire College, B.A.; Columbia University, Ph.D.; Rockefeller University, Postdoctoral training
What is your area of focus?
A common cause of deafness is the death of the inner ear’s sensory hair cells. My lab and I research why these cells are not normally regenerated in humans, even though they are rapidly replaced in other animals such as birds and fish.
Our current hypothesis is that the genes needed to regenerate hair cells become restricted or “locked up” during the development of the embryo. My lab is investigating the nature of this “lockup” phenomena, with the goal of stimulating regeneration, and thus hearing, in humans. Powerful new techniques for manipulating the state of a cell’s DNA have become available over the past several years, technology we are using to test our theories.
Why did you decide to get into scientific research?
At Hampshire College in the 1970s the graduation requirement was to spend your final year writing a thesis on a topic of your choice. I hadn’t studied much biology until then but I was interested in questions about life on earth, and this led me to a wonderful developmental biology lab at Smith College, our sister school. With the help of my advisor, I designed a project on regeneration of the lens in the eye of the red-bellied newt, a classic regeneration model that I was able to catch in the local ponds of western Massachusetts. The project was successful, the outcome raised lots of new questions, and my professor encouraged me to write it up and publish it. I think that initial success, and the encouragement I received, was a key factor in my eventual decision to become a scientist.
Why hearing research?
I had completed my Ph.D. in biochemical embryology and gene regulation and decided to do postdoctoral training in a new field, namely cell cycle research and transcriptional control. I was interested in how genes manage to maintain their pattern of expression through repeated cell divisions (mitosis), a phenomenon now known as “mitotic bookmarking.” When I began looking for a faculty position, I serendipitously learned that a new department of Cell Biology was opening at the House Ear Institute in L.A. and that David Lim, Ph.D. (a member for HHF’s Council of Scientific Trustees), was looking for people to join. Jeff Corwin, Ph.D., introduced me to David, and eventually I was persuaded that the inner ear was a great model system for many of the developmental biology questions that interested me.
What is the most exciting part of your research?
In addition to making predictions and designing experiments to test them, the most exciting part is when experiments don’t work the way you think they will, and something unexpected emerges. These days I enjoy the same thing more vicariously. I like hearing new ideas that come from discussions with creative people in my lab—and then pestering them mercilessly until I hear the outcome of the experiments that follow.
Tell us something you enjoy doing when you are not in the lab or presenting your research.
I enjoy hiking in the mountains to the north of L.A., where I live. The mountains are large, rugged, and covered with sage and rosemary. They are also a little dry and dusty, but in the spring—and at least when it rains, as it has this winter—there are great wildflowers. Years ago, fellow HRP member Andy Groves, Ph.D., and I went hiking together every Sunday morning. That was really the genesis of our collaboration that continues today.
What has been a highlight or something valuable you’ve gotten from the HRP consortium collaboration thus far?
The HRP provides an ongoing, supportive forum for me to discuss progress and ideas about how to solve the problems of hair cell regeneration with a group of people in the field whom I admire. These discussions and the critical feedback about our work help both to direct the research and overcome roadblocks.
What do you hope to have happen with the HRP over the next year, two years, five years?
I think the cross-species comparative approach that is embodied by the HRP strategic plan will prove to be even more useful in the near future. My hope is that in the next few years this will yield a description of the gene regulatory networks that are important in hair cell regeneration. From there I hope we can develop drugs or therapies that stimulate hair cell regeneration.
What is needed to help make HRP goals happen?
In a phrase: continued funding. The HRP got the ball rolling by identifying and initially funding projects deemed essential for future progress toward new treatments for hearing loss. However, the experiments needed to reach this goal are labor-intensive and rely on the most sophisticated modern technologies, and so are necessarily expensive. The HRP has provided the impetus vital for this work, and its continued support is crucial to the future of this effort.