Interviewer: Matthew Lee

Dr. Gabriel Corfas received an M.Sc. in biological sciences from the University of Buenos Aires, Argentina, and a Ph.D. in neurobiology from the Weizmann Institute of Science in Israel. He did postdoctoral training in the laboratory of Dr. Gerald Fischbach, first at Washington University and then at Harvard Medical School (HMS). He then joined the HMS faculty and established his independent laboratory at Boston Children’s Hospital. Before joining the faculty of the University of Michigan and becoming the director of the Kresge Hearing Research Institute, he was a professor in the departments of neurology and otology & laryngology at HMS and director of basic research in otolaryngology at Boston Children’s Hospital.

Matthew: Could you tell me a bit about your current research projects in the Corfas Laboratory? 

We have quite a variety of ongoing projects in the Corfas Laboratory, but all of them are centered around the main theme of exploring the role of glia and neuron-glia interactions in the development, plasticity, degeneration, and repair of the nervous system. 

For example, we discovered that the supporting cells that surround the hair cells of the cochlea and the vestibular sensory epithelia are glial cells, and that they are critical in promoting the formation of synapses and the survival of inner ear sensory neurons. We also discovered the molecules that drive this process and showed that manipulating the level of the expression of these molecules we can increase the number of cochlear synapses and improve hearing. Furthermore, we can also regenerate synapses after noise exposure and restore hearing. Most exciting is our recent finding that with this same approach we’ve been able to slow down the process of hearing loss with aging.

Another project focuses on the plasticity of the myelinating cells. Many of the axons in the nervous system are covered by myelin, which is produced by glia, oligodendrocytes in the central nervous system, Schwann cells in the peripheral nervous systems. We’ve been interested in determining if these cells are influenced by experience. For example, we’ve discovered that social isolation dramatically impedes the maturation of oligodendrocytes in the prefrontal cortex, a key part of the brain that is important for social interactions, working memory, and psychiatric health. 

In another project we’re trying to determine if the myelinating cells in the peripheral nervous system (Schwann cells) are also influenced by experience. We chose to do this by looking at the auditory system, where it is easy for us to manipulate the activity of the auditory neurons. Other nerves in the periphery are more complex, with some axons being specific for motor function, and sensory axons mediating diverse types of sensory modalities, making it hard to alter just one specific experience. We are using genetically modified mice and sound enrichment or deprivation and measuring what happens to the function and structure of the inner ear. 

Matthew: What drew you to these topics of research, in particular, the mechanisms of hearing, and why? 

I started my career being fascinated with behavior and trying to understand how experience changes the brain, and how those changes to the brain affect behavior. For my PhD I used a combination of genetics, anatomy, physiology, and behavior, to study those questions in fruit flies. Then, for my postdoctoral training, I wanted to get more insights into synaptic physiology and the molecular biology of the synapse, so I went to a lab that was studying the development of the neuromuscular junction. There, I learned how to do cellular and molecular biology. That taught me the power of the molecular approach, we were able to identify a key factor that was regulating the synapse formation.

Then I started my own lab, and I decided to focus on how neural-glial interactions mediate the development of the cerebellum. We hypothesized that disrupting a particular molecular pathway that mediates communication between neurons and glial would result in mice with cerebellum developmental defects. The mouse had the expected dysfunction, it had balance problems, but surprisingly had no cerebellar defects. We reasoned that the alternative was a problem in the inner ear. Indeed, we found that by chance, our genetic manipulation altered glia in the inner ear instead of the cerebellum. Luckily, this led us to discover that these cells that nobody had paid attention to, the supporting cells, were glia and were able to play very important roles. I saw that as a very fertile and open field that nobody was looking at, that could have a remarkable impact on how we think about the inner ear and hearing and balance. And I thought, well somebody has to do this, and now it is exactly what I am doing 20 years later. I was lucky to have great collaborators and we were able to change the field, just because of a mouse. It was just following the science, following the observations, and being able to assess that it was an important question and we had now a way of addressing something that nobody had thought about yet. 

Matthew: What are some of the fundamental lab techniques you train undergrads to use in your lab? Do you have a favorite lab technique? What does a typical day in the lab look like? 

Generally, when undergrads come into our lab, they have a chance to try many different techniques. Undergrads start working with a grad student or a postdoc, and depending on the project, they start learning one technique. Then, once they gain skills and confidence, we allow them to grow expertise in others. We have had students that have done auditory physiology, histology of the inner ear, histology of the brain, behavior of mice, molecular biology, quantitative PCR, mouse handling, mouse dissection, biochemistry, tissue culture, Western blots, fluorescence confocal microscopy. There are many techniques for students to train in, all depending on the project and the passion of the student, and their willingness to try. 

Matthew: As the director of the Kresge Hearing Institute here at U-M, what are some of the goals you want the institution to reach, and how do you plan to achieve them? 

The mission of the Kresge Hearing Institute is to define and understand the basis of auditory and vestibular health, and to use that knowledge to understand the basis of disease, and translate that knowledge to developing new therapies. The way we approach that is to have different labs that use different techniques to address different questions, from basic to translational and human subject-based research.

By being all together and helping each other, we are able to improve the chances that we will be able to do great basic science, and develop translational medicine that can help patients. For example, now that we know how to slow down age-related hearing loss, we hope we will be able to help in the development of drugs that would be helpful for people like me. 

Matthew: What are some of the potential applications of your research, and what are some of the ways you wish to elaborate on your current findings? 

We have two projects that are drug-development oriented, which include developing drugs to treat auditory neuropathy and peripheral neuropathy. In that case, we have discovered the key molecular pathways important to those processes, and we are using molecules to treat these neuropathies. We hope that we can use our research to help treat other neurodegenerative diseases. 

Matthew: What are some of the current obstacles and/or limitations that your research currently faces? 

I think that what it really is, is our ability to garner all the resources we need at the right time and at the right place. Sometimes, it's a real challenge to bring other people together for a multidisciplinary approach. I feel like we could do better, be faster, and what that means is basically, we need more resources. We need more money, more equipment, and we are all ambitious and sometimes we feel that things move at a slow pace. But that’s the reality of science. It takes time. 

Matthew: What was your experience starting out in the field of research, and what advice would you give to undergraduates looking to get involved in research? 

In my opinion, there is nothing more exciting, rewarding and fulfilling than doing research. You have a life of playing and learning. It is challenging, in research, you should expect to spend a large percent of your time failing. And you need passion, because research isn’t an easy career. It is hard work, it requires time, patience, and training. For example, for my PhD, I needed to learn how to label single neurons in a fly to study how “memory mutations” change their anatomy. I had to go to a lab in Switzerland to learn to do it, it took me more than a month of failure to finally get it. It then took me another year and a half to get the experimental results and be able to publish a paper. You have to be cautious and understand that failure is part of the process. And not everybody appreciates that. You have to learn to enjoy the failures first to enjoy the discovery. 

Matthew: What kinds of students do you work with on a regular basis? What has been your experience as a faculty mentor for the Neuroscience Graduate Program?

I have both undergraduate and graduate students in my lab, and I also participate in the thesis advisory committee of a number of graduate students in other labs. I enjoy seeing my students grow into scientists. When we start, we are all naive. I was incredibly naive when I entered graduate school, and a certain degree of naivete is good because it lets you think about things that nobody else thought about or had the willingness to try, and then seeing them end up being effective scientists is great. 

Matthew: Was there a faculty member or mentor who inspired you to pursue research or helped you along the way?

I would not be here if it wasn’t for so many people. It started in Argentina for my undergraduate thesis in a lab studying fungi. It was a different time and place, with much less resources, but the people there were all very smart and resourceful. I saw people devoting their lives to science, and it was inspiring. When I went to my PhD in Israel, I was lucky to have a very smart advisor that, while knowing very little about my lab techniques, could still teach me how to design experiments, analyze data and communicate my findings. My postdoctoral mentor at Harvard taught me how to look at the bigger picture, how to lead, and gave me the freedom to try and explore new techniques and fields. The chair of my department at Boston Children’s Hospital was also a great mentor from whom I learnt a lot about how to run an effective lab, and lead a department. And my long term collaborator and friend at Massachusetts Eye and Ear Infirmary, who introduced me to hearing science. These are some of the key people that helped shape me and my career.

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