John Brigande, Ph.D.
Member: Hearing Restoration Project
Current Institution: Oregon Hearing Research Center, Oregon Health & Science University
Education: Doctorate, Master’s, and Bachelor of Science degrees from Boston College
What is your area of focus?
Our lab endeavors to define therapies to restore hearing and balance in mice that accurately model human forms of inner ear disease. One of every 1,000 births produces a child with deafness, and about another two children out of 1,000 will be diagnosed with significant hearing loss within the first year of life. Our goal is to develop therapies to restore hearing and balance function at birth, or shortly thereafter.
Why did you decide to get into scientific research? Why hearing research?
Research chose me more than I chose research. I have severe to profound hearing loss of unknown cause and intimately understand the challenges and frustration a hearing impaired person faces while trying to communicate effectively. About 40 percent of the time I fill the gaps in a conversation with what I think I hear. I use adaptive strategies to communicate, including visual cues and assistive listening technologies. But what if we could define biological therapies to restore auditory (and balance) function? Could we get a more natural, effective outcome for patients?
What is the most exciting part of your research?
We are testing the idea that gene or drug therapies to treat hearing loss present at birth may be best initiated as the inner ear is still developing. Since the mammalian inner ear forms in the early embryo and matures during fetal development, we need to figure out ways to introduce genes and drugs through the uterus to the inner ear. The embryonic environment is an underwater world that I will spend my career trying to fully understand.
If you had not become a researcher what would you have done?
I cannot imagine life without the lab. As the character Vizzini says repeatedly in the movie “The Princess Bride,” “Inconceivable!” That’s how I feel about an alternative career to developmental neuroscience: Inconceivable!
What has been a highlight or a memorable moment of your career?
In 2004, eight months after starting my work at the Oregon Hearing Research Center, I rushed into Peter Steyger’s office late one evening and asked him to look at fragments of an embryonic mouse cochlea expressing green fluorescent protein. (Dr. Steyger is a member of HHF’s Council of Scientific Trustees, which he chaired, and also a former HHF board member.) This meant—for the first time—that we were able to genetically manipulate the mouse cochlea in utero using DNA from a jellyfish and electric current. We talked for over an hour about the next steps. I’ll always remember that first green cochlea!
What is the best part of the HRP consortium? How has the collaborative effort furthered your research?
The best part is the community—we are all part of the consortium because we believe that cross discipline collaboration is an important and necessary way to advance hair cell regeneration research. Collaboration is the key to the HRP’s success. For example, my primary role involves establishing mouse model systems to test candidate genes for hair cell regeneration. Before I began my research, I collected group input on what an ideal mouse model system should be. To achieve this goal, I will start with a mouse model generated by Dr. Albert Edge and Dr. Stefan Heller; include another model created by Dr. Ed Rubel that he characterized with Dr. Jenny Stone and colleagues; and then add our expertise with gene transfer to the cochlea. That’s the work of five consortium members on one model system! The collaborative effort enables us to do science that very likely would not be possible alone.
Which scientist or mentor do you find the most inspirational?
Peter Barr-Gillespie, Ph.D., the HRP’s scientific director. He guides the consortium through the nuts and bolts of the work we do and helps us advance the science by challenging our thought processes. He has deftly managed a group of smart, creative, and passionate researchers. I have a great deal of trust in Peter’s guidance, and I find his leadership to be truly inspired by an authentic passion to advance hair cell regeneration research.
What do you hope to have happen with the HRP over the next five years?
Over the next five years, I expect that we will have identified novel candidate genes for hair cell regeneration and that we will have validated these genes in the chick, fish, and mouse model systems. This will then usher in the third phase of the strategic plan: drug discovery based on validated genes and pathways.
What is needed to help make HRP goals happen?
We need more money to support additional research. There are nearly 50 million people in the United States with hearing loss. We—the hearing impaired—are so numerous that we have the critical mass to raise the money needed to more rapidly advance scientific discovery. That’s empowerment at its best! I believe strongly that the work of the HRP will contribute to new and improved treatments for hearing loss and tinnitus.