Mark Warchol, Ph.D.

Member: Hearing Restoration Project
Current Institution: Washington University in St. Louis
Education: B.S. degree from the University of Washington; Ph.D. from Northwestern University; postdoctoral work at the University of Virginia

The Warchol Lab

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What is your area of focus?
My lab currently has two research foci. First, we’re trying to understand the process of regeneration in the avian ear. Like humans, birds are warm-blooded vertebrates, and their inner ears function in similar ways. However, the avian ear also has an amazing ability to regenerate after injury. Understanding the molecular signals and pathways that underlie this reparative process will suggest ways for inducing similar forms of regeneration in humans.

In a related line of work, we are looking into the possible role of innate immune cells (macrophages) in promoting sensory regeneration. Immune cells enhance repair and regeneration in other tissues of the body, and injury to the inner ear leads to activation and recruitment of these cells. Still, it is not clear whether these cells can help stimulate regeneration in the cochlea. Our current data suggest that immune cells are important for the survival of auditory neurons after cochlear injury. Since these neurons convey information on sound from the ear to the brain, they are critical to the performance of cochlear implants.

Why did you decide to get into scientific research? Why hearing research?
I have always been drawn to science and never really considered doing anything else.
Understanding and explaining things—especially complex things like the inner ear and the
nervous system—is really satisfying. As far as my interest in hearing research, it occurred by accident. I became interested in neurobiology while I was an undergraduate. I was fortunate to spend a couple of years working as a research technician at Oregon Health & Science University, where I learned a
number of methods for recording electrical signals from the auditory system. That era, the early 1980s, was a very exciting time in hearing research. New phenomena, like otoacoustic emissions and active amplification in the cochlea, were first being described and debated. I quickly became fascinated with the operation of the cochlea and have been doing research on the inner ear ever since.

What is the most exciting part of your research?
Any new data are exciting, particularly when they run counter to my own expectations! I am also interested in the comparative biology of hearing. All animals that hear confront a common problem: how to detect a wide range of sound intensities and also achieve fine discrimination of both pitch and timing. The vertebrate ear has evolved a number of different ways to achieve this goal. The ancestors of birds and mammals diverged about 300 million years ago, and their ears possess some interesting and unique specializations.

In collaboration with fellow HRP researcher Michael Lovett, Ph.D., we have compiled extensive genomic data on the avian cochlea and vestibular organs. These studiesshould provide insights on regeneration, but I am also hopeful that they will help us to better understand the processes of divergence and convergence during the evolution of the avian and mammalian ear.

What do you enjoy doing when you’re not in the lab?
Outside the lab, I still do a lot of science-y stuff. I enjoy astronomy, and also visiting zoos and watching nonhuman primates. I like museums of art and natural history, and I always look forward to the several weeks each summer I spend with my family in rural Maine.

How has the collaborative effort helped your research?
Much of my work with the HRP has focused on characterizing gene expression in the regenerating chick cochlea and utricle. By identifying all of the genes that are involved, we hope to construct a roadmap that will guide similar regenerative efforts in humans. This has been a true collaborative effort, involving scientists at Imperial College London as well as Stanford University and the University of Washington. Hearing Health Foundation has funded this work and has been valuable in facilitating this collaboration.

What has been something valuable you’ve gotten from the HRP consortium collaboration thus far?
In addition to this project collaboration, I also find the semiannual HRP meetings to be very beneficial. At least twice a year, we all meet in person to discuss our latest findings and to formulate plans for future research. Having a large group of experts all in the same room and focused on a common problem is a great way to make progress.

What do you hope for the HRP over the next few years?
The long-term goal of the HRP is to develop methods for repairing the inner ear and restoring hearing. We can approach this in a couple of ways. First, we can experiment with the injured mammalian ear, using methods like gene therapy or treatment with novel drug compounds to attempt to induce regeneration. Second, we can find out exactly how regeneration occurs in animals whose ears are able to regenerate spontaneously (fish and birds). Progress is most likely if we pursue both approaches simultaneously. I am particularly hopeful that HHF–supported research will allow us to identify the specific genes and signaling pathways that lead to sensory regeneration in the avian ear.
While there is no doubt that HHF and its generous donors have been very supportive of the HRP consortium, increased funding will lead to greater research and accelerated discovery toward a cure. Your support can help us achieve our goal, faster.

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Research