Marine Biological Laboratory Names Brian McDermott, PhD, a Whitman Center Research Award Recipient

Innovations in Ear, Nose & Throat | Summer 2023

Named a 2023 Whitman Center Research Award Recipient by the Marine Biological Laboratory (MBL), Brian McDermott, PhD, will spend two months this summer at the prestigious institution in Woods Hole, Massachusetts.

Brian McDermott, PhD

Founded in 1888 and affiliated with the University of Chicago since 2013, MBL is a private, nonprofit research and education hub. Past MBL researchers include 60 Nobel Prize winners, 306 National Academy of Sciences members and 236 American Academy of Arts and Sciences members. As a Whitman Center fellow, Dr. McDermott will receive lab space and housing to advance MBL’s mission of biological discovery, which aligns with his goals at University Hospitals Cleveland Medical Center.

Dr. McDermott is an Associate Professor of Otolaryngology, Genetics and Genome Sciences, and Neuroscience at University Hospitals and Case Western Reserve School of Medicine. He leads a team of researchers utilizing zebrafish models to understand the molecular mechanisms of hair cells — the cellular receptors of sound — and their effects on human hearing and deafness. The McDermott Lab Zebrafish Research Facility is one of only a handful nationwide devoted to the study of hearing, and it houses over 30,000 fish that bear optically clear offspring.

At the MBL, Dr. McDermott will extend his study of hair cells to squid models. Along with offering genome sequencing capabilities, the marine research facility has developed techniques to grow squid via cultures. “Although we have come a long way in advancing our understanding of the genes that cause hearing loss, there is still little known about the molecular biology of invertebrate hair cells,” he says. “Despite serving a similar purpose and having a similar shape, invertebrate hair cells seem quite different in terms of their protein construction.”

Larval zebrafish imaged under normal light conditions.

Larval zebrafish that expresses Green Fluorescent Protein in hair cells.

During his fellowship, Dr. McDermott expects to find fascinating similarities and differences between squid and zebrafish hair cells. “If you want to understand something, look at two markedly different models and identify the characteristics preserved in both,” he says. “Those are potentially the most important structures. On the other hand, it is possible that hair cells from different organisms use entirely different proteins to carry out similar tasks. Either finding could shed light on how hearing works in humans.”

A New Era in Hearing Research

“Zebrafish and humans share the same cells for hearing,” says Dr. McDermott. “Their hair cells look and act the same, and the genes that cause deafness in zebrafish also cause deafness in humans.” Unlike the millions of photoreceptors found in the eyes, humans are born with just 16,000 hair cells. Named for their tuft-like projections that line the cochlea, the cells convert mechanical movement into an electrical response that enables the brain to perceive sound. In humans, hair cells do not regenerate if damaged or destroyed, causing a degree of hearing to be irrevocably lost.

Kumar Alagramam, PhD

“Our hearing research group is interested in understanding why these hair cells are exquisitely sensitive to insult,” says Kumar Alagramam, PhD, the Anthony J. Maniglia Chair for Research and Director of Research and Education in Otolaryngology – Head and Neck Surgery at University Hospitals in collaboration with the School of Medicine. “As we better understand the basic mechanisms, we can begin to investigate therapeutic ways to intervene.” The team is continuously searching for potential mitigations to hearing loss, hypothesizing ways to rescue protein function or replace mutant genes.

“Advances in genomics, including CRISPR-Cas9 genome editing technology, and enhanced imaging capabilities are creating opportunities to better understand the role of genes in various organisms,” says Dr. McDermott. “We will be able to take findings about squid hair cells and make comparisons to our recent discoveries in zebrafish.”

Hair Cells Tuned to the Direction of Water Flow

Recently, Dr. McDermott published research in the journal Current Biology, along with Ruben Stephanyan, PhD, Assistant Professor of Otolaryngology – Head and Neck Surgery at the School of Medicine, and Katie Kindt, PhD, Chief of the Section on Sensory Cell Development and Function at the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health.

“We were investigating a group of TMC [transmembrane channel-like] proteins in zebrafish, which are ion channel proteins that hair cells of mice use to detect sound,” says Dr. McDermott. “Zebrafish have a particular advantage over other model systems in that they have hair cells on their surface that give them a superhero power to sense water movement and the direction of water flow.” The team discovered that zebrafish use different TMC proteins to sense the directionality of water movement, making them more sensitive to water that comes from behind — perhaps from predatory animals. The genes that encode the TMC proteins are also involved in hearing and deafness in humans. “Our findings demonstrate that the genes involved in hearing and deafness play a role in detecting water movement in zebrafish,” he adds.

Dr. McDermott credits Nicole Maronian, MD, Chair of the UH Department of Otolaryngology – Head and Neck Surgery and the Julius W. McCall Professor at the School of Medicine, for her support of this larger vision of studying zebrafish and the genetic underpinnings of human hearing and deafness. Recently, Dr. Maronian and fellow leaders at University Hospitals secured philanthropic funds to upgrade the fish facility so that researchers can continue their innovative work.“The advantage of collaborating in an academic medical environment is that we are constantly surrounded by the people who are the purpose behind our research,” says Dr. McDermott. “Improving or restoring hearing for children and adults is our ultimate goal.”

For more information, contact Dr. McDermott at bmm30@case.edu.

Contributing Experts:
Brian M. McDermott, Jr., PhD
Department of Otolaryngology–Head and Neck Surgery
University Hospitals Cleveland Medical Center
Associate Professor
Case Western Reserve University School of Medicine

Kumar Alagramam, PhD
Department of Otolaryngology–Head and Neck Surgery
University Hospitals Cleveland Medical Center
Anthony J. Maniglia Chair for Research
Director of Research and Education
Professor
Case Western Reserve University School of Medicine