Research The Latest Research on Hair Cell Regeneration to Restore Hearing. Lauren McGrath

The Latest Research on Hair Cell Regeneration to Restore Hearing

Hearing Health Foundation’s collaborative Hearing Restoration Project consortium headlined a scientific conference in New York City to advance cures for hearing loss. By Lauren McGrath

The New York Academy of Sciences (NYAS) hosted “Hearing Restoration and Hair Cell Regeneration,” a symposium in early October 2019 to connect internationally recognized hearing loss experts from academia, industry, government, and nonprofit organizations. Hearing Health Foundation (HHF) scientists spoke and presented, and HHF also served as a promotional partner for the conference.

Armed with the knowledge that non-mammalian species have the ability to regenerate their inner ear sensory hair cells and restore their hearing, 11 speakers delved into the science during the full-day symposium in New York City. This included two researchers who are funded by HHF through the Hearing Restoration Project (HRP): HRP scientific director Peter Barr-Gillespie, Ph.D., of Oregon Health & Science University, and HRP consortium member Tatjana Piotrowski, Ph.D., of the Stowers Institute for Medical Research in Missouri. NYAS program manager Kari Fischer, Ph.D., and NYAS Scientific Organizing Committee member Michael Franti, Ph.D., introduced the conference, which began with keynote speaker Barr-Gillespie and his presentation, “A Cross-Species Approach to Hair Cell Regeneration.” This presentation was an overview of the HRP’s work investigating the restoration of hearing in humans by converting remaining cells in the inner ear into functional hair cells.

Barr-Gillespie noted that two pivotal papers from the late 1980s, “Regeneration of Sensory Cells After Acoustic Trauma” and “Hair Cell Regeneration After Acoustic Trauma in Coturnix Quail,” which were coauthored by HHF Emerging Research Grants (ERG) scientists Douglas Cotanche, Ph.D., and Edwin Rubel, Ph.D., respectively, added greatly to the knowledge of how hearing works. These HHF-funded discoveries that birds can spontaneously regenerate their hearing once it has been

lost formed the basis of the HRP, established in 2011.

The overarching principle of the HRP, Barr-Gillespie explained, is collaboration through the open sharing of data and ideas. Consortium members use a comparative approach, examining the hearing mechanisms of chickens and zebrafish, which both show robust hair cell regeneration, as well as mice, which do not show hair cell regeneration in the cochlea. Barr-Gillespie provided greater context on several active, species-specific projects led by consortium members.

He noted that HRP members share their data through a portal, the gEAR (gene Expression Analysis Resource), developed by consortium member Ronna Hertzano, M.D., Ph.D., of the University of Maryland Medical Center, which enables analysis and visualization of complex data and resource-sharing among the greater scientific community. Barr-Gillespie posits that furthering our understanding of gene-regulatory networks used to build hair cells and maintain supporting cells will ultimately enable regeneration strategies.

Piotrowski’s presentation, “Hair Cell Regeneration in the Zebrafish Lateral Line,” provided specifics that followed up on Barr-Gillespie’s overall summary of the consortium’s cross-species approach. Zebrafish lateral line cells are homologous to mammalian inner ear hair cells, but they detect water movement instead of sound in order to preserve their ability to orient themselves. Piotrowski’s lab investigates which genes, including transcription factors, guide the regeneration of hair cells and how these genes are regulated by enhancers. Enhancers are DNA sequences in the genome that increase the expression of nearby genes. Identifying the specific enhancers, for example, that are active in zebrafish regeneration provides a better set of candidate targets that could be useful in triggering regeneration in mice.

The NYAS symposium also featured a poster session

HRP scientific director Peter Barr-Gillespie, Ph.D., was the keynote speaker at an October 2019 New York Academy of Sciences conference.

by early career investigators including 2019 ERG scientists Anat Lubetzky, Ph.D., of New York University, presenting her research on balance, and Vijaya Prakash Krishnan Muthaiah, Ph.D., of the University at Buffalo, with his research on blast-induced traumatic brain injury. The inclusion of the poster session served as a welcome reminder that scientific research involves not only formalized collaboration, but also an appreciation that complex biological systems like hearing and balance depends on sharing information more broadly, and that better understanding of the basic science will inform future treatments and cures.

The event provided a fantastic opportunity for senior experts in the field of hearing restoration to survey advances in the field in recent years and to confer— formally in the question-and-answer segments of the program and informally during breaks—on next steps and directions for future research. HHF is particularly proud of the prominence of both the HRP consortium and ERG program at the event. Our donors continue to fund groundbreaking scientific research and support scientists who are leading the way in achieving a core aspect of HHF’s mission: curing hearing loss.

Lauren McGrath is HHF’s director of marketing and communications. For more about the HRP including Barr-Gillespie’s full presentation, “A Cross-Species Approach to Hair Cell Regeneration,” see hhf.org/hrp.

›› ›› Principles of the HRP » International composition (the U.S., Canada, and the U.K.) of 10 to 14 investigators, plus the scientific director » Overarching principle is collaboration: the open sharing of ideas and data » Funds projects not traditionally funded by the National Institutes of Health (such as genome-wide inquiries) » HHF’s Scientific Advisory Board provides oversight and guidance to the HRP consortium Our Reach The work of these HHF-funded researchers was cited by NYAS presenters: research

Kumar Alagramam, Ph.D.; 2002 ERG recipient Ruth Anne Eatock, Ph.D.; 1987–88 and 1994 ERG; member of the HHF Board of Directors John Brigande, Ph.D.; HRP consortium member Albert Edge, Ph.D.; HRP consortium member Andy Groves, Ph.D.; HRP and 1996–97 and 2012 ERG Michelle Hastings, Ph.D.; 2009 and 2011 ERG James Hudspeth, M.D., Ph.D.; 1979–80 ERG Lawrence Lustig, Ph.D.; 2002 ERG (and a presenter at the NYAS conference)

For more, see hhf.org/erg and hhf.org/hrp.

Support our research: hhf.org/donate