Philippe Vincent, PhD

Primary Academic Title

Assistant Professor of Otolaryngology-Head and Neck Surgery

Background

Centers and Institutes

Center of Hearing and Balance

CV

https://www.hopkinsmedicine.org/-/media/profiles-support/cvs/vincent.pdf

LinkedIn

https://www.linkedin.com/in/philippe-vincent-587758a5/

Research Interests

Hearing, Neurosciences, Hair cells, Ribbon synapses, Synaptic transmission, Synaptic Transmission, Synapse Regeneration and Repair, Olivocochlear efferent system

Research Summary

Besides genetic disorders, ototoxic drugs (e.g., aminoglycosides, cisplatin), noise exposure and aging often lead to sensorineural hearing loss due to damage of sensory hair cells and/or auditory nerve fibers (ANFs). In mammals, there is very limited spontaneous repair; therefore, cumulative damage in the inner ear, like repetitive exposures to loud noise, will ultimately cause various degrees of hearing loss. People with hearing loss are at a greater risk for social isolation but also for depression and dementia. According to the world health organization, about 17% of teenagers and 19% of young adults in their 20’s already present signs of noise-induced hearing loss, this mainly caused by listening to loud music but also due to the increasing noise pollution in general, like road traffic, roadworks, etc. Those numbers will likely increase in the upcoming decades, highlighting the importance for understanding the underlying mechanisms that limit both hair cell and ribbon synapse regeneration and for trying to find strategies to either protect ribbon synapse from damage and/or induce and improve hair cell and synapse regeneration.

Sound is encoded by ribbon synapses between cochlear inner hair cells (IHCs) and type-I ANFs in the inner ear. Each IHC is contacted by 10 to 20 type-I ANFs, each of them receiving inputs from a single presynaptic ribbon. IHC/type-I ANF synaptic transmission is known to be fast, reliable, and indefatigable; those properties are important for faithful and sustained sound encoding throughout our entire life. In addition to those properties, ANFs display their own encoding features. In vivo single unit recordings performed from type-I ANFs in the cat showed that those fibers have different spontaneous firing rates, activation thresholds and dynamic ranges in response to increasing sound intensities1 that correlate with their contact position (modiolar vs pillar) on the IHCs. These properties also were found in rats, mice, and other mammalian species. However, the underlying molecular mechanisms that set and regulate IHC/type-I ANF synaptic transmission are still largely unknown although several hypotheses have been proposed. The lateral olivocochlear (LOC) efferent fibers directly contact the unmyelinated part of type-I ANFs below IHCs. Little is known about the role of the LOC system in the inner ear although it has been proposed to regulate the spiking rate of the type-I ANFs and protect against noise trauma. So, investigating how the LOC system regulates the IHC/type-I ANF synaptic transmission is important not only for our basic understanding about sound encoding but also will help us to uncover mechanisms that could protect against synaptopathy, an important consequence of noise-induced hearing loss. My research focuses on revealing fundamental molecular mechanisms that are involved in the setting of the IHC/type-I ANF synaptic transmission properties, especially interrogating the dual role of the LOC efferent system in modulating afferent activity, and protecting ribbon synapses from noise damage.

Moreover, progress has been made towards hair cell and ribbon synapse repair after trauma, but so far, there is no effective treatment available for patients besides prevention of damage or devices such as hearing aids or cochlear implants. Therefore, in addition to research onto protecting ribbon synapses from damage. I perform research on hair cell and ribbon synapse repair by assessing and improving the function of newly formed hair cells and newly formed ribbon synapses. This work will inform the development of regenerative therapeutics to cure hearing loss.

Google Scholar - Publications

https://scholar.google.com/citations?user=MnoQpmcAAAAJ&hl=en

PubMed - Publications

https://www.ncbi.nlm.nih.gov/myncbi/1Z75thkuVR_kl/bibliography/public/

Research Gate - Research Profile

https://www.researchgate.net/profile/Philippe-Vincent-10

Selected Publications

• Vincent PFY, Young ED, Edge ASB, Glowatzki E. Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro. Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2315599121. doi: 10.1073/pnas.2315599121. Epub 2024 Jul 26. PMID: 39058581; PMCID: PMC11294990.
• Siebald C, Vincent PFY, Bottom RT, Sun S, Reijntjes DOJ, Manca M, Glowatzki E, Müller U. Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties. Proc Natl Acad Sci U S A. 2023 Aug;120(31):e2217033120. doi: 10.1073/pnas.2217033120. Epub 2023 Jul 24. PMID: 37487063; PMCID: PMC10400978.