Publications

Anthony J. Ricci, PhD
Anthony J. Ricci, PhD
Edward C. and Amy H. Sewall Professor in the School of Medicine and Professor of Otolaryngology - Head & Neck Surgery (OHNS) and, by courtesy of Molecular and Cellular Physiology

Bio

I was born in the Bronx, NYC, nearby Yankee stadium. As a kid education was not a priority more of a distraction. Fortunately, my grandmother pushed me to go to college and to go away to college. As the first family member to leave NYC as well as to attend college it was really eye opening. At Case Western Reserve in Cleveland, I majored in Chemistry, with minors in Biology, Sociology and Biomedical Engineering. It was here through a work study job that I was introduced to research and found that there were real life applications to the textbook learning. I was fortunately to work in the lab of a PI who saw potential in me and helped direct me toward graduate school. I was also fortunate to work in an upward bound program where I realized I enjoyed teaching and working toward giving others opportunities academically. I was the first graduate of a new neuroscience PhD program at Tulane University. It was here, aside from falling in love with New Orleans, that I found my niche working in sensory neuroscience at the cell and molecular level. Following graduate school, I bounced to the University of Texas Medical Branch at Galveston where I dabbled with imaging technology and moving. Having largely failed in my major research project, I moved to Madison WI, intent on developing new technologies that would allow me to answer the questions for which I was most interested. It was here where I was successful and leveraged technical knowledge and newly developed tools to work on mechanotransduction in auditory sensory hair cells. I launched an independent research career, with a first faculty position back in New Orleans at LSU Medical Center. Hurricane Katrina washed us out to the West coast, where I became part of a new Otolaryngology department with a mission built around optimizing healthcare, building a strong research footprint and educating the next generation of surgeons and scientists. Since joining Stanford, my research interest have expanded to include translational work as well as investigating at the systems level, the role of hearing loss on cognitive function. I have also had the opportunity to engage in teaching and in building programs that expand the population of students who have the chance to reach their scientific potential. These programs enrich our community and help to shape what academia will be in the future. I served as the director of the Neuroscience Graduate Program for about eight years. I was a co-founder of the ADVANCE Summer Institute, an onboarding program for incoming bioscience graduate students from underserved backgrounds. I was the faculty lead for this program for more than 10 years. I was part of the group that created the Bioscience Diversity Advisory Committee, that contributes to ensuring best practices in admissions and recruitment were available to all graduate programs. I was part of the team that built Propel, a postdoctoral fellows program that works to help transition postdocs to faculty positions. Most recently, I helped to create a new postbaccalaureate program as part of the REACH initiative. This program provides a strong research-based opportunity to scholars from underrepresented backgrounds interested in a research or medical career.

Publications

  • Auditory Hair Cell Mechanotransduction Channels Dynamically Shape the Mechanical Properties of Their Membrane Environment. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Sam George, S., Ricci, A. J. 2025: e08268

    Abstract

    The plasma membrane is actively regulated by lipid transporters that create electrochemical gradients between leaflets, and passively by scramblases that dissipate these gradients. Membrane properties such as lipid packing are critical for the proper function of transmembrane proteins, particularly mechanosensitive ion channels. Mechanosensation is a key component of many sensory processes including balance, and hearing. Inner ear hair cells convert mechanical deflection of their hair bundles into electrical signals by gating mechanoelectrical transduction (MET) channels. Transmembrane channel-like proteins (TMCs) are an essential component of the hair cell MET complex, and part of a superfamily of molecules whose members are ion channels and/or lipid scramblases. TMCs are implicated as scramblases in hair cells, however no direct evidence separates scramblase activity from channel properties, nor is there clarity around how MET activity impacts the stereocilia environment. Here, using a novel viscosity sensor boron-dipyrromethene (BODIPY) 1c, this work probes stereocilia membrane viscosity and its relationship with TMC expression and MET current. Using developmental, genetic, electrophysiological and pharmacological tools, this work demonstrates that the MET complex directly regulates the stereocilia membrane viscosity. This work shows that phosphatidylserine externalization does not completely describe, nor solely represent TMC scramblase activity. Lipid flippase/floppase activity along with an MET independent scramblase are implicated in lipid remodeling. Together these data identify a dynamic regulation of stereocilia membrane hypothesized to modulate mechanotransduction channel properties.

    View details for DOI 10.1002/advs.202508268

    View details for PubMedID 40908646

  • Infrared light stimulates the cochlea through a mechanical displacement detected and amplified by hair cells. Proceedings of the National Academy of Sciences of the United States of America Azimzadeh, J. B., Quiñones, P. M., Oghalai, J. S., Ricci, A. J. 2025; 122 (17): e2422076122

    Abstract

    Although cochlear implants (CI) are the standard of care for profound sensorineural hearing loss they are technically constrained by the tendency of electrical current to spread within the fluid-filled chambers of the cochlea. This limits the resolution of individual electrodes and patients' perceptions of complex sounds. Infrared irradiation has been proposed as an alternative to electrical stimulation because it can elicit auditory responses while being spatially constrained, theoretically promising higher-fidelity hearing for the deaf. However, conflicting reports locate the site of infrared excitation at spiral ganglia neurons or hair cells. We use a combination of genetic, pharmacological, optical, and electrophysiological tools to determine the site of action of infrared irradiation. Infrared-evoked cochlear potentials are composed of two peaks: one driven by hair cells (the microphonic) and a second driven by spiral ganglion neurons (the neural response). Manipulations that prevented hair cell synaptic activity abolished the neural component, while manipulations blocking hair cell mechanotransduction abolished all responses, suggesting a mechanical component to the infrared response. Optical coherence tomography (OCT) confirmed that infrared irradiation creates a mechanical stimulus that is both amplified and detected by hair cells. Because infrared irradiation does not stimulate spiral ganglion neurons directly, it is unlikely to replace the electrical CI.

    View details for DOI 10.1073/pnas.2422076122

    View details for PubMedID 40273108

  • The auditory hair cell mechanotransduction complex dynamically regulates stereocilia membrane mechanics George, S., Ricci, A. J. CELL PRESS. 2025: 179A-180A

    View details for Web of Science ID 001547074100125

  • Cochlear Mechanics Are Preserved After Inner Ear Delivery of Gold Nanoparticles. International journal of molecular sciences Pan, D. W., Kim, J., Quiñones, P. M., Ricci, A. J., Applegate, B. E., Oghalai, J. S. 2024; 26 (1)

    Abstract

    Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. We performed optical coherence tomography (OCT) imaging to monitor PSCC infusion of gold NPs into the cochlear chambers. OCT imaging demonstrated that the infusion specifically targeted the perilymphatic spaces within the cochlea. We assessed cochlear mechanics by using OCT vibrometry to measure sound-evoked movements of the basilar membrane. We found no changes in cochlear mechanics between measurements at baseline, after the PSCC canalostomy, immediately after the infusion, and 1 h after the infusion of gold NPs (p > 0.05, paired t-test). These findings validate the PSCC infusion approach for perfusing the cochlear perilymphatic space with a nanoparticle delivery system. Thus, PSCC infusion of nanoparticles is a feasible therapeutic delivery technique for treating inner ear disorders while preserving residual cochlear function.

    View details for DOI 10.3390/ijms26010126

    View details for PubMedID 39795984

    View details for PubMedCentralID PMC11720183

  • Semicircular canal drug delivery safely targets the inner ear perilymphatic space. JCI insight Kim, J., Maldonado, J., Pan, D. W., Quiñones, P. M., Zenteno, S., Oghalai, J. S., Ricci, A. J. 2024; 9 (21)

    Abstract

    Effective, reproducible, and safe delivery of therapeutics into the inner ear is required for the prevention and treatment of hearing loss. A commonly used delivery method is via the posterior semicircular canal (PSCC); however, its specific targeting within the cochlea remains unclear, impacting precision and reproducibility. To assess safety and target specificity, we conducted in vivo recordings of the pharmacological manipulations delivered through the PSCC. Measurements of auditory brainstem response (ABR), vibrometry, and vestibular behavioral and sensory-evoked potential (VsEP) revealed preserved hearing and vestibular functions after artificial perilymph injections. Injection of curare, a mechanoelectrical transducer (MET) channel blocker that affects hearing when in the endolymph, had no effect on ABR or VsEP thresholds. Conversely, injection of CNQX, an AMPA receptor blocker, or lidocaine, a Na+ channel blocker, which affects hearing when in the perilymph, significantly increased both thresholds, indicating that PSCC injections selectively target the perilymphatic space. In vivo tracking of gold nanoparticles confirmed their exclusive distribution in the perilymph during PSCC injection, supporting the pharmacological finding. Together, PSCC injection is a safe method for inner ear delivery, specifically targeting the perilymphatic space. Our findings will allow for precise delivery of therapeutics within the inner ear for therapeutic and research purposes.

    View details for DOI 10.1172/jci.insight.173052

    View details for PubMedID 39513368

  • Large-scale annotated dataset for cochlear hair cell detection and classification. Scientific data Buswinka, C. J., Rosenberg, D. B., Simikyan, R. G., Osgood, R. T., Fernandez, K., Nitta, H., Hayashi, Y., Liberman, L. W., Nguyen, E., Yildiz, E., Kim, J., Jarysta, A., Renauld, J., Wesson, E., Wang, H., Thapa, P., Bordiga, P., McMurtry, N., Llamas, J., Kitcher, S. R., López-Porras, A. I., Cui, R., Behnammanesh, G., Bird, J. E., Ballesteros, A., Vélez-Ortega, A. C., Edge, A. S., Deans, M. R., Gnedeva, K., Shrestha, B. R., Manor, U., Zhao, B., Ricci, A. J., Tarchini, B., Basch, M. L., Stepanyan, R., Landegger, L. D., Rutherford, M. A., Liberman, M. C., Walters, B. J., Kros, C. J., Richardson, G. P., Cunningham, L. L., Indzhykulian, A. A. 2024; 11 (1): 416

    Abstract

    Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

    View details for DOI 10.1038/s41597-024-03218-y

    View details for PubMedID 38653806

    View details for PubMedCentralID PMC11039649

  • Lipid bilayer regulation of cochlear hair cells involves transmembrane channel-like proteins George, S., Ricci, A. J. CELL PRESS. 2024: 506A

    View details for Web of Science ID 001194120702857

  • The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo. Nature methods Yu, C. H., Yu, Y., Adsit, L. M., Chang, J. T., Barchini, J., Moberly, A. H., Benisty, H., Kim, J., Young, B. K., Heng, K., Farinella, D. M., Leikvoll, A., Pavan, R., Vistein, R., Nanfito, B. R., Hildebrand, D. G., Otero-Coronel, S., Vaziri, A., Goldberg, J. L., Ricci, A. J., Fitzpatrick, D., Cardin, J. A., Higley, M. J., Smith, G. B., Kara, P., Nielsen, K. J., Smith, I. T., Smith, S. L. 2023

    Abstract

    Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm2 field of view with submicrometer lateral resolution and is compatible with commonly used multiphoton imaging systems. A novel mechanical design, wider than typical microscope objectives, enabled this combination of specifications. We share the full optical prescription, and report performance including in vivo two-photon and three-photon imaging in an array of species and preparations, including nonhuman primates. The Cousa objective can enable a range of experiments in neuroscience and beyond.

    View details for DOI 10.1038/s41592-023-02098-1

    View details for PubMedID 38129618

    View details for PubMedCentralID 8211867

  • GIPC3 couples to MYO6 and PDZ domain proteins and shapes the hair cell apical region. Journal of cell science Chatterjee, P., Morgan, C. P., Krey, J. F., Benson, C., Goldsmith, J., Bateschell, M., Ricci, A. J., Barr-Gillespie, P. G. 2023

    Abstract

    GIPC3 has been implicated in auditory function. Initially localized to the cytoplasm of inner and outer hair cells of the cochlea, GIPC3 increasingly concentrated in cuticular plates and at cell junctions during postnatal development. Early postnatal Gipc3KO/KO mice had mostly normal mechanotransduction currents, but had no auditory brainstem response at one month of age. Cuticular plates of Gipc3KO/KO hair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted in Gipc3KO/KO cochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks, and the cuticular plate. Several of immunoprecipitated proteins contained GIPC-family consensus PDZ binding motifs (PBMs), including MYO18A, which binds directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell-junction proteins to shape the cuticular plate. (180 words; 180 maximum).

    View details for DOI 10.1242/jcs.261100

    View details for PubMedID 37096733

  • Cholesterol as a tool to probe the role of membrane in cochlear hair cell mechanotransduction George, S., Effertz, T., Ricci, A. J. CELL PRESS. 2023: 91A-92A

    View details for Web of Science ID 000989629700456

  • Tmc regulates membrane viscosity in mammalian cochlear hair cells. Biophysical journal Sam George, S., El Bahloul-Jaziri, A., Ricci, A. J. 2023; 122 (3S1): 91a

    View details for DOI 10.1016/j.bpj.2022.11.692

    View details for PubMedID 36785083

  • Coupling between the stereocilia of rat sensory inner-hair-cell hair bundles is weak, shaping their sensitivity to stimulation. The Journal of neuroscience : the official journal of the Society for Neuroscience Scharr, A. L., Maoileidigh, D. O., Ricci, A. J. 2023

    Abstract

    The hair bundle is the universal mechanosensory organelle of auditory, vestibular, and lateral-line systems. A bundle comprises mechanically coupled stereocilia, whose displacements in response to stimulation activate a receptor current. The similarity of stereociliary displacements within a bundle regulates fundamental properties of the receptor current like its speed, magnitude, and sensitivity. However, the dynamics of individual stereocilia from the mammalian cochlea in response to a known bundle stimulus has not been quantified. We developed a novel high-speed system, which dynamically stimulates and tracks individual inner-hair-cell stereocilia from male and female rats. Stimulating 2-3 of the tallest stereocilia within a bundle (nonuniform stimulation) caused dissimilar stereociliary displacements. Stereocilia further from the stimulator moved less, but with little delay, implying that there is little slack in the system. Along the axis of mechanical sensitivity, stereocilium displacements peaked and reversed direction in response to a step stimulus. A viscoelastic model explained the observed displacement dynamics, which implies that coupling between the tallest stereocilia is effectively viscoelastic. Coupling elements between the tallest inner-hair-cell stereocilia were 2-3 times stronger than elements anchoring stereocilia to the cell's surface but were 10-10,000 times weaker than those of a well-studied non-cochlear hair bundle. Coupling was too weak to ensure that stereocilia move similarly in response to nonuniform stimulation at auditory frequencies. Our results imply that more uniform stimulation across the tallest stereocilia of an inner-hair-cell bundle in vivo is required to ensure stereociliary displacement similarity, increasing the speed, sensitivity, and magnitude of the receptor current.SIGNIFICANCE STATEMENT:Generation of the hair cell's receptor current is the first step in electrically encoding auditory information in the hearing organs of all vertebrates. The receptor current is shaped by mechanical coupling between stereocilia in each hair cell's hair bundle. Here we provide foundational information on the mechanical coupling between stereocilia of cochlear inner hair cells. In contrast to other types of hair cell, coupling between inner hair cell stereocilia is weak, causing slower, smaller, and less sensitive receptor currents in response to stimulation of few, rather than many, stereocilia. Our results imply that inner hair cells need many stereocilia to be stimulated in vivo to ensure fast, large, and sensitive receptor currents.

    View details for DOI 10.1523/JNEUROSCI.1588-22.2023

    View details for PubMedID 36746628

  • A chemo-mechanical cochleostomy preserves hearing for the in vivo functional imaging of cochlear cells. Nature protocols Kim, J., Ricci, A. J. 2023

    Abstract

    In vivo and real-time multicellular imaging enables the decoding of sensory circuits and the tracking of systemic drug uptake. However, in vivo imaging of the auditory periphery remains technically challenging owing to the deep location, mechanosensitivity and fluid-filled, bone-encased nature of the cochlear structure. Existing methods that expose the cochlea invariably cause irreversible damage to auditory function, severely limiting the experimental measurements possible in living animals. Here we present an in vivo surgical protocol that permits the imaging of cochlear cells in hearing mice. Our protocol describes a ventro-lateral approach for preserving external and middle ear structures while performing surgery, the correct mouse positioning for imaging cochlear cells with effective sound transmission into the ear, the chemo-mechanical cochleostomy for creating the imaging window in the otic capsule bone that prevents intracochlear fluid leakage by maintaining an intact endosteum, and the release of intracochlear pressure that separates the endosteum from the otic capsule bone while creating an imaging window. The procedure thus preserves hearing thresholds. Individual inner and outer hair cells, supporting cells and nerve fibers can be visualized in vivo while hearing function is preserved. This approach may enable future original investigations, such as the real-time tracking of ototoxic drug transport into the cochleae. The technique may be applied to the monitoring of sound-evoked functional activity in multiple cochlear cells, in combination with optogenetic tools, and may help to improve cochlear implantation in humans. The cochleostomy takes ~1 h and requires experience in surgery.

    View details for DOI 10.1038/s41596-022-00786-4

    View details for PubMedID 36599963

  • ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points. The Journal of cell biology Krey, J. F., Liu, C., Belyantseva, I. A., Bateschell, M., Dumont, R. A., Goldsmith, J., Chatterjee, P., Morrill, R. S., Fedorov, L. M., Foster, S., Kim, J., Nuttall, A. L., Jones, S. M., Choi, D., Friedman, T. B., Ricci, A. J., Zhao, B., Barr-Gillespie, P. G. 2022; 221 (4)

    Abstract

    The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell's cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed-TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience.

    View details for DOI 10.1083/jcb.202109134

    View details for PubMedID 35175278

  • Identifying targets to prevent aminoglycoside ototoxicity. Molecular and cellular neurosciences Kim, J., Hemachandran, S., Cheng, A. G., Ricci, A. J. 2022: 103722

    Abstract

    Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in our understanding of aminoglycoside ototoxicity, mechanisms of drug transport, and promising sites for intervention to prevent ototoxicity.

    View details for DOI 10.1016/j.mcn.2022.103722

    View details for PubMedID 35341941