I currently have two independent projects funded by NIDCD/NIH and by the Hearing Health Foundation.

The first project studies the molecular machinery involved in the activity-dependent remodeling of the cytoskeleton in the inner ear sensory organelles, which are known as stereocilia. We recently found that the stability of these actin-filled projections depends on the constant influx of calcium through the mechano-electrical transduction (MET) channels that are located at the tips of stereocilia (Velez-Ortega, et al., eLife, 2017). We found that the blockage of MET channels or the breakage of their gating tip links leads to the shortening of stereocilia; but once the blockage is removed or the tip links regenerate, stereocilia are able to regrow. Based on the changes in stereocilia height in response to variations in the resting MET current, I hypothesize that the stereocilia actin cytoskeleton exhibits activity-dependent plasticity. This project constitues the first step in the search for the molecular players involved in this type of cytoskeleton remodeling.

The second project studies the role of TRPA1 channels in the inner ear. TRPA1 is an ion channel mostly known for its role as an "irritant sensor" in pain-sensing neurons. Functional TRPA1 channels are also expressed in the inner ear. However, given that genetically-modified mice lacking TRPA1 channels have normal hearing and balance, the role of these channels in the inner ear remains unknown. Noise exposure leads to the production of some of the cellular "irritants" that activate TRPA1 channels. Therefore, we hypothesized that TRPA1 channels could sense noise-induced damage in the cochlea. When we exposed adult mice to mild noise levels we observed a temporary increase in hearing thresholds that lasted several days. Mice lacking TRPA1 channels, however, recovered significantly faster than mice with normal TRPA1 expression. This project will explore whether, after noise exposure, TRPA1 activation contributes to the temporary shift in hearing thresholds to allow the cochlea enough time to repair or recover from the noise-induced tissue damage.

---