Our Research
Defining the Mechanisms of damage and repair following Acoustic Trauma
Exposure to loud sounds can permanently damage the hair cells of the inner ear and their synaptic connections to auditory nerves. This damage is a major contributor to hearing loss and can lead to debilitating conditions such as tinnitus (ringing in the ears) and hyperacusis (increased sound sensitivity). The mechanisms underlying noise-induced damage—including excessive glutamate signaling and excitotoxicity—are remarkably similar between mammalian cochleae and the lateral line organs of zebrafish, making zebrafish an excellent model for studying these processes.
Our lab has developed both mechanical and pharmacological methods to mimic noise-induced damage in zebrafish lateral line organs. Using advanced techniques such as live imaging of calcium signaling in sensory nerves and tracking macrophage responses to injury, we are addressing three key questions: How do sensory nerves respond to damaging stimuli, and do their intrinsic properties change following injury? What role does the inflammatory response play in both damage and repair? How do synaptic connections regenerate and sensory organs recover after injury?
By understanding the mechanisms of damage and repair in the zebrafish lateral line system, we aim to identify potential therapeutic targets for treating sensorineural hearing loss in humans.
Identifying Strategies to Prevent and Reverse Cisplatin-Induced Hair Cell Damage
Cisplatin is a highly effective cancer treatment, but it frequently causes permanent hearing loss that can emerge years after treatment ends. Evidence suggests that cisplatin makes the inner ear more vulnerable to noise damage, though how this happens remains unclear. Understanding this increased vulnerability is critical for protecting hearing in cancer survivors without compromising cisplatin’s ability to fight cancer.
Hair cells in the inner ear are particularly susceptible to cisplatin damage. Our zebrafish studies show that even low doses of cisplatin disrupt mitochondrial homeostasis in hair cells that otherwise appear normal and functional. We believe this mitochondrial damage is what makes hair cells vulnerable to additional threats like moderate noise exposure. We are currently investigating how mitochondrial disruption creates this vulnerability in zebrafish and, in collaboration with with Mark Rutherford’s research team, testing potential treatments to promote inner ear repair in cisplatin-treated mice.
Behavioral Consequences of Lateral-Line Organ Damage
The zebrafish lateral line is a well-established model for investigating the cellular mechanisms of hair-cell organ damage, yet few studies evaluate the functional consequences through behavioral analysis. We have developed a sensitive and quantitative assay of lateral line-mediated behavior. Lateral line organs are mechanosensory structures that detect water flow and contribute to positive rheotaxis—the ability to orient and swim against oncoming currents. Using a custom microflume to generate calibrated flow stimuli, we record zebrafish behavioral responses under infrared light to eliminate visual cues, then quantify body position and kinematics using DeepLabCut, a markerless pose estimation platform that employs deep neural networks for automated tracking. This approach enables us to quantify rheotactic performance and assess functional deficits in lateral line-mediated behavior following damage and throughout the recovery period.
Identifying novel regulators of afferent nerve regeneration and hair-cell reinnervation
Unlike the mammalian inner ear, where damage is permanent, zebrafish possess a remarkable ability to regenerate lost hair cells and sensory neurons in both their inner ears and lateral line organs. This regenerative capacity makes zebrafish an invaluable model for understanding the molecular mechanisms that could potentially restore hearing in humans.
Currently we are identifying the key molecular pathways that enable regeneration of lateral line nerves, with the goal of developing therapies to promote auditory nerve regeneration and hair cell reinnervation in the mammalian cochlea. By uncovering the mechanisms zebrafish use to regenerate sensory neurons, we may identify regenerative pathways that could be activated in mammals to restore lost auditory nerves.