To detect sounds and have a sense of balance, we rely on our inner ear organs, the cochlea, and vestibular organs. Within them are sensory hair cells that are mechanosensitive yet susceptible to damage and irreversibly lost. The Cheng lab is interested in understanding the mechanisms underlying the development and regeneration of these sensory hair cells.
The Grillet lab focuses on understanding how sensory cells in the inner ear detect sounds, and in particular, which molecules provide force-sensitivity to the “antenna-like” structure that covers these cells. The lab uses genetics to perturb and study these molecules in the mouse, mimicking human genetics forms of hearing loss.
Our laboratory works on inner ear development and regeneration, as well as on the biology of sensory hair cells, the mechanosensitive cells of the inner ear. Using molecular biological and bioinformatics-based approaches, we aim to fundamentally understand the mechanisms of inner ear cell regeneration in animals such as chickens that recover naturally from hearing loss. We further utilize stem cell-based in vitro assays to assess suitable regenerative targets that can be activated with drugs, and exploring reprogramming as well as cell transplantation strategies for the treatment of hearing loss.
We study how things can go wrong in the auditory/vestibular system and potential ways of fixing it. Using unbiased approaches with zebrafish as our animal model, we have identified the key players for the function of sensory hair cells and auditory/vestibular neural circuits in the brain. Our goal is to understand hearing loss and vestibular dysfunction at the molecular level.
Hearing loss arises from breakdowns in sound processing by the auditory system. Our goal is to understand sound processing mechanistically so that new strategies for treating hearing impairment can be developed. We use physics, mathematics, and computing to build models of the ear’s components that explain and predict how the auditory system works.
(1) We investigate the mechanical and molecular underpinnings of hair cell mechanoelectrical transduction with a focus upon the role of the lipid bilayer and the hair bundle mechanics.
(2) We are developing nonototoxic antibiotics.
(3) We investigate synaptic specializations driving information transfer from the hair cell to the CNS.
We are working towards understanding the mechanisms and potential treatments for chronic middle ear infections, the largest cause of permanent hearing loss in the developing world. We are investigating why sensory hearing loss occurs in these infections and have developed novel therapeutics aimed at clearing infections and to regenerate the tympanic membrane.
Our research aims to overcome major unmet medical needs of the hearing-impaired people: 1) the need to see individual cells in the living inner ear to establish precise diagnosis, 2) the need for liquid biopsy of the inner ear to guide therapy, 3) the need for biological therapies for hearing loss, 4) the need for better devices for hearing restoration.