Head & Neck Surgery

Mirna Mustapha Research Lab


Our long-term goal is to understand the pre- and post-synaptic mechanisms
of auditory neuropathy using human and mouse genetics. 


Research Focus

1. Thyroid hormone (TH) dependent development of neural circuitry in the cochlea. 

postnatal development

The sense of hearing originates in the cochlea, a structure in the inner ear, where information about timing, frequency, and intensity of sounds is transmitted from the hair cells via highly efficient ribbon synapses to the spiral ganglion neurons. Cochlear neurogenesis starts in the embryonic period in mice and matures during the first two postnatal weeks. Postnatal development of the cochlea is an essential stage in synaptogenesis since the innervation pattern at birth very different from the normal distribution seen at the onset of hearing on postnatal day 12-14. 


During this early period, excess synapses and spiral ganglia are pruned and the cochlea develops a more mature neural architecture. Any defect at this stage of maturation can result in dysfunctional hearing due to pre- or post-synaptic auditory neuropathy.


Credit: Nikolas Blevins, MD


However, the molecular mechanisms underlying this critical developmental stage are poorly understood. Cochlear maturation also coincides with a critical period for TH production.  Deficiencies in TH production or function will likely affect the expression of functionally important proteins that are involved in the structural development and physiological processes of the inner ear. 

Our ongoing research investigates the role of TH-regulated genes on the timely coordination of a complex set of neural differentiation events in the maturing cochlea.  This includes further examining the mechanisms that prompt progression of synapse formation and functional maturation.  We are using mouse genetic manipulations and a variety of molecular and physiological approaches to identify new genes involved in regulating cochlear hair cell innervation.

spiral-ganglionsynapse-formation spiral-ganglion

2. The development and function of the hair cell through the action of motor molecules with scaffolding proteins.

Our second line of research focuses on functional characterization of myosin motors in establishing and maintaining afferent fiber connection with hair cells, which is essential to hearing.  The discovery of new molecular motors that are involved in sensory perception and knowledge of their specific roles and cargos will lead to better understanding of the differentiation and function of inner ear hair cells.

Our studies utilize mouse models and are designed to improve our understanding of the molecular processes that regulate innervation of the organ of Corti. We anticipate that mouse and human genetic studies will be synergistic in advancing our understanding of hearing loss. In the long term, we would like to translate our data from mice into understanding human deafness.  Our ultimate goal is to contribute to the development of therapeutic approaches and strategies to connect regenerated hair cells to the central nervous system.

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