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URMC / Labs / Sakano Lab / Our Research

 

Our Research

FMRP and auditory brainstem development

We are interested in how FMRP (Fragile X protein) is involved in auditory brainstem development. The absence of FMRP causes Fragile X Syndrome which is the most common hereditary cause of autism spectrum disorder and these patients can experience hypersensitivity to sounds, or hyperacusis. The mouse model for this syndrome also exhibits auditory hypersensitivity as well as auditory seizures. Our previous studies have shown that FMRP is highly expressed in auditory brainstem nuclei compared to surrounding brainstem regions, across multiple species, suggesting an evolutionarily important role of FMRP in hearing. FMRP is also known as an mRNA binding protein, translational repressor and involvement in synaptic plasticity. Our lab is currently investigating the effects of FMRP absence on gene expression in the mouse cochlear nucleus and whether this leads to derangement of neuronal pathways that result in the auditory phenotype. We use molecular techniques such as RNA-seq, immunostaining, and Western blotting to answer these questions. The goal is to find potential treatments to restore these neuronal pathways that are likely involved in hyperacusis, and related disorders such as tinnitus and auditory neuropathies.

We are also investigating the relationship of nonsense mediated decay and FMRP in collaboration with the Maquat laboratory. Dr. Maquat and Dr. Kurosaki discovered that nonsense mediated decay (a type of mRNA regulation during development) is hyperactivated in iPSC cells derived from Fragile X syndrome patients. We are currently characterizing whether this is also the case in the mouse brain during development. The potential implication is that FMRP may have greater impact on gene expression and neuronal differentiation than currently appreciated.

Social disparity and ear disease

There is evidence that social disparities such as race and poverty have an impact on access to healthcare. Furthermore, studies have shown that the incidence of tympanostomy tube placement and medical followup in children with middle ear disease is higher among those from more affluent communities. In collaboration with Dr. Katherine Rieth who is investigating whether social disparities affect the healthcare outcomes of otolaryngology patients from the Upstate NY region, we are studying the impact of socioeconomic status on chronic ear disease management.