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My laboratory is interested in the molecular basis of inner ear development, including morphogenesis, cell fate specification, axon guidance and sensory cell differentiation. The vertebrate inner ear houses the sensory organs for hearing and balance. Sound reaches these sensory cells through a series of conductive elements that comprise the outer and middle ears. Components of the inner ear include a fluid-filled epithelial sac and resident neuronal ganglion cells, all surrounded by loose mesenchyme and bone. These tissues originate on the side of the head, either from the ectodermally-derived otic placode, the neural crest, the presomitic mesoderm or the endoderm. Because of these varied embryonic origins, ear malformations often occur in the context of developmental problems in other organs or tissues, leading to syndromic forms of deafness. Over 400 forms of syndromic deafness have been characterized in humans. In other cases, deafness is the only known defect, and in those cases the responsible genes are often associated with some specialized function of inner ear sensory cells. In addition to hearing loss, genetic defects in ear formation or function can also lead to balance disorders . At present, there are hundreds of genes expressed in the embryonic ear that need to be functionally analyzed for their role in ear development and function.
Our lab primarily uses chicken and mouse as animal models in our research. We have a specific interest in studying the Wnt signaling pathway and the roles of microRNAs , a small class of non-coding RNAs that serve to regulate gene expression. Ongoing collaborations with other research labs inform our choice of candidate genes to explore and manipulate. We use gene transfer techniques including infection with viral vectors or electroporation of plasmid DNA (in chicken embryos) to manipulate the levels of candidate molecules during development. Both overexpression and knockdown approaches can be informative in revealing the normal function of a candidate gene. Our hope is that the outcome of our research endeavors will lead to the design of new therapeutic treatments for deafness and balance disorders. For example, we have designed a study to use viral gene transfer to deliver microRNAs into the drug-damaged mouse cochlea to attempt to induce hair cell regeneration and rescue hearing loss.
We are collaborating with the Kuhn lab (Purdue) to study the neural tropism of Zika virus in the developing neural tube and inner ear. We are exploring whether Zika virus displays preferential infection of neural progenitors in specific regions of the brain or inner ear, with the goal of gaining a better understanding of how infection leads to developmental defects in the nervous system and hearing loss.
Our lab primarily uses chicken and mouse as animal models in our research. We have a specific interest in studying the Wnt signaling pathway and the roles of microRNAs , a small class of non-coding RNAs that serve to regulate gene expression. Ongoing collaborations with other research labs inform our choice of candidate genes to explore and manipulate. We use gene transfer techniques including infection with viral vectors or electroporation of plasmid DNA (in chicken embryos) to manipulate the levels of candidate molecules during development. Both overexpression and knockdown approaches can be informative in revealing the normal function of a candidate gene. Our hope is that the outcome of our research endeavors will lead to the design of new therapeutic treatments for deafness and balance disorders. For example, we have designed a study to use viral gene transfer to deliver microRNAs into the drug-damaged mouse cochlea to attempt to induce hair cell regeneration and rescue hearing loss.
We are collaborating with the Kuhn lab (Purdue) to study the neural tropism of Zika virus in the developing neural tube and inner ear. We are exploring whether Zika virus displays preferential infection of neural progenitors in specific regions of the brain or inner ear, with the goal of gaining a better understanding of how infection leads to developmental defects in the nervous system and hearing loss.
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Ankita Thawani,Nabilah H Sammudin, Hannah S Reygaerts, Alexis N Wozniak,Vidhya Munnamalai,Richard J Kuhn,Donna M Fekete
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2019)
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2019)
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2019)
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