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Deron Herr, Ph.D. "Exploring new modalities for the treatment of hearing loss thru the study of SIP signaling" Deron Herr - The purpose of the proposed research is to exploit a newly discovered genetic model for hearing loss 1) Characterize molecular mechanisms responsible for cochlear degeneration. 2) Use this information to investigate new drugs to prevent hearing loss. We recently reported the identification of a genetic knockout mouse that displays profound degenerative hearing loss and balance defects. These defects are due to a rapid but progressive pattern of inner ear degeneration that is distinct from other previously reported mutant mice. This pattern is consistent with a defect that is more relevant to certain types of degenerative hearing loss in humans. Further study of this mouse model is likely to identify previously unknown molecular mechanism of hearing loss, and more importantly, potential drug targets for preventing deafness.
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library of past projects funded
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   The above cells have been engineered to express S1P receptors to study the roles these receptors play in processes that are important to inner ear function. The presence of green fluorescence indicates the expression of the receptors. |
2009 Update The first part of this study, which was funded by a 2008 Capita Foundation Auditory Research grant generated cell lines that will allow us to identify drugs that stimulate the S1P receptors. In continuing this project, we are in the process of identifying specific cell-death molecules that are activated in the degenerative cochlea of our mutant mice, whereas, the next phase of this project will involve testing of drug candidates that are isolated in small molecule screens. The inner ear is a delicate organ that cannot be regenerated once it is damaged. Recently, we’ve made the surprising discovery that a growth factor known as sphingosine 1-phosphate (S1P) is required to prevent degeneration of the cochlea. This inner ear maintenance occurs through the activation of a specific receptor known as S1P2. Currently, we are pursuing two aspects of this process. 1) Through the continued use of knockout mice and engineered cell lines, we are characterizing the molecular processes involved in cochlear degeneration. 2) We are developing methods of stimulating the S1P2 pathway to prevent inner ear degeneration. The ultimate purpose of this project is to develop new drugs that can effectively prevent hearing loss that is caused by noise, chemotherapy, or the normal process of aging. |
 Inner ear hair cells were labeled with a fluorescent probe. Normally, these cells are organized in three orderly rows of outer hair cells and one row of inner hair cells as shown here. Cochlear degeneration is characterized by death of hair cells and loss of this stereotyped structure.  The organ of Corti. This is the sensory organ within the cochlea that transmits sound vibrations into nerve impulses. It is composed of a tectorial membrane, hair cells, supporting cells, and nerve fibers.  The round structure in the center of the image shows a cross section through the vestibulocochlear nerve carrying nerve fibers to the inner ear. The patch of cells on the left-hand side is the vestibular macula that senses balance. Click here to view article "Sphingosine 1-Phosphate (S1P) Signaling Is Required for Maintenance of Hair Cells Mainly via Activation of S1P2" published in the Journal of Neuroscience, February 7, 2007. |
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