Andrew Forge. The loss of the sensory hair cells from the cochlea (the hearing organ) is the major cause of deafness. Loss of the hair cells from vestibular system is a major contributor to balance dysfunction and the predominant underlying cause of falls in the elderly. The work in the laboratory aims at:
Understanding how hair cells die and the reasons for the progressive increase in hair cell loss once initiated, and identifying possible for pharmaceutical interventions to protect hair cells from lethal damage and/or prevent the progression of hair cell loss once initiated.
Characterising the process of repair of the cochlear and vestibular sensory epithelia when hair cells die; the cytoskeletal re-arrangements through which the non-sensory supporting cells that surround each hair cell close the lesions; and the subsequent molecular and cellular nature of the re-organisation of the sensory epithlelia that occurs following hair cell loss
Regeneration of hair cells and possible cell replacement strategies, including the use of progenitor cells derived from inner tissues and of stem cells
The maintenance of the inner ears environment that enables the proper functioning of hair cells and how that environment changes when hair cells die so that the likely ability of replacement hair cells to function properly can be assessed. A major part of this work involves investigations of intercellular communication via gap junctions, and the role of gap junctions and connexins in repair and recovery processes in the inner ear.
The work involves the use of whole animal models and organotypic cultures. Techniques have been developed for the maintenance of inner ear tissues of mammals, chickens and newts in culture. Hair cell regeneration occurs spontaneously in the inner ears of non-mammalian vertebrates; the examination of chicks and newts provides enables comparisons with the mammalian inner ear. We have also been able to maintain the vestibular sensory epithelia from humans in organotypic culture. The human tissue can be obtained from patients undergoing operations for acoustic neuromas and this presents the only opportunity to examine human inner ear tissues under experimental conditions. We are in the process of establishing a national consortium of surgeons who operate on such patients in order to obtain human vestibular material for our studies.
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