18. GOALS FOR FELLOWSHIP TRAINING AND CAREER Having Deaf family members, I have first hand experience of the difficulties that face those affected with communicative disorders. These experiences, and my love of science, have shaped my career path to auditory neuroscience. My overall career goal is to contribute to the amelioration of hearing loss through the application of basic science. It is through this goal that I propose to explore the utility of a novel agent, the stem cell, as a therapy for hearing loss. During the course of this exploration, I will receive training from the best auditory scientists and stem cell biologists in their fields. I will hone my skills in electrophysiology, molecular biology, cell biology, and neurochemistry. More importantly, I will develop many new skills and techniques ranging from novel animal surgeries to the molecular aspects of cell signaling. By the end of this project, I anticipate being a strong contributor in both auditory science and stem cell biology, and hope to advance a new mode of treatment for hearing loss. SPONSOR 19. NAME AND DEGREE(S) Douglas_h._D.. 20, POSITION/RANK Associate Professor 21. RESEARCH tNTERESTS/AREAS Cell and molecular biology of cochlear hair cell regeneration/effects of acoustic trauma and aminoglycoside treatment on hair cells/structure_ development & regeneration of the tectoral membrane/trauma-induced apoptosis in hair cells/stem cell biology RESEARCH PROPOSAL 22. DESCRIPTION (Do not exceed space provided) Hearing impairment has a profound effect on the American population, with almost thirty million people exhibiting some level of deafness or hearing loss. This disability impairs more people in terms of both numbers and economic impact than epilepsy, multiple sclerosis, spinal injury, stroke, Huntington's and Parkinson's diseases combined. The goal of this proposal is to investigate the therapeutic potential of stem cells transplanted in the auditory system. To this end, the first aim is to study the cellular signaling between stem cells and cochlear explants in vitro. The upregulation of growth factors and cell migration will be measured from stem cells in co-culture with organ of Corti explants.
The second aim i s to exploit the developmental potential of stem cells by defining the in vitro conditions in which neural stem cells may transdifferentiate into cochlear cell types. To address this aim, we will attempt to prolong organ of Corti explant viability to optimize conditions for neural stem cell transdifferentiation.
The final aim i s to utilize the regenerative capacities of stem cells by transplanting them into deafened animal models. To accomplish this, neural stem cells will be transplanted into the internal auditory meatus of a denervated animal model. Lastly, stem cells will be transplanted into the otic capsule of a deafened animal model. The hypothesis is that the transplanted stem cells will respond to environmental cues and differentiate into cochlear cells. The hope is that transplanted stem cells will prove to be therapeutically beneficial to hearing loss. PHS 416-1 (Rev. 12/98) Form Page 2 BB cc Individual NRSA Application t NAME (Lest, first, middle initial) Table of Contents ========================================Section End===========================================
| Parker, Mark A; Corliss, Deborah A; Gray, Brianna et al. (2007) Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hear Res 232:29-43 |
| Parker, Mark A; Anderson, Julia K; Corliss, Deborah A et al. (2005) Expression profile of an operationally-defined neural stem cell clone. Exp Neurol 194:320-32 |
| Parker, Mark A; Cotanche, Douglas A (2004) The potential use of stem cells for cochlear repair. Audiol Neurootol 9:72-80 |
