1991 |
Oesterle, Elizabeth C |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Hair Cell Regeneration @ University of Washington |
1 |
1994 — 1998 |
Oesterle, Elizabeth C |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Regulatory Signals in Hair Cell Regeneration @ University of Washington
Sensorineural hearing loss and vestibular disorders result primarily from the loss of sensory hair cells. The broad long-term goal of the proposed research is to develop methods for the treatment of sensorineural hearing loss and vestibular disorders based on understanding the molecular signals regulating hair-cell regeneration in avian and rodent models. Virtually nothing is known regarding the factors involved in the initiation and regulation of hair-cell genesis and differentiation in either the mature or developing inner ear. The experiments outlined in this proposal will test two specific hypotheses: (1) that growth factors are important in regulating the proliferation of hair-cell progenitors, and (2) that macrophages are important in initiating and regulating hair-cell regeneration, perhaps through their release of growth factors, cytokines, or proteases. The first hypothesis will be tested by (1) adding known growth factors to mature, cultured inner-ear epithelium and assessing the effects on cellular proliferation; (2) localizing growth factors and growth-factor receptors and their mRNA in normal and regenerating inner- ear epithelium; and (3) infusing growth factors into the in situ inner ear, and examining the effects on cellular proliferation. The hypothesis that macrophages are important in initiating and regulating the hair-cell regeneration response will be tested by determining whether media conditioned by activated monocytes can stimulate proliferation in cultured inner-ear sensory epithelia.
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1 |
1999 — 2003 |
Oesterle, Elizabeth C |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hair Cell Regeneration--Regulatory Signals @ University of Washington
It is estimated that 10 percent of the population is affected by sensorineural or "nerve" deafness that usually arises from sensory hair-cell loss or damage. Sensory deficits resulting from hair-cell loss have been considered irreversible because the production of human hair cells ceases before birth. In contrast, hair cells are produced postembryonically in the ears of cold-blooded and some warm-blooded vertebrates (birds); in some, thousands of new hair cells can be replaced through trauma-evoked regenerative proliferation. Recent evidence has shown that supporting cells proliferate and that new hair bundles can appear in vivo in the balance organs of mammals after antibiotic poisoning of hair cells. Also, supporting cells proliferate after the death of hair cells in organ cultures taken from the adult human ear. These findings suggest that hair-cell regeneration may be induced in the ears of humans. In order to develop clinical therapies that will bring about hair-cell regeneration in the human ear, we must identify the cellular and molecular signals responsible for triggering the regenerative proliferation of inner-ear supporting cells after hair-cell death, and determine how these cells go on to form hair cells. The goal of the proposed research is to identify factors that trigger regenerative replacement of hair cells in the ears of warm-blooded vertebrates during postembryonic life. This application proposes to investigate two hypotheses: (1) that growth factors are important in initiating and regulating the hair-cell regeneration response; and (2) that leukocytes are important in initiating hair-cell regeneration, perhaps through their release of growth factors. These hypotheses will be tested using a combination of techniques, including cell culture, immunocytochemistry, scanning and transmission electron microscopy, transfection, in situ hybridization, and the use of transgenic mice.
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2006 — 2009 |
Oesterle, Elizabeth C |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hair Cell Regeneration: Regulatory Signals @ University of Washington
[unreadable] DESCRIPTION (provided by applicant): It is estimated that 10% of the population is affected by sensorineural or "nerve" deafness that usually arises from sensory hair cell loss or damage. Sensory deficits resulting from hair cell loss have been considered irreversible because the production of human hair cells ceases before birth. In contrast, hair cells are produced postembryonically in the ears of cold-blooded and some warm-blooded vertebrates (birds); in some, thousands of new hair cells can be replaced through trauma-evoked regenerative proliferation. Evidence has shown that supporting cells proliferate and that new hair bundles can appear in vivo in the balance organs of mammals after antibiotic poisoning of hair cells. These findings suggest that hair cell regeneration may be induced in the ears of humans. In order to develop clinical therapies that will bring about hair cell regeneration in the human ear, we must identify the cellular and molecular signals responsible for triggering the regenerative proliferation of inner ear supporting cells after hair cell death, and determine how these cells go on to form hair cells. The goal of the proposed research is to identify factors that regulate regenerative replacement of hair cells in the ears of warm-blooded vertebrates during postembryonic life. This application proposes to investigate the following hypotheses: 1) Endogenous growth factors may negatively regulate inner-ear stem/progenitor cell proliferation, and 2) Robust regenerative proliferation of stem/progenitor cells in mature inner-ear SE may require a simultaneous release from negative regulation coupled with mitogenic signaling by the EGF and/or IGF pathways. These hypotheses will be tested using a combination of techniques, including expression profiling, cell localization, viral gene transfer, cell culture, and quantitative RT-PCR techniques. [unreadable] [unreadable] [unreadable]
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1 |
2011 — 2013 |
Oesterle, Elizabeth C |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hair Cell Regeneration: Regulatory Signals @ University of Washington
DESCRIPTION (provided by applicant): It is estimated that 10% of the population is affected by sensorineural or nerve deafness that usually arises from sensory hair cell loss or damage. Sensory deficits resulting from hair cell loss have been considered irreversible because the production of human hair cells ceases before birth. In contrast, hair cells are produced postembryonically in the ears of cold-blooded and some warm-blooded vertebrates (birds), and thousands of new hair cells can be replaced through trauma-evoked regenerative proliferation. Findings showing that supporting cells can proliferate in the balance organs of mature mammals and auditory organ of neonatal mammals under certain circumstances suggest that hair cell regeneration may be inducible in the human ear someday. In order to develop clinical therapies that will bring about hair cell regeneration in the human ear, we must identify the cellular and molecular signals responsible for triggering the regenerative proliferation of inner ear supporting cells after hair cell death, and determine how these cells go on to form hair cells. The goal of the proposed research is to identify factors that regulate regenerative replacement of hair cells in the ears of warm-blooded vertebrates during postembryonic life. This application proposes to investigate the following hypotheses: 1) Members of the TGF2 superfamily regulate progenitor cell proliferation in mature inner ear sensory receptor epithelia, and 2) Robust regenerative proliferation of progenitor cells in mature inner ear sensory epithelia may require a simultaneous release from tonic negative regulation coupled with mitogenic signaling by the TGF2 pathway. These hypotheses will be tested using a combination of techniques, including cell culture, quantitative RT-PCR, cell localization, and mouse genetics.
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1 |