The loss of neurosensory function, particularly the sensations of hearing and vision has devastating affects on communication, education, occupation, and quality of life. Since neurosensory cells of the inner ear and retina are not replaced after damage or degeneration, such losses are permanent. The purpose of the Nebraska Center for the Molecular Biology of Neurosensory Systems is to characterize the genetic mechanisms controlling the development and maintenance of neurosensory functions and the corresponding pathology associated with relevant gene mutations to identify potential avenues for intervention. We will focus our efforts on promising regenerative medicine strategies such as the reconstitution of damaged cells through the use of pluripotent stem cells or de-differentiation and regeneration of post-mitotic cells in the inner ear and retina. These studies utilize specialized animal models that allow control of gene expression at specific critical points in development, with detailed evaluation of the associated findings at the molecular and phenotypic levels. To facilitate these studies, 3 independent research institutions have joined to build an interactive Center with a multidisciplinary approach designed to address to these well-defined objectives. With a core of 3 senior researchers and an exemplary External Advisory Committee, we have successfully mentored 14 junior faculty members and created a collaborative group united by similar thematic and mechanistic approaches. Our research has been facilitated by 3 scientific cores: a Mouse Genome Engineering core for the development of mouse models, a Microarray core for comprehensive assessment of gene expression levels and determination of possible genetic networks, and a Molecular Phenotyping/Histology core to study the results of experimental alterations. These cores are an important addition to the research infrastructure of all 3 institutions. In the second phase of this COBRE project, we will continue to support 6 junior researchers: 2 are studying the mechanisms of specific syndromes of blindness and deaf/blindness, 1 is concentrating on the development and enrichment of retinal stem cell populations, and 3 are studying the molecular pathways of inner ear differentiation with the goal of facilitating sensory regeneration. As those projects obtain external funding and rotate off Center funding, new projects will be added. The addition of new investigators, along with continued support of research activities and the operation of core facilities, will ensure a growing "critical mass" of collaboration that will sustain the Center, and enable participants to obtain external funding which will ensure its long term viability

Public Health Relevance

The loss of sensory abilities such as hearing and vision causes devastating affects on communication, education, occupation, and quality of life. Once mature sensory cells of the eye or ear are lost, they are not replaced, so that these losses have been permanent. By studying the genetic controls of development of the sensory cells in the retina and inner ear, the scientists in this Center will determine optimal approaches for therapies utilizing precursor cells that can develop into replacement cells and restore function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103471-10
Application #
8537960
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Program Officer
Caldwell, Sheila
Project Start
2003-09-30
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
10
Fiscal Year
2013
Total Cost
$2,002,387
Indirect Cost
$267,750
Name
University of Nebraska Medical Center
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Ka, Minhan; Condorelli, Gianluigi; Woodgett, James R et al. (2014) mTOR regulates brain morphogenesis by mediating GSK3 signaling. Development 141:4076-86
Tarang, Shikha; Weston, Michael D (2014) Macros in microRNA target identification: a comparative analysis of in silico, in vitro, and in vivo approaches to microRNA target identification. RNA Biol 11:324-33
Ogun, Oluwaseye Ayoola; B√ľki, Bela; Cohn, Edward S et al. (2014) Menopause and benign paroxysmal positional vertigo. Menopause 21:886-9
Basma, Hesham; Gunji, Yoko; Iwasawa, Shunichiro et al. (2014) Reprogramming of COPD lung fibroblasts through formation of induced pluripotent stem cells. Am J Physiol Lung Cell Mol Physiol 306:L552-65
Ogun, Oluwaseye Ayoola; Janky, Kristen L; Cohn, Edward S et al. (2014) Gender-based comorbidity in benign paroxysmal positional vertigo. PLoS One 9:e105546
Waters, Brian M; McInturf, Samuel A; Amundsen, Keenan (2014) Transcriptomic and physiological characterization of the fefe mutant of melon (Cucumis melo) reveals new aspects of iron-copper crosstalk. New Phytol 203:1128-45
Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich et al. (2014) MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Dev Biol 395:4-18
Browne, Caroline A; Hanke, Joachim; Rose, Claudia et al. (2014) Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction. Stress 17:471-83
Kelley, Philip M; Connor, Alicia L; Tempero, Richard M (2013) Lymphatic vessel memory stimulated by recurrent inflammation. Am J Pathol 182:2418-28
Ozturk, Ferhat; Li, You; Zhu, Xiujuan et al. (2013) Systematic analysis of palatal transcriptome to identify cleft palate genes within TGF?3-knockout mice alleles: RNA-Seq analysis of TGF?3 Mice. BMC Genomics 14:113

Showing the most recent 10 out of 14 publications