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Matthew W. Kelley, Ph.D.

photo of Matthew Kelly

Chief
Section on Developmental Neuroscience

Chief
Laboratory of Cochlear Development

NIDCD/NIH
Porter Neuroscience Research Center
35 Convent Drive 1D-993
Bethesda, Maryland 20892
Phone: (301) 435-8075
Fax: (301) 480-3001
E-mail: kelleymt@nidcd.nih.gov

Mutations in a gene called Vangl2 lead to defects in the orientation of hair cell stereociliary bundles.
Mutations in a gene called Vangl2 lead to defects in the orientation of hair cell stereociliary bundles.
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Gene expression in the organ of Corti.
Gene expression in the organ of Corti.
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Dr. Kelley received his B.A. from Cornell University and his Ph.D. from the University of Virginia. Following a post-doctoral fellowship at the University of Washington, he became an Assistant Professor in the Department of Cell Biology at Georgetown University in 1996. In 2000 he moved to the NIDCD, first as Acting Chief and then (since 2004) as Chief of the Developmental Neuroscience Section. Dr. Kelley's laboratory works on the cellular and molecular development of the mammalian cochlea.

A targeted mutation in the Fgf8 gene results in a disruption in the development of pillar cells (red). Surface view of the basal turn of the mouse organ of Corti at embryonic day 16.  Filamentous actin in hair cells and supporting cells is labeled in green.  The myosin II heavy chain protein MYH14 (red) is strongly expressed in non-sensory cells in the medial half of the epithelium.
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A targeted mutation in the Fgf8 gene results in a disruption in the development of pillar cells (red). A targeted mutation in the Fgf8 gene results in a disruption in the development of pillar cells (red).
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A mutation in the Hedgehog signaling pathway results in extra hair cells in the cochlea. A mutation in the Hedgehog signaling pathway results in extra hair cells in the cochlea.
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Research Statement

The overall goals of the Developmental Neuroscience Section are to identify the molecular and cellular factors that play a role in the development of the sensory epithelium of the mammalian cochlea (the organ of Corti). The organ of Corti is comprised of at least 6 distinct cell types that are arranged in highly conserved mosaic. The generation of a specific number of each cell type and the arrangement of these cell types into a regular pattern are essential for the normal perception of sound; however, our understanding of the factors that play a role in the development of this structure is extremely limited.

Current research in the laboratory is focused on the mechanisms that control the number of cells that will develop with each distinct phenotype. Previous results have demonstrated that the number of cells that will develop as sensory hair cells is regulated through inhibitory interactions between neighboring cells. These results suggest that the possible cell fates within the cochlea may be arranged in a hierarchy and that as the number of cells that become specified to develop as a single phenotype increases, these cells then begin to produce inhibitory signals that force the remaining cells to develop with alternate fates.

A second area of interest is the mechanisms that control overall cellular pattern within the cochlea. The cellular pattern of the mammalian cochlea is arranged in a gradient such that one type of sensory cell is located on one edge of the epithelium and a second type of sensory cell is located on the opposite edge. At both edges the sensory cells are arranged in distinct rows. The factors that specify the formation of this pattern are unknown; however, preliminary results suggest that the Wnt signaling pathway may play a role in the development of this pattern.

Finally, recent work in the laboratory has begun to examine the molecular factors that regulate the development of planar polarity within the cochlea. All hair cells have a "V"-shaped stereociliary bundle located on their apical surface. In the cochlea, all stereociliary bundles are oriented such that the vertex of each "V" points in the same direction. The correct orientation of these bundles is required for normal hearing. Research in our laboratory has recently begun to identify the molecular signaling pathways that are required for the orientation of these bundles and future work will examine the specific roles of these pathways in the cochlea.

Lab Personnel

  • Elizabeth Driver, Staff Scientist, 301-435-8074 (Send e-mail)
  • Weise Chang, Biologist, 301-435-8074 (Send e-mail)
  • Zoe Mann, Post-doctoral Visiting Fellow, 301-435-8074 (Send e-mail)
  • Thomas Coate, Post-doctoral Fellow, 301-435-8074 (Send e-mail)
  • Alyssa Huebner, Postbaccalaureate IRTA Fellow, 301-435-8074 (Send e-mail)
  • Hanna Sherrill, Pre-doctorate IRTA, 301-435-8074 (Send e-mail)
  • Kevin Isgrig, Technical IRTA, 301-435-8074 (Send e-mail)
  • Michael Kelly, Post-doctoral Fellow, 301-435-8074 (Send e-mail)
  • Michael Hoa, Staff Clinician, 301-435-8074 (Send e-mail)
  • Joseph Burns, Post-doctoral Fellow, 301-435-8074 (Send e-mail)
Developmental Neuroscience Section Photo
Developmental Neuroscience Section

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