Mark E. Warchol, Ph.D.

Professor
Otolaryngology
Neuroscience
Speech and Hearing

Neurosciences Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-747-7186

  • 314-747-7230

  • 8115

  • Central Institute for the Deaf, Research/Administration Building, Rm. 2031, 4560 Clayton Avenue

  • mwarchol@wustl.edu

  • hearing, vestibular, sensory, development, regeneration, macrophage, microglia

  • Mechanisms of development, injury and repair in the vertebrate auditory system

Research Abstract:

Sensory transduction in the inner ear is mediated by mechanoreceptive hair cells. Unfortunately, hair cells can be injured or lost after exposure to noise, ototoxic drugs, or as part of normal aging. Such injury typically results in permanent hearing loss and/or disequilibrium. Our research focuses on the biological mechanisms that regulate the production of hair cells and the survival and growth of their afferent neurons. Present studies include:

Role of Inflammatory Cells in Sensory Development and Regeneration
Throughout the body, cells of the innate immune system are critically involved in the early stages of tissue repair. The cochleae of birds and mammals contain resident populations of macrophages and increased numbers of macrophages are observed after cochlear injury. We are examining whether recruited macrophages actively promote repair and/or regeneration in the avian inner ear. Additional studies are aimed at determining whether macrophages affect the survival and/or outgrowth of afferent neurons in the injured cochlea. Finally, we are using transgenic mice and zebrafish to characterize the activity and function of macrophages during the embryonic development of the inner ear.

FGF Signaling in Cochlear Regeneration
The avian cochlea has a remarkable ability to regenerate sensory hair cells after injury, and a major goal of our research is to understand the molecular basis of this regenerative process. An ongoing study, conducted in collaboration with the Lovett lab (Dept. of Genetics), is using Next-Gen sequencing to profile the transcriptome of the chick cochlea throughout the time course of regeneration. Additional data suggest that the lack of FGF signaling in the mature mammalian ear may be one factor that limits regenerative ability in mammals. We are presently collaborating with the Orntiz lab (Dept. of Developmental Biology) to determine whether reactivating FGF signaling in the injured mouse cochlea can evoke some degree of sensory repair.

Selected Publications:

Slattery EL and Warchol ME. (2010) Cisplatin Ototoxicity Blocks Sensory Regeneration in the Avian Inner Ear. Journal of Neuroscience 30: 3473-3481.

Warchol ME and Montcouquiol M. (2010) Maintained Expression of the Planar Cell Polarity Molecule Vangl2 and Reformation of Hair Cell Orientation in the Regenerating Inner Ear. Journal of the Association for Research in Otolaryngology 11: 395-406.

Bird JE, Daudet N, Warchol ME, Gale JE. Rapid Elimination of Dying Sensory Hair Cells Maintains Epithelial Integrity in the Avian Inner Ear. (2010) Journal of Neuroscience 30: 4535-4543

D.M. Alvarado, R.D. Hawkins, S. Bashiardes, R.A. Veile, K.E. Powder, M.K. Sprigs, J.D. Speck, M.E. Warchol, M. Lovett (2011) An RNAi-Based Screen of transcription Factor Genes Indentifies Pathways Necessary for Sensory Regeneration in the Avian Inner Ear. Journal of Neuroscience 31: 4535-4543

S.-H. Hu, J.M. Jones, M.E. Warchol and D.M. Ornitz (2012) Differentiation of the Lateral Compartment of the Cochlea Requires a Temporally Restricted FGF20 Signal. PLoS Biology 10: e1001231

Last Updated: 8/17/2012 11:14:11 AM

GFP-expressing macrophages in the developing mouse cochlea
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