Sensory Regeneration Lab
Principal Investigator:
Mark Warchol, PhD, Professor, Otolaryngology-Head & Neck Surgery
Overview
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.
Research Projects
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.
Ototoxic Injury and Regeneration in Zebrafish
Cisplatin is one of the most widely-used and effective chemotherapeutic agents. Ototoxicity is a common side-effect of cisplatin therapy, leading to permanent hearing loss in ~30% of treated individuals. We have recently found that cisplatin targets both inner ear sensory cells (hair cells) and their associated supporting cells. Ongoing experiments are using zebrafish to identify the cellular effects of cisplatin on the supporting cells of the lateral line and the inner ear.
Lab Team
- Mark Warchol, PhD
- Angie Schrader
- Vikrant Borse
Current Funding
R01 DC006283 Mechanisms of Sensory Regeneration 9/04-3/15
National Institute on Deafness and Communicative Disorders
(National Institutes of Health)
R21 DC010909 Effects of Cisplatin on Inner Ear Stem Cells 7/11 – 6/13
National Institute on Deafness and Communicative Disorders
(National Institutes of Health)
Publications
Warchol ME, Schwendener RA and Hirose K (2012) Depletion of Resident Macrophages Does Not Alter Sensory Regeneration in the Avian Cochlea. PLoS One 7: e51574
Hu S-H, Jones JM, Warchol ME and D.M. Ornitz DM (2012) Differentiation of the Lateral Compartment of the Cochlea Requires a Temporally Restricted FGF20 Signal. PLoS Biology 10: e1001231
Audo I and Warchol ME (2012) Retinal and Cochlear Toxicity of Drugs: New Insights into Mechanisms and Detection. Current Opinion in Neurology 25: 76-85
Alvarado DM, Hawkins RD, Bashiardes S, Veile RA, Powder KE, Sprigs MK, Speck JD, Warchol ME, Lovett M (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
Warchol ME (2011) Sensory Regeneration in the Vertebrate Inner Ear: Differences in Molecules and Species. Hearing Research 273: 72-79
Sajan SA, Rubenstein JL, Warchol ME, Lovett M. (2011) Identification of Direct Downstream Targets of Dlx4/5 During Early Inner Ear Development. Human Molecular Genetics 20: 1262-1273.
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.
Slattery EL and Warchol ME (2010) Cisplatin Ototoxicity Blocks Sensory Regeneration in the Avian Inner Ear. Journal of Neuroscience 30: 3473-3481.
Bird JE, Daudet N, Warchol ME, Gale JE (2010) Rapid Elimination of Dying Sensory Hair Cells Maintains Epithelial Integrity in the Avian Inner Ear. Journal of Neuroscience 30: 4535-4543
Kim E, Hyrc HL, Speck J, Lundberg YW, Salles FT, Kachar B, Goldberg MP, Warchol ME, and Ornitz DM (2010) Regulation of cellular calcium in vestibular supporting cells by Otopetrin-1. Journal of Neurophysiology 104: 3439-3450
Warchol ME (2010) Cellular Mechanisms of Aminoglycoside Ototoxicity. Current Opinion in Otolaryngology-Head and Neck Surgery 18: 454-458
Goodyear RJ, Christiansen JR, Zia B, Gale JE, Warchol ME, Corwin JT, and Richardson GP (2010) Identification of Hair-Cell Soma-1 (HCS-1) Antigen as Otoferlin. Journal of the Association for Research in Otolaryngology 11: 573-586
Contact Us
Mailing address
660 S. Euclid Ave.
Campus Box 8115
St.Louis, MO 63110
Physical address
4560 Clayton Ave.
Rm 2209D (office), 2110 (lab)
St. Louis, MO 63110