Development and Regeneration

The Walters lab

Our lab in the Department of Otolaryngology - Head and Neck Surgery is interested in the study of development and regeneration, both in non-mammalian and mammalian models. In using this comparative approach, we aim to better understand the relative inability of various tissues to repair themselves after damage. In many vertebrate model systems, both the central and peripheral nervous systems demonstrate a remarkable capacity for self-renewal. However, these capabilities are either lost, or severely diminished in placental mammals.

This is particularly apparent with respect to the auditory system, where permanent sensorineural hearing loss is one of the most common long term disabilities in humans. This is due to the fact that cochlear hair cells in mammals are remarkably resistant to regeneration. Our current work focuses on the molecular determinants of late embryonic and early postnatal development of the inner ear sensory epithelia which not only allows us to ask fundamental biological questions about the inner ear and the senses of hearing and balance, but also informs regenerative strategies that may ultimately lead to enhanced rehabilitation in sensorineural hearing loss patients.

To test our hypotheses, we use a variety of experimental approaches that range from cell culture and gene targeting to fluorescent and electron microscopic approaches, and ultimately physiological and behavioral measures. The inner ear is a fascinating model system that is readily amenable to this bottom-up (or top-down) holistic type of approach and makes our work endlessly engaging and, we hope, constantly leading to promising and fascinating new research findings.

Current lab members

• Cindy Gregory-Moore, MD
• Anshuman Singh, PhD
• Sumana Ghosh, PhD
• Punam Thapa, MSc
• Graham Casey
• Kendra Stansak

Selected publications

• Walters, B.J., Coak, E., Dearman, J., Bailey, G., Yamashita, T., Kuo, B., Zuo, J. (2017), In vivo interplay of p27Kip1, GATA3, ATOH1, and POU4F3 converts nonsensory cells to hair cells in adult mice. Cell Reports, Apr 11, 19(2):307-320
• Walters, B.J., Diao, S., Zheng, F., Walters, B.J., Layman, W., Zuo, J. (2015), Pseudo-immortalization of postnatal cochlear progenitor cells yields a scalable cell line capable of transcriptionally regulating mature hair cell genes. Scientific Reports, 5: 17792.
• Walters, B.J., Yamashita, T., Zuo, J. (2015), Sox2-CreER mice provide a useful model for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies. Scientific Reports, 5:11621.
• Walters, B.J., Zuo, J. (2015), An inducible Sox10-rtTA mouse line for gene manipulation and fate mapping in the auditory and balance organs of the inner ear. J Assoc Res Otolaryngol.16(3):331-45. Cover Image
• Walters, B.J., Liu, Z., Crabtree, M., Coak, E., Cox, B.C., Zuo, J. (2014) Auditory hair cell-specific deletion of p27Kip1 in postnatal mice results in cell autonomous generation of new hair cells and preservation of hearing. J Neurosci.34(47): 15751-63. Featured Article

Patents

• Methods and Compositions of p27Kip1 Transcriptional Modulators. (2016) Zuo, J., Chen, T., Walters, B., Kuo, B., Walters, B.J., document #WO2014145205 A2.

Funding

• The National Institutes of Health - NIDCD (R01DC016365)
• NIH-NIDCD (R01DC016365-S1)
• The Office of Naval Research (N00014-18-1-2716)
• The American Otological Society