Research


Residency Application InformationEar, Nose & Throat_defaultStudent CoursesAreas of Giving
  • Development and Regeneration

    Our lab 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

    • Kristina Manning, MSc
    • Lauree Thomas, BS
    • Rob Wineski, BS
    • Cindy Gregory-Moore, MD
    • Jonathan Jones, BS

    Selected Publications

    •  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
    • Liu, Z., Liu, Z., Walters, B.J., Owen, T., Kopan, R., Zuo, J. (2013), In vivo visualization of Notch1 proteolysis reveals the heterogeneity of Notch signaling activity in the developing mouse cochlea. PLoS One.8(5):e64903. doi: 10.1371/journal.pone.0064903
    • Walters, B.J., Zuo, J. (2013), Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration. Hear Res.297:68-83.
    • Duncan, K.A., Walters, B.J., Saldanha, C.J. (2013), Traumatized and inflamed - but resilient: glial aromatization and the avian brain. Horm Behav. 63(2): 208-15.
    • Walters, B.J., Alexiades, N.G., Saldanha, C.J. (2011), “Intracerebral estrogen provision increases cytogenesis and neurogenesis in the injured zebra finch brain.” Dev Neurobiology. 71(2):170-81.
    • Saldanha, C.J., Walters, B.J., Fraley, G.S. (2010). “Neurons that co-localize aromatase and a kisspeptin-like immunoreactivity may regulate the HPG axis in the mallard drake (Anas platyrhyncos).”  Gen Comp Endocrinology.166(3):606-13.
    • Saldanha, C.J., Duncan, K., Walters, B.J. (2009). “Neuroprotective actions of brain aromatase.” Front  Neuroendocrinol.  30(2): 106-118.
    • Walters, B.J., Saldanha, C.J. (2008). “Glial aromatization increases the expression of bone morphogenetic protein-2 in the injured zebra finch brain.” J Neurochem.106(1): 216-23.
    • Wynne, R.D., Walters, B.J., Bailey, D.J., Saldanha, C.J. (2008). “Inhibition of injury-induced glial aromatase reveals a wave of secondary degeneration in the songbird brain.” Glia.56: 97-105.

     

    Patents

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