Research
Regeneration of Spiral Ganglion Neurons
Replacement of spiral ganglion neurons using pluripotent stem cell derived otic progenitors has allows partial recovery of hearing loss (Chen et al. Nature 2012). We have developed an immortalized multipotent otic progenitor (iMOP) cell that differentiates into cells that are morphologically similar to spiral ganglion neurons (Kwan et al. Stem Cell Reports 2015). iMOP cells cultured with denervated cochlear explants highlight the ability of iMOP cells to extend a thicker and thinner central neurites that innervates hair cells.
Epigenetic Regulation of Neuronal Differentiation
Changes in the chromatin during neuronal differentiation regulates transcription. We have shown that changes in the chromatin state affects iMOP proliferation and differentiation (Song et al. Stem Cell Reports 2017). We are interested in the nucleosome repositioning activities of Chd7 and Chd4 during neuronal differentiation. Using both iMOP cells and conditional knockout animals, we seek to understand the underlying molecular mechanism of the chromodomain helicase DNA bidning proteins during neuronal differentiation.
Prevention of Hair Cell Loss
During cellular replacement of spiral ganglion neurons, survival of hair cells and supporting cells may provide molecular cues to facilitate regeneration. Surviving hair cells provide targets for innervating peripheral neurites from iMOP-derived neurons. Supporting cells provide cues for survival of spiral ganglion neurons (Stankovic et al. 2004). We show that increased phosphorylation of Chk1, a DNA damage response protein, promotes survival of supporting cells and indirectly promotes hair cell survival (Jadali et al. Frontiers in Neuroscience 2017) .