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Teppei Noda Last modified date:2024.06.27

Assistant Professor / Otolaryngology
Department of Clinical Medicine
Faculty of Medical Sciences

Graduate School
Other Organization

 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Country of degree conferring institution (Overseas)
Field of Specialization
Otology, Developmental biology of inner ear, Auditory neuron regeneration
ORCID(Open Researcher and Contributor ID)
Total Priod of education and research career in the foreign country
Outline Activities
Working for clinical otolaryngology, education, and researching for inner ear development and regeneration.
Research Interests
  • Regeneration of primary auditory neutrons, Inner ear development, Hearing loss
    keyword : Regeneration of primary auditory neutrons, Inner ear development, Hearing loss
Academic Activities
1. Ruishuang Geng, Teppei Noda, Joanna F Mulvaney, Vincent Y W Lin, Albert S B Edge, Alain Dabdoub, Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea., PloS one, 10.1371/journal.pone.0148339, 11, 2, e0148339, 2016.02, BACKGROUND: In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points. RESULTS: We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity. CONCLUSION: A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study..
2. Koji Nishimura, Teppei Noda, Alain Dabdoub, Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea., PloS one, 10.1371/journal.pone.0170568, 12, 1, e0170568, 2017.01, Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion. Several transcription factors are known to regulate the development and differentiation of PANs. Here we systematically examined the spatiotemporal expression of five transcription factors: Sox2, Sox10, Gata3, Mafb, and Prox1 from early delamination at embryonic day (E) 10.5 to adult. We found that Sox2 and Sox10 were initially expressed in the proneurosensory cells in the otocyst (E10.5). By E12.75 both Sox2 and Sox10 were downregulated in the developing PANs; however, Sox2 expression transiently increased in the neurons around birth. Furthermore, both Sox2 and Sox10 continued to be expressed in spiral ganglion glial cells. We also show that Gata3 and Prox1 were first expressed in all developing neurons, followed by a decrease in expression of Gata3 and Mafb in type I PANs and Prox1 in type II PANs as they matured. Moreover, we describe two subtypes of type II neurons based on Peripherin expression. These results suggest that Sox2, Gata3 and Prox1 play a role during neurogenesis as well as maturation of the PANs..
3. Teppei Noda, Steven J Meas, Jumpei Nogami, Yutaka Amemiya, Ryutaro Uchi, Yasuyuki Ohkawa, Koji Nishimura, Alain Dabdoub, Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy., Frontiers in cell and developmental biology, 10.3389/fcell.2018.00016, 6, 16-16, 2018.02, Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs..
4. Teppei Noda, Shinya Oki, Keiko Kitajima, Tetsuro Harada, Shizuo Komune, Chikara Meno, Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo., Developmental biology, 10.1016/j.ydbio.2011.11.019, 362, 1, 83-93, 2012.02, The mouse inner ear develops from a simple epithelial pouch, the otocyst, with the dorsal and ventral portions giving rise to the vestibule and cochlea, respectively. The otocyst undergoes a morphological change to generate flattened saclike structures, known as outpocketings, in the dorsal and lateral regions. The semicircular canals of the vestibule form from the periphery of the outpocketings, with the central region (the fusion plate) undergoing de-epithelialization and disappearing. However, little is known of the mechanism that orchestrates formation of the semicircular canals. We now show that the area of canonical Wnt signaling changes dynamically in the dorsal otocyst during its morphogenesis. The genes for several Wnt ligands were found to be expressed in the dorsal otocyst according to specific patterns, whereas those for secreted inhibitors of Wnt ligands were expressed exclusively in the ventral otocyst. With the use of whole-embryo culture in combination with potent modulators of canonical Wnt signaling, we found that forced persistence of such signaling resulted in impaired formation both of the lateral outpocketing and of the fusion plates of the dorsal outpocketing. Canonical Wnt signaling was found to suppress Netrin1 expression and to preserve the integrity of the outpocketing epithelium. In addition, inhibition of canonical Wnt signaling reduced the size of the otocyst, likely through suppression of cell proliferation and promotion of apoptosis. Our stage-specific functional analysis suggests that strict regulation of canonical Wnt signaling in the dorsal otocyst orchestrates the process of semicircular canal formation..
5. Joanna F Mulvaney, Cathrine Thompkins, Teppei Noda, Koji Nishimura, Willy W Sun, Shuh-Yow Lin, Allison Coffin, Alain Dabdoub, Kremen1 regulates mechanosensory hair cell development in the mammalian cochlea and the zebrafish lateral line., Scientific reports, 10.1038/srep31668, 6, 31668-31668, 2016.08, Here we present spatio-temporal localization of Kremen1, a transmembrane receptor, in the mammalian cochlea, and investigate its role in the formation of sensory organs in mammal and fish model organisms. We show that Kremen1 is expressed in prosensory cells during cochlear development and in supporting cells of the adult mouse cochlea. Based on this expression pattern, we investigated whether Kremen1 functions to modulate cell fate decisions in the prosensory domain of the developing cochlea. We used gain and loss-of-function experiments to show that Kremen1 is sufficient to bias cells towards supporting cell fate, and is implicated in suppression of hair cell formation. In addition to our findings in the mouse cochlea, we examined the effects of over expression and loss of Kremen1 in the zebrafish lateral line. In agreement with our mouse data, we show that over expression of Kremen1 has a negative effect on the number of mechanosensory cells that form in the zebrafish neuromasts, and that fish lacking Kremen1 protein develop more hair cells per neuromast compared to wild type fish. Collectively, these data support an inhibitory role for Kremen1 in hair cell fate specification..
6. Teppei Noda, Noritaka Komune, Ryuji Yasumatsu, Nana Akagi Tsuchihashi, Akihiro Tamae, Nozomu Matsumoto, Kuniaki Sato, Ryutaro Uchi, Kensuke Koike, Takahiro Wakasaki, Risa Tanaka, Takashi Nakagawa, Therapeutic effect of Nivolumab for advanced / recurrent temporal bone squamous cell carcinoma., Auris, nasus, larynx, 10.1016/j.anl.2020.03.011, 47, 5, 864-869, 2020.10, OBJECTIVE: The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC. METHOD: Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined. RESULTS: We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2-54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%). CONCLUSION: We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC..
7. Teppei Noda, Steven J. Meas, Jumpei Nogami, Yutaka Amemiya, Ryutaro Uchi, Yasuyuki Ohkawa, Koji Nishimura, Alain Dabdoub, Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 10.3389/fcell.2018.00016, 6, online, 2018.02.
Membership in Academic Society
  • The Oto-Rhino-Laryngological Society of Japan