David Z. He graduated from Medical School of Southeast University with MD in 1983. He studied with Dr. Zhi-An Liang at the Shanghai Institute of Physiology, Chinese Academy of Sciences and received his PhD in Physiology in 1990. His postdoctoral training in the area of neuroscience was with Dr. Peter Dallos at Northwestern University. He was an Associate Professor at Creighton University School of Medicine between 2003 and 2007 and promoted to professor with tenure in 2007. Dr. He has published his studies on prestin, mechanotransduction, and hair cell development and repair in the prestigious journals such as Nature, Science, Nature Neuroscience, and PNAS. He was a regular member of NIH AUD Study Section between 2006 and 2010 and a regulate member of the CDRC/NIDCD study section between 2016 and 2020. He reviews manuscripts for Nature Neuroscience, Nature Review Neuroscience, Neuron, PNAS,and the Journal of Neuroscience. He has been invited to give seminars at Institutions in the US, Europe, Japan and China. He has received several awards, including the Sandy and David Marshall Award for Excellence in Auditory Science from American Hearing Research Foundation, Distinguished Research Career Award from Creighton University School of Medicine and University Research Award.
Teaching Interests
Neuroscience
Research Focus
Inner and outer hair cells (IHCs and OHCs) are the two types of mechanoreceptor cells in the mammalian cochlea of the inner ear that transduce mechanical stimuli into electrical activity. IHCs are the true sensory receptor cells that transmit auditory input to the brain. OHCs are a mammalian innovation with a unique capability to change length in response to changes in receptor potential. Using RNA-seq analysis of adult and aging mouse cochleae, we identified genes that are differentially expressed in these two cell types. The goal is to characterize genes underlying the unique structure and function of IHCs and OHCs as well as molecular mechanisms of biological aging of hair cells. We employ a variety of in vitro and in vivo experimental techniques including electrophysiology (system and cellular), immunocytochemistry, advanced imaging (electron and confocal microscopy), mouse genetics and molecular biology.
Not Applicable Beisel KW, He DZZ, Hallworth R & Fritzsch B (2008). Genetics of mechanoreceptor evolution and development. In: Audition, Vol. 1. (R. Hoy, P. Dallos, eds.), Elsevier, NY, pp 75-105 I 2008
Biomechanics at Micro- and Nanoscale Levels, Vol. III Currall B, Wang X, He DZZ. The effect of streptomycin and gentamicin on outer hair cell motility III, p. 5-12 2007
Articles
Hearing Research 2025
Frontiers in Cell and Developmental Biology 2025
Frontiers in Neurology 2024
Science Translational Medicine 2024
JCI: Insight Matthew A. Ingersoll, Richard D. Lutze, Chithra K. Pushpan, Regina G. Kelmann, Huizhan Liu, Mark T. May, William J. Hunter, David Z.Z. He, and Tal Teitz The widely used chemotherapy cisplatin causes permanent hearing loss in 40%–60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multidose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cell counts. Toxicity of the drug cotreatment was evaluated, and levels of phosphorylated ERK were measured. A dabrafenib dose of 3 mg/kg BW, twice daily, in mice, was determined to be the minimum effective dose, and it is equivalent to one-tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20–25 dB at the 3 frequencies tested, in both female and male mice, persisted for 4 months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), protected hearing in 2 mouse strains, and diminished cisplatin-induced weight loss. This study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss. 8(24), p. e171140 2023
iScience XiaofenLi, Qirui Zhao, Xiaojie Yu, Wenhan Cao, Yingyi Zhang, Wanying Feng, Liwen Jiang, David Z. He, RobertZ.Qi, and Pingbo Huang Cochlear and vestibular hair cells are highly specialized sensory receptors for hearing and balance. Here, we report a serendipitous identification of a hair-cell-specific organelle in neonatal mouse inner ear, which we name 'apicosome.' The apicosome is ∼500 nm in diameter and shows itinerant nature and transient appearance during development in cochlear hair cells. In contrast to cochlear hair cells, the apicosome persists in vestibular hair cells even in adult. The timing of apicosome translocation and disappearance in cochlear hair cells during development is correlated with kinocilium development and maintenance. The apicosome is not seen in supporting cells despite the fact that nascent supporting cells have microvilli and a primary cilium. Interestingly, transdifferentiated hair cells from supporting cells also contain apicosome, suggesting that it is unique to hair cells. Thus, our study identifies a previously undescribed organelle in hair cells and lays the foundation for further characterization of this specialized structure. 26, p. 106535 2023
Journal of Cell Science Huizhan Liu, Transcription co-factor LBH is necessary for the survival of cochlear hair cells
Huizhan Liu1,*, Kimberlee P. Giffen1,*, M’Hamed Grati2, Seth W. Morrill1, Yi Li1,3, Xuezhong Liu2, Karoline J. Briegel4,‡ and David Z. He1,‡ 2021
BMC Neuroscience Mian Zu, SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses
and auditory nerves
Mian Zu1,2,3,4†, Wei‑Wei Guo1,2,3,4†, Tao Cong1,2,3,4, Fei Ji1,2,3,4, Shi‑Li Zhang5, Yue Zhang1,2,3,4, Xin Song1,2,3,4,
Wei Sun6, David Z. Z. He7, Wei‑Guo Shi8* and Shi‑Ming Yang1,2,3,4* 2021
JCI: Insight Marisa Zallocchi , Zallocchi M, Hati S, Xu Z, Hausman W, Liu H, He DZ, Zuo J. Characterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss. JCI Insight. 2021 Mar 8;6(5):141561. doi: 10.1172/jci.insight.141561. 2021
JCI: Insight Marisa Zallocchi , Zallocchi M, Hati S, Xu Z, Hausman W, Liu H, He DZ, Zuo J. Characterization of quinoxaline derivatives for protection against iatrogenic-induced hearing loss. JCI: Insight, in press. 2021
Frontiers in Cellular Neuroscience Li Y, Endolymphatic Potential Measured From Developing and Adult Mouse Inner Ear 14, p. 584928 2020
Science Advances Ingersoll, Matthew A, BRAF inhibition protects against hearing loss in mice 49, p. eabd0561 2020
Cell and Tissue Research Paul T. Ranum, Alexander T. Goodwin, Hidekane Yoshimura, Diana L. Kolbe, William D. Walls, Jin-Young Koh, David Z.Z. He, Richard J.H. Smith. Interaction with ectopic cochlear crista sensory epithelium disrupts basal cochlear sensory epithelium development in Lmx1a mutant mice. 380, p. 435-448 2020
Frontiers in Neuroscience Giffen KP, Liu H, Kramer KL, He DZ. Expression of Protein-Coding Gene Orthologs in Zebrafish and Mouse Inner Ear Non-sensory Supporting Cells. Front Neurosci. 2019 Oct 18;13:1117. doi: 10.3389/fnins.2019.01117. eCollection 2019. PubMed PMID: 31680844; PubMed Central PMCID: PMC6813431 2019 Oct 18;13:1117, p. doi: 10.3389/fnins.2019.01117 2019
Scientific Reports Sonia M. Rocha-Sanchez, Olivia Fuson, Shikha Tarang, Linda Goodman, Umesh Pyakurel, Huizhan Liu, David Z. He, Marisa Zallocchi. Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage 8, p. 15119 2018
PLoS One Zhang Q, Liu HZ, Soukup GA, He DZ. Identifying miRNAs involved in aging of the stria vascularis. 9(11) 2014
Nature Communications Ren AJ, Wang K, Zhang H, Liu A, Ma X, Liang Q, Cao D, Wood JN, He DZ, Ding YQ, Yuan WJ, Xie Z, Zhang WJ. ZBTB20 regulates nociception and pain sensation by modulating TRP channel expression in nociceptive sensory neurons. 5, p. 4984 2014
Journal of Neuroscience Liu HZ, Pecka J, Zhang Q, Soukup GA, Beisel KW, He DZ. Characterization of transcriptomes of cochlear inner and outer hair cells. 34, p. 11080 2014
PLoS One Li Yi, Liu H, Li J, Zhang Q, Gong S, He DZ (2014) Morphology and ciliary motion of mucosa in the Eustachian tube of neonatal and adult gerbils 9(6), p. e99840 2014
Hearing Research 53. He* DZ, Lovas S, Ai Yu, Yi Li, Beisel KW (2013). Prestin at year 14: Progress and prospect. Hear Res pii: S0378-5955(13)00288-8. doi: 10.1016/j.heares.2013.12.002. 731, p. 3-11 2013
Brain Res Wang X, Yang SM, Jia SP, He* DZZ (2010). Prestin forms oligomer with four mechanically independent subunits. 1333, p. 28-35 2010
cytoskeleton He DZZ, Jia SP, Zuo J, Latham S, Riordan GP & Kachar B (2010). Prestin function and the structure of the lateral membrane of outer hair cells. 67, p. 43-55 2010
Not Applicable Jia SP, Yang SM, Guo WW & He* DZZ (2009). Fate of mammalian cochlear hair cells and stereocilia after loss of the stereocilia. 29 2009
Biochem. Biophys. Res. Commun. Kumano S, Tan X, He DZZ, Iida K, Murakoshi M & Wada H (2009). Mutation-induced reinforcement of prestin-expressing cells. 389, p. 569-574 2009
Developmental Dynamics Yang SM, Hou ZH, Young WY, Zhang JS, Yang G, Guo W, Sun JH, Hu YY, Yu N, Yu YP, He DZZ, Han DY & Yang X (2009). Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in mice. 238, p. 1897-1908 2009
Neuron Dallos P, Wu X, Cheatham MA, Gao J, Zheng J, Anderson CT, Jia S, Wang X, Cheng WH, Sengupta S, He DZ, Zuo J. Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification. 58, p. 333 2009
Developmental Neurobiology Yang SM, Guo WW, Hu YY, Sun YX, Hou ZH, Sun JH, Wang X, He DZ, Zhai SQ, Young WY, Han DY, Yang X. Smad5 haplo insufficiency leads to hair cell and hearing loss 69, p. 153 2009
Brain Res Wu XD, Wang X, Gao JG, Yu YL, Jia SP, Zheng J, Dallos P, He DZZ, Cheatham MA, Zuo J. Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification. 1210, p. 20 2008
Neuron Dallos P, Wu XD, Gao J, Wang X, Jia SP, Anderson CT, Zheng J, Cheatham MA, He* DZZ & Zuo* J. Prestin-based outer hair cell motility is necessary for Mammalian cochlear amplification. 58, p. 333 2008
Hearing Research Wang X, Jia SP, Currall B, Yang SM & He DZZ. Streptomycin and gentamicin have no immediate effect on outer hair cell electromotility. 234, p. 52 2007
Proceedings of the National Academy of Sciences Gao JG, Wang X, Wu XD, Aguinaga S, Huynh K, Jia SP, Matsuda K, Patel M, Zheng J, Cheatham MA, He* DZZ, Dallos* P & Zuo* J. Hyperpolarizing shifts of outer hair cell nonlinear capacitance and electromotility in prestin knockin mice do not change sensitivity or tuning. 104, p. 12542 2007
Journal of Physiology Albert JT, Winter H, Schaechinger TJ, Weber T, Wang X, He DZZ, Geisler H-S, Hendrich O, Zimmermann U, Gofert MC, Oliver D & Knipper M. Voltage-sensitive prestin orthologue expressed in zebrafish hair cells 580, p. 451-461 2007
Journal of Neuroscience Jia SP, Dallos P & He DZZ. Mechanoelectric transduction of adult inner hair cells 27, p. 1006-1014 2007
Not Applicable Jia SP, Zuo J, Dallos P & He DZZ. The cochlear amplifier: Is it hair bundle motion of outer hair cells? In: Auditory Mechanisms: Processes and Models. Nuttall A, Ren TY, Gillespie P, Grosh K, de Boer E (eds). Singapore, World Scientific Publ, p. 261-269 2006
Journal of Membrane Biology He DZZ, Zheng J, Kalinec F, Kakehata S, Santos-Sacchi J. Tuning in to the amazing outer hair cell: membrane wizardry with a twist and shout 209, p. 119-134 2006
Nature Neuroscience Jia SP, & He DZZ. Motility-associated hair-bundle motion in mammalian outer hair cells 8, p. 1028-1034 2005
Nature He DZZ, Jia SP, & Dallos P. Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea 429, p. 766-770 2004
Developmental Brain Research He DZZ, Cheatham MA, Pearce M, Vetter DE. Mouse outer hair cells lacking the alpha9 receptor are motile 148, p. 19-25 2004
Journal of Neuroscience He DZZ, Jia SP, & Dallos P. Prestin and the dynamtic stiffness of cochlear outer hair cells 23, p. 9089-9096 2003
Journal of Physiology He DZZ, Beisel KW, Chen L, Ding DL, Fritzsch B, & Salvi R. Chick hair cells do not exhibit voltage-dependent somatic motility 546, p. 511-520 2003
Hearing Research He DZZ, Jia SP, & Feng F. Thyroid hormone is not necessary for the development of outer hair cell electromotility 175, p. 183-189 2003
Not Applicable He DZZ. Mechanical responses of cochlear outer hair cells. Biophysics of the Cochlea. From Molecules to Models. Gummer, A.W. (ed.), World Scientific, p. 181-184 2003
Nature Liberman MC, Gao J, He DZZ, Wu XD, Jia SP,& Zuo J. Prestin is required for outer hair cell motility and the cochlear amplifier 419, p. 300-304 2002
Audiol. Neurootol. Zheng J, He DZZ, Long K, Madison LD, & Dallos P. Identification of differentially expressed cDNA clones from cochlear outer hair cells using PCR-based suppression subtractive hybridization 7, p. 277-288 2002
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Science Translational Medicine -0001
Elife -0001
Gao JG, Wang X, Wu XD, Aguinaga S, Huynh K, Jia SP, Matsuda K, Patel M, Zheng J, Cheatham MA, He DZZ, Dallos P & Zuo J (2006). Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier. Proc Natl Acad Sci USA (in press)
Wang X, Jia SP, Currall B, Yang SM & He DZZ (2007) Streptomycin and gentamicin have no immediate effect on outer hair cell electromotility. Hearing Res (under revision).
Beisel KW, He DZZ, Hallworth R & Fritzsch B (2007) Genetics of mechanoreceptor evolution and development. In: Audition, Vol. 1. (R. Hoy, P. Dallos, eds.), Elsevier, NY, (in press).
Currall B, Wang X, He DZZ (2007). The effect of streptomycin of streptomycin and gentamicin on outer hair cell motility. In: Biomechanics at Micro- and Nanoscale Levels, Vol. III, (H. Wada, ed). World Scientific Publ. (in press)
Publications
Cell Reports Huizhan Liu, Huizhan Liu, Kimberlee P. Giffen, Lei Chen, Heidi J. Henderson, Talia A. Cao, Grant A. Kozeny, Kirk W. Beisel, Yi Li, David Z. He,
Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells,
Cell Reports,
Volume 39, Issue 2,
2022,
110665,
ISSN 2211-1247,
https://doi.org/10.1016/j.celrep.2022.110665. 39 2022
Science Advances Kimberlee P. Giffen, Giffen KP, Li Y, Liu H, Zhao XC, Zhang CJ, Shen RJ, Wang T, Janesick A, Chen BB, Gong SS, Kachar B, Jin ZB, He DZ. Mutation of SLC7A14 causes auditory neuropathy and retinitis pigmentosa mediated by lysosomal dysfunction. Sci Adv. 2022 Apr 8;8(14):eabk0942. doi: 10.1126/sciadv.abk0942. Epub 2022 Apr 8. PMID: 35394837. 8 2022
28th Midwinter Meeting of the Association for Research in Otolaryngology Regeneration of Stereocilia of Cochlear Hair Cells by Math1 Gene Therapy Shi-Ming Yang, Wei Chen, Wei-Wei Guo, Jian-He Sun, Ying-Yan Hu, Shuping Jia, David He 33, p. 484 2010
28th Midwinter Meeting of the Association for Research in Otolaryngology The Size of R Group Rather Than the Charge Alone Plays a Role in Voltage Sensing of Prestin Xiaodong Tan, Jason Pecka, Kirk Beisel, David He 33, p. 577 2010
28th Midwinter Meeting of the Association for Research in Otolaryngology Smad4 Gene Plays Important Role on Inner Ear Development in Mice Shi-Ming Yang, Zhao-Hui Hou, Guan Yang, Ji-Shuai Zhang, Wei-Wei Guo, Jian-He Sun, Wie-Yen Young, David He, Xiao Yang 33, p. 32 2010