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David Zhi-Zhou He, MD, PhD

Professor

Biomedical Sciences

D He

Contact

School of Medicine
Biomedical Sciences
Graduate School
Neuroscience (Master of Science)
Biomedical Sciences (Doctorate)
Biomedical Sciences (Master of Science)
Translational Hearing
CRISS I - Criss 1 - 315

David Zhi-Zhou He, MD, PhD

Professor

Biomedical Sciences

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.

Department

Biomedical Sciences

Position

Professor

Books

  • 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

  • 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
  • -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

Presentations

  • ARO Meeting 2023
  • Poster presentation at Annual meeting of association for research in otolarynogology at San Joe 2020
  • Four Poster presentations at Annual Meeting of Association for Research in Otolaryngology in San Joe 2020
  • Poster presentation at Annual Meeting of Association for Research in Otolaryngology at San Joe 2020
  • Podium presentation at 5th International meeting on hearing loss, Beijing, China 2019
  • Presentation on 5th International meeing on hearing loss, Beijing, China 2019
  • Seminar given at Biology Department of University of Iowa 2015
  • Poster presentation at 48th ARO meeting in Baltimore 2015
  • Podium presentation at 48th ARO meeting in Baltimore 2015
  • Poster presentation at Inner Ear Biology Meeting in Japan 2014
  • Podium presentation at Inner Ear Biology Meeting in Japan 2014
  • Poster Presentation at annual ARO meeting 2014
  • Poster presentation at annual Meeting 2014
  • Seminar speaker at Boys Town National Research Hospital 2010
  • Seminar Speaker at Qinghua University 2010
  • Poster Presentation, ARO meeting 2010
  • Oral Presentation ARO Meeting 2010
  • Poster Presentation at ARO meeting 2010
  • Seminar Speaker at Tohoko University 2010
  • Invited Seminar Speaker, Medical University of South Carolina 2010
  • 46th Inner Ear Biology Meeting 2009
  • Seminar speaker at Johns Hopkins University 2009
  • departmental seminar 2009
  • ARO poster 2009
  • ARO annual meeting 2009
  • ARO poster presentation 2009
  • Seminar speaker at University of Michigan 2008
  • invited seminar at boys town national research hospital 2008
  • 5th International Conference on Nanotechnology in Biomedical Research 2008
  • invited seminar at NIDCD, NIH 2008
  • Poster, Annual meeting of the Association for research of otolaryngology 2008
  • Poster, Annual Meeting of the Association for research of otolaryngology 2008
  • Podium presentation at Annual meeting of the Association for Research in Otolaryngology 2008
  • Department Seminar 2008
  • Keynote speaker, 30th international conference on comparative physiology, Brazil 2007
  • Invited Seminar Speaker at UC Irvine 2007
  • Feature Presentation at 4th International Conference on Hearing Sciences, Beijing, China 2007
  • Invited Seminar at NIDCD/NIH, Bethesda 2007
  • Poster Presentation at ARO Annual Meeting, Denver 2007
  • Podium Presentation at ARO Annual Meeting, Denver 2007
  • Seminar speaker at University of North Dakota 2006
  • Seminar speaker at University of Washington 2006
  • Prsentation at ARO, Baltimore 2006
  • ARO Annual Meeting at Baltimore 2006
  • Seminar speaker at Depts of Otolaryngology, and Physiology and Biophysics, University of Colorado 2005
  • 2nd Swiss-Japan conference on biomechanics, Kyoto, Japan 2005
  • Invited lecture at Koyto University, Japan 2005
  • Auditory Mechanisms: Processes and Models. Oregon, Portland, USA 2005
  • Invited seminar speaker at NIDCD (NIH) 2005
  • XXXI International conference of Physiology 2005
  • Poster presentation at aro annual meeting 2005
  • Assoc. Res. Otolaryngology mid winter meeting. 2005
  • Gordon research conference on neurobiology of the sensory system in Hong Kong 2004
  • Gordon Research Conference in Hong Kong 2004
  • ARO Annual Meeting in Florida. 2004
  • ARO Meeting in Florida 2004
  • ARO Meeting in florida 2004
  • The 2nd International Symposium on Future Medical Engineering Based on Bio-Nanotechnology, Japan. 2003
  • ARO Meeting 2003
  • ARO Meeting 2003
  • ARO Meeting 2003
  • ARO Meeting 2003
  • ARO Meeting 2003
  • Presentations at the Annual Meeting of the Association for Research on Otolaryngology in Florida 2003
  • ARO mid-winter meeting in Florida 2003
  • Seminar speaker at UNMC 2002
  • Presentation at the Meeting of Biophysics of the Cochlea in Germany 2002

Awards

  • Intramural Research Award
    Receiving Award from Health Future Foundation of CUSOM

Consulting

  • ZRG1 IFCN-E Study Section
    Panel Member
    The panel of which Dr. He was a member reviewed grants for NIH.
    NIH
    2021 - 2021
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