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Jian Zuo, PhD

Chair, Department of Biomedical Sciences

Professor

Jian Zuo

Contact

School of Medicine
Biomedical Sciences
Neuroscience (Master of Science)
Biomedical Sciences (Doctorate)
Biomedical Sciences (Master of Science)
CRISS II - Criss 2

Jian Zuo, PhD

Chair, Department of Biomedical Sciences

Professor

Jian Zuo obtained his B.S. in Biomedical Engineering in Huazhong University of Science and Technology in Wuhan, China in 1985. He then immigrated to US for his PhD in Physiology from UCSF in 1993. After postdoc training in Rockefeller University, he became a faculty at St. Jude Children’s Research Hospital in Memphis since 1998. After 20 years, he recently moved to Creighton University School of Medicine as the Chairman and Professor in the Dept. of Biomedical Sciences in April 2018. He has published >100 research articles and >20 reviews with high impacts. He currently has 2 R01 grants, 2 DoD grants and one MRC grant. He has trained many successful students and postdocs and has interests in commercialization of his discoveries.

Curriculum Vitae

Research Focus

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration (FDA)–approved drugs to prevent or treat it. We first performed high-throughput screens for small molecules that prevent cisplatin induced hearing loss in a cochlear derived cell line. The hit compounds were further validated in cochlear explants, zebrafish lateral-line neuromasts in vivo, and eventually in mouse and rat cochleae in vivo. We have so far identified and characterized several potent compounds that exhibit protection against not only cisplatin, but also antibiotics and noise induced hearing loss. We further investigated several targets of top compounds in knockout mouse models. To treat hearing loss, we first developed genetic mouse models in which hair cell regeneration occurred at adult ages. We utilized the state-of-the-art approaches such as conditional mouse genetics and 10X Genomics single-cell RNA seq analyses. Based on the mouse genetic results, we performed high-throughput screens of small molecules that mimic the genetics models. We further tested these top compounds in adult mice for hair cell regeneration. Combinatory applications of these top compounds could provide therapeutic intervention of hearing loss in clinics.

Department

Biomedical Sciences

Position

Professor

Articles

  • Frontiers in Cellular Neuroscience
    Zhenhang Xu, Xu Z, Tu S, Pass C, Zhang Y, Liu H, Diers J, Fu Y, He DZ and Zuo J (2022) Profiling mouse cochlear cellmaturation using 10 Genomics single-cell transcriptomics. Front. Cell. Neurosci. 16:962106.doi: 10.3389/fncel.2022.962106 2022
  • J Neurosci
    Lukashkina VA,, Lukashkina VA, Levic S, Simes P, Xu Z, DiGuiseppi JA, Zuo J*, Lukashin AN*, Russell IJ*. In vivo optogenetics reveals homeostatic control of cochlear sensitivity by supporting cells. Submitted. (* Co-corresponding authors), p. 5660–5671 2022
  • European Journal of Medicinal Chemistry
    Hati S,, Hati S, Zallocchi M, Hazlitt R, Li Y, Vijayakumar S, Min J, Rankovic Z, Lovas S, Zuo J. AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss. Eur J Med Chem. 2021 Dec 15;226:113849. doi: 10.1016/j.ejmech.2021.113849. Epub 2021 Sep 20. PMID: 34560429; PMCID: PMC8608744. 2021
  • Frontiers in Cellular Neuroscience
    Xu Z,, Xu Z, Rai V, Zuo J. TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae. Front Cell Neurosci. 2021 Nov 8;15:759223. doi: 10.3389/fncel.2021.759223. PMID: 34819838; PMCID: PMC8606527. 2021
  • Scientific Reports
    Urbanek ME, Urbanek ME, Zuo J. Genetic predisposition to tinnitus in the UK Biobank population. Sci Rep. 2021 Sep 13;11(1):18150. doi: 10.1038/s41598-021-97350-z. PMID: 34518561; PMCID: PMC8437971. 2021
  • Journal of Molecular Biology
    Iconaru LI,, Iconaru LI, Das S, Nourse A, Shelat AA, Zuo J, Kriwacki RW. Small Molecule Sequestration of the Intrinsically Disordered Protein, p27Kip1, Within Soluble Oligomers. J Mol Biol. 2021 Sep 3;433(18):167120. doi: 10.1016/j.jmb.2021.167120. Epub 2021 Jun 29. PMID: 34197833; PMCID: PMC8658733. 2021
  • Cell Reports
    Zhang XD, , Zhang XD, Thai PN, Ren L, Perez Flores MC, Ledford HA, Park S, Lee JH, Sihn CR, Chang CW, Chen WC, Timofeyev V, Zuo J, Chan JW, Yamoah EN, Chiamvimonvat N. Prestin amplifies cardiac motor functions. Cell Rep. 2021 May 4;35(5):109097. doi: 10.1016/j.celrep.2021.109097. PMID: 33951436; PMCID: PMC8720583. 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. PMID: 33476306. 2021
  • JCI: Insight
    Zallocchi M, , 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):e141561. doi: 10.1172/jci.insight.141561. PMID: 33476306; PMCID: PMC8021103. 2021
  • Science Advances
    Ingersoll MA,, Ingersoll MA, Malloy EA, Caster LE, Holland EM, Xu Z, Zallocchi M, Currier D, Liu H, He DZZ, Min J, Chen T, Zuo J, Teitz T. BRAF inhibition protects against hearing loss in mice. Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. PMID: 33268358; PMCID: PMC7821884. 2020
  • PLoS Genetics
    , Zhu GJ, Gong S, Ma DB, Tao T, He WQ, Zhang L, Wang F, Qian XY, Zhou H, Fan C, Wang P, Chen X, Zhao W, Sun J, Chen H, Wang Y, Gao X, Zuo J, Zhu MS, Gao X, Wan G. Aldh inhibitor restores auditory function in a mouse model of human deafness. PLoS Genet. 2020 Sep 24;16(9):e1009040. doi: 10.1371/journal.pgen.1009040. PMID: 32970669; PMCID: PMC7553308. 2020
  • Sci Rep
    Rai V, , Rai V, Wood MB, Feng H, Schabla NM, Tu S, Zuo J. The immune response after noise damage in the cochlea is characterized by a heterogeneous mix of adaptive and innate immune cells. Sci Rep. 2020 Sep 16;10(1):15167. doi: 10.1038/s41598-020-72181-6. PMID: 32938973; PMCID: PMC7495466. 2020
  • Zhu GJ, Ma DB, Tao T, Wei-Qi He WQ, Wang F, Qian XY, Zhou H, Fan C, Wang P, Chen X, Zhao W, Sun J, Chen HQ, Wang Y, Gao X, Zuo J, Wan G, Gao X, Zhu MS. Aberrant Espin expression mediates the auditory pathology in a mouse model of the human DFNA15 deafness. Submitted. 2019
  • Neuroscience Letters
    DiGuiseppi J, Zuo J. The awesome power of optogenetics in hearing research. Neuroscience Letters, 2019 May 14: 701:175-9. 
    701, p. 175-9 2019
  • Scientific Reports
    Takahashi S, , Takahashi S, Yamashita T, Homma K, Zhou Y, Zuo J, Zheng J, Cheatham MA. Deletion of exons 17 and 18 in prestin's STAS domain results in loss of function. Sci Rep. 2019 May 3;9(1):6874. doi: 10.1038/s41598-019-43343-y. PMID: 31053797; PMCID: PMC6499820. 2019
  • Journal of Medicinal Chemistry
    Hazlitt RA, , Hazlitt RA, Teitz T, Bonga JD, Fang J, Diao S, Iconaru L, Yang L, Goktug AN, Currier DG, Chen T, Rankovic Z, Min J, Zuo J. Development of Second-Generation CDK2 Inhibitors for the Prevention of Cisplatin-Induced Hearing Loss. J Med Chem. 2018 Sep 13;61(17):7700-7709. doi: 10.1021/acs.jmedchem.8b00669. Epub 2018 Aug 24. PMID: 30091915; PMCID: PMC6443376. 2018
  • PLoS Genetics
    Yamashita T, Zheng F, Finkelstein D, Kellard Z, Robert C, Rosencrance CD, Sugino K, Easton J, Gawad C, Zuo J. High-resolution transcriptional dissection of in vivo Atoh1-mediated cochlear hair cell conversion identifies Isl1 as a co-reprogramming factor. Published: July 31, 2018 PLOS Genetics https://doi.org/10.1371/journal.pgen.1007552 2018
  • PLoS Genetics
    Yamashita T,, Yamashita T, Zheng F, Finkelstein D, Kellard Z, Carter R, Rosencrance CD, Sugino K, Easton J, Gawad C, Zuo J. High-resolution transcriptional dissection of in vivo Atoh1-mediated hair cell conversion in mature cochleae identifies Isl1 as a co-reprogramming factor. PLoS Genet. 2018 Jul 31;14(7):e1007552. doi: 10.1371/journal.pgen.1007552. PMID: 30063705; PMCID: PMC6086484. 2018
  • J Exp Med
    Teitz T, Fang J, Goktug AN, Bonga JD, Diao S, Hazlitt RA, Iconaru L, Morfouace M, Currier D, Zhou Y, Umans RA, Taylor MR, Cheng C, Min J, Freeman B, Peng J, Roussel MR, Kriwacki R, Guy RK, Chen T, Zuo J. CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss. J. Experimental Medicine, 2018 April 2; 215(4): 1187-1203. doi: 10.1084/jem.20172246. Epub 2018 Mar 7. PMID: 29514916
    215(4), p. 1187-1203 2018
  • Frontiers in Cellular Neuroscience
    Steyger PS, Cunningham LL, Esquivel CR, Watts KL, Zuo J. Editorial: Cellular Mechanisms of Ototoxicity. Front Cell Neurosci. 2018 Mar 27;12:75. doi: 10.3389/fncel.2018.00075. eCollection 2018.
    12:75 2018
  • journal of Medicinal Chemistry
    Hazlitt RA, Min J, Zuo J. Progress in the development of preventative drugs for cisplatin-induced hearing loss, Invited Mini-perspective, J. Med Chem. J Med Chem. 2018 Feb 1. doi: 10.1021/acs.jmedchem.7b01653. [Epub ahead of print] PMID: 29361217 2018
  • Journal of American Chemical Society
    Ban D, , Ban D, Iconaru LI, Ramanathan A, Zuo J, Kriwacki RW. A Small Molecule Causes a Population Shift in the Conformational Landscape of an Intrinsically Disordered Protein. J Am Chem Soc. 2017 Oct 4;139(39):13692-13700. doi: 10.1021/jacs.7b01380. Epub 2017 Sep 21. PMID: 28885015; PMCID: PMC5962290. 2017
  • Salehi P,, Salehi P, Zallocchi M, Vijayakumar S, Urbanek M, Giffen KP, Li Y, Hati S, Zuo J. In silico transcriptomics identifies FDA-approved drugs and biological pathways for protection against cisplatin-induced hearing loss. Submitted. -0001
  • Tu S, , Tu S, Zuo J. Systematic single cell RNA sequencing analysis reveals unique transcriptional regulatory networks of Atoh1-mediated hair cell conversion in adult mouse cochleae. Submitted. -0001

Federal

  • R01DC015444-01 ZUO (PI) 09/01/2016-08/31/2020 (NCE)
    NIH/NIDCD
    Discovery of in vivo small molecules for hearing protection against cisplatin and noise
    Goals of Project: To optimize our top hit to generate a lead compound by improving local delivery methods and by performing sequential analyses including medicinal chemistry.

Awards

  • The Wennergren Foundation Award
    2011 The Wennergren Foundation Award, Stockholm, Sweden
  • The Hartwell Foundation Biomedical Research Collaboration Award
    2009-2012 The Hartwell Foundation 2009 Biomedical Research Collaboration Award, USA
  • The Hartwell Individual Biomedical Research Award
    2007-2010 The Hartwell Individual Biomedical Research Award, USA
  • The Richard J. Bellucci Award for Excellence in Research on Hearing and Vestibular Science and Disorders
    2004 The Richard J. Bellucci Award for Excellence in Research on Hearing and Vestibular Science and Disorders, Creighton University, Omaha, NE, USA
    The Richard J. Bellucci Foundation
  • March of Dimes Basil O’Connor Starter Scholar Research Award
    1999-2001 March of Dimes Basil O’Connor Starter Scholar Research Award, USA