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Guocai Zhong PhD

TitleAssistant Professor
InstitutionUMass Chan Medical School
DepartmentGenetic and Cellular Medicine
AddressUMass Chan Medical School
366 Plantation Street, NERB
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentGene Therapy Center

    InstitutionT.H. Chan School of Medicine
    DepartmentGenetic and Cellular Medicine

    InstitutionT.H. Chan School of Medicine
    DepartmentRNA Therapeutics Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentImmunology and Microbiology Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMillennium MD/PhD Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science


    Collapse Biography 
    Collapse education and training
    Harbin Medical University, Harbin, , ChinaPHDPathobiology

    Collapse Overview 
    Collapse overview

    Guocai completed his PhD in pathobiology with training at the National Institute of Biological Sciences (NIBS), an HHMI-style research institute in China, where he co-discovered NTCP as an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV) — a breakthrough recognized by the 2021 Baruch S. Blumberg Prize and the 2022 Future Science Prize in Life Sciences. He then moved to the Scripps Research Institute as a postdoc (2013-2019) and developed a series of novel RNA switches, including a self-cleavage-based RNA switch capable of regulating gene expression of AAV-delivered therapeutics with a wide regulatory range in mice. In late 2019, Guocai established his independent laboratory at Shenzhen Bay Laboratory and Peking University Shenzhen Graduate School in Shenzhen, China. In the summer of 2022, he moved his lab to the RNA Therapeutics Institute and Horae Gene Therapy Center (now Department of Genetic & Cellular Medicine) at the UMass Chan Medical School. Zhong Lab's research has been centered on RNA switch engineering and the development of regulatable gene therapies.

    RNA switches, structured small noncoding RNA domains that control gene expression independent of any protein factors, are a class of very useful tools for exogenous, precise control of gene expression. They not only can be used in genetics studies for spatial & temporal manipulation of endogenous genes, but also can be used in vectored gene therapies for temporal or dosing control of therapeutic transgene expression, or in cell-based therapies for precise programming of engineered-cell functions. RNA switch thus represents a very promising platform technology that has the potential to enable future gene and cell therapy application to diverse diseases that can't be safely or effectively treated with the current gene or cell therapy technologies (learn more here). 

    Our group creates useful RNA switches and develops RNA switch-regulated gene therapies for diverse disease applications. A body of our prior studies have moved artificial RNA switches from working efficiently in vitro to now functioning with wide dynamic ranges in animals. These studies also established a strong proof of concept that RNA switches could enable safer and more effective applications and expand the use of in vivo gene therapies to broader disease indications.

    We are now very interested in the following three directions:

    1. Tool development: engineering parts (novel RNA switches, other RNA-based tools, therapeutic payloads) for the development of programmable gene therapies.

    2. Mechanistic studies: investigating how the in-house developed RNA switches work in mammalian cells.

    3. Gene therapy applications: developing programmable gene and cell-based therapies for fatal genetic diseases (e.g. Duchenne muscular dystrophy, generalized lipodystrophy), metabolic disorders (e.g. NASH, diabetes, obesity), infectious diseases (e.g. HIV infection,COVID-19), and cancers.

    Collapse Rotation Projects

    Rotation projects are available in the three areas of our lab's current research interests.


    Collapse Post Docs

    Chengzhi Du, PhD. Chengzhi received his PhD degree in Cancer Biology in 2019 from Institute of Biophysics, Chinese Academy of Sciences, Beijing. Since then, he joined Zhong Lab as a Postdoctoral Associate, initially at Peking University Shenzhen Graduate School, then moved with the lab to UMass Chan Medical School (5/20/2023-).



    Mengjia Lu, PhD. Mengjia was a graduate student in Zhong Lab. She joined the lab in late 2019 and received her PhD degree in Chemical Genomics in July 2023 from Peking University, China. As the lab then moved to UMass Chan Medical School, she rejoined the lab at UMass Med as a Postdoctoral Associate (10/16/2023-).



    Postdoctoral Positions Available

    We are seeking highly motivated postdoctoral researchers with a strong background in cellular and molecular biology, molecular physiology, RNA biology/biochemistry, or related fields in biological and biomedical sciences. Prior research experience in metabolic disease molecular physiology/therapy or cancer immunotherapies is highly desirable.

    To apply, please submit a cover letter and CV listing three references by email to Guocai Zhong at Guocai.Zhong@umassmed.edu.



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Tang X, Wang H, Yin Y, Zhong G. A peptide conjugate enables systemic injection of the morpholino inducer and more durable induction of T3H38 ribozyme-controlled AAV transgene in mice. Gene Ther. 2025 Mar; 32(2):163-171. PMID: 39939797.
      Citations:    
    2. Yao W, Li Y, Ma D, Hou X, Wang H, Tang X, Cheng D, Zhang H, Du C, Pan H, Li C, Lin H, Sun M, Ding Q, Wang Y, Gao J, Zhong G. Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs. Microbiol Spectr. 2023 Dec 12; 11(6):e0267623. PMID: 37943512.
      Citations:    
    3. Lu M, Yao W, Li Y, Ma D, Zhang Z, Wang H, Tang X, Wang Y, Li C, Cheng D, Lin H, Yin Y, Zhao J, Zhong G. Broadly Effective ACE2 Decoy Proteins Protect Mice from Lethal SARS-CoV-2 Infection. Microbiol Spectr. 2023 08 17; 11(4):e0110023. PMID: 37395664.
      Citations:    
    4. Ren W, Zhang Y, Rao J, Wang Z, Lan J, Liu K, Zhang X, Hu X, Yang C, Zhong G, Zhang R, Wang X, Shan C, Ding Q. Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant. mBio. 2023 04 25; 14(2):e0041623. PMID: 37010428.
      Citations:    
    5. Ren W, Ju X, Gong M, Lan J, Yu Y, Long Q, Kenney DJ, O'Connell AK, Zhang Y, Zhong J, Zhong G, Douam F, Wang X, Huang A, Zhang R, Ding Q. Characterization of SARS-CoV-2 Variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618 by Cell Entry and Immune Evasion. mBio. 2022 04 26; 13(2):e0009922. PMID: 35266815.
      Citations:    
    6. Ren W, Lan J, Ju X, Gong M, Long Q, Zhu Z, Yu Y, Wu J, Zhong J, Zhang R, Fan S, Zhong G, Huang A, Wang X, Ding Q. Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption. PLoS Pathog. 2021 11; 17(11):e1010053. PMID: 34748603.
      Citations:    
    7. Ou T, He W, Quinlan BD, Guo Y, Tran MH, Karunadharma P, Park H, Davis-Gardner ME, Yin Y, Zhang X, Wang H, Zhong G, Farzan M. Reprogramming of the heavy-chain CDR3 regions of a human antibody repertoire. Mol Ther. 2022 01 05; 30(1):184-197. PMID: 34740791.
      Citations:    
    8. Zhang Z, Zeng E, Zhang L, Wang W, Jin Y, Sun J, Huang S, Yin W, Dai J, Zhuang Z, Chen Z, Sun J, Zhu A, Li F, Cao W, Li X, Shi Y, Gan M, Zhang S, Wei P, Huang J, Zhong N, Zhong G, Zhao J, Wang Y, Shao W, Zhao J. Potent prophylactic and therapeutic efficacy of recombinant human ACE2-Fc against SARS-CoV-2 infection in vivo. Cell Discov. 2021 Aug 12; 7(1):65. PMID: 34385423.
      Citations:    
    9. Guo Y, He W, Mou H, Zhang L, Chang J, Peng S, Ojha A, Tavora R, Parcells MS, Luo G, Li W, Zhong G, Choe H, Farzan M, Quinlan BD. An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines. mBio. 2021 05 11; 12(3). PMID: 33975938.
      Citations:    
    10. Tran MH, Park H, Nobles CL, Karunadharma P, Pan L, Zhong G, Wang H, He W, Ou T, Crynen G, Sheptack K, Stiskin I, Mou H, Farzan M. A more efficient CRISPR-Cas12a variant derived from Lachnospiraceae bacterium MA2020. Mol Ther Nucleic Acids. 2021 Jun 04; 24:40-53. PMID: 33738137.
      Citations:    
    11. Quinlan BD, He W, Mou H, Zhang L, Guo Y, Chang J, Peng S, Ojha A, Tavora R, Parcells MS, Luo G, Li W, Zhong G, Choe H, Farzan M. An engineered receptor-binding domain improves the immunogenicity of multivalent SARS-CoV-2 vaccines. bioRxiv. 2020 Nov 18. PMID: 33236008.
      Citations:    
    12. Li Y, Wang H, Tang X, Fang S, Ma D, Du C, Wang Y, Pan H, Yao W, Zhang R, Zou X, Zheng J, Xu L, Farzan M, Zhong G. SARS-CoV-2 and Three Related Coronaviruses Utilize Multiple ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig. J Virol. 2020 10 27; 94(22). PMID: 32847856.
      Citations:    
    13. Zhong G, Wang H, He W, Li Y, Mou H, Tickner ZJ, Tran MH, Ou T, Yin Y, Diao H, Farzan M. A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo. Nat Biotechnol. 2020 02; 38(2):169-175. PMID: 31873216.
      Citations:    
    14. Mou H, Zhong G, Gardner MR, Wang H, Wang YW, Cheng D, Farzan M. Conditional Regulation of Gene Expression by Ligand-Induced Occlusion of a MicroRNA Target Sequence. Mol Ther. 2018 05 02; 26(5):1277-1286. PMID: 29567311.
      Citations:    
    15. Zhong G, Wang H, Li Y, Tran MH, Farzan M. Cpf1 proteins excise CRISPR RNAs from mRNA transcripts in mammalian cells. Nat Chem Biol. 2017 Aug; 13(8):839-841. PMID: 28628097.
      Citations:    
    16. Zhong G, Wang H, Bailey CC, Gao G, Farzan M. Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells. Elife. 2016 11 02; 5. PMID: 27805569.
      Citations:    
    17. Sun Y, Qi Y, Liu C, Gao W, Chen P, Fu L, Peng B, Wang H, Jing Z, Zhong G, Li W. Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus. J Virol. 2014 Jan; 88(1):237-48. PMID: 24155382.
      Citations:    
    18. Zhong G, Yan H, Wang H, He W, Jing Z, Qi Y, Fu L, Gao Z, Huang Y, Xu G, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes. J Virol. 2013 Jun; 87(12):7176-84. PMID: 23596296.
      Citations:    
    19. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13; 3. PMID: 25409679.
      Citations:    
    20. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13; 1:e00049. PMID: 23150796.
      Citations:    
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