Centers

Research Division for Fish Anti-stress and Disease Prevention and Control

Research Group on Fish Hypoxia Biology


 

 


 

PI: Wuhan Xiao, Ph.D., Professor 

Members: Xing Liu, Ph.D., Associate Professor; Jing Wang, Ph.D., Associate Professor; Xiaolian Cai, Ph.D., Associate Professor; Chunchun Zhu, Ph.D., Research Associate; Zhi, Li, Ph.D., Research Associate. 

Contact Us: 86-27-68780087 (office), 86-27-68780092 (lab)   

General Introduction:  

We mainly use economic fish and model fish (Zebrafish) as research materials. By gene editing, gene regulation, protein/protein interaction and gene function analysis (in vitro and in vivo), we aim to investigate fish in hypoxia tolerance and adaptation, innate immunity in response to viral infection and try to demonstrate the molecular mechanisms of the crosstalk between hypoxia signaling pathway and antiviral innate immunity signaling pathway. We seek to establish a foundation for molecular designing newfish strains with hypoxia tolerance and antiviral infection.

Research Interests: 

  • Molecular mechanisms of hypoxic tolerance in fish.
  • Molecular mechanisms of antiviral innate immunity.
  • Crosstalk between hypoxia signaling and antiviral innate immunity.

Representative Publications (* corresponding author)           

(1)   Zixuan Wang, Xiaoyun Chen, Chunchun Zhu, Sijia Fan, Jinhua Tang, Hongyan Deng, Xueyi Sun, Xing Liu*, Wuhan Xiao*. Direct lysine demethylation of IRF3 by the methytransferase SMYD3 attenuates antiviral innate immunity. PNAS, 2025, 122 (3): e2320644122.

(2)   Xing Liu, Chunchun Zhu, Shuke Jia, Hongyan Deng, Jinhua Tang, Xueyi Sun, Xiaoli Zeng, Xiaoyun Chen, Zixuan Wang, Wen Liu, Qian Liao, Huangyuan Zha, Xiaolian Cai, Wuhan Xiao*. Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity. PNAS, 2024, 121 (17): e2314201121.

(3)   Xing Liu, Jinhua Tang, Zixuan Wang, Chunchun Zhu, Hongyan Deng, Xueyi Sun, Guangqing Yu, Fangjing Rong, Xiaoyun Chen, Qian Liao, Shuke Jia, Wen Liu, Huangyuan Zha, Sijia Fan, Xiaolian Cai, Jian-Fang Gui, Wuhan Xiao*. Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3. Nature Communications, 2024, 15(1): 3533.

(4)   Xiaolian Cai, Rui Wang, Junji Zhu, Xiong Li, Xing Liu, Gang Ouyang, Jing Wang, Zhi Li, Chunchun Zhu, Hongyan Deng, Wuhan Xiao*. Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKKɛ. Cell Reports, 2024, 43(1): 113606.

(5)   Junji Zhu, Xiong Li, Xiaolian Cai, Ziwen Zhou, Qian Liao, Xing Liu, Jing Wang, Wuhan Xiao*. Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity. PNAS, 2023, 120(36): e2214956120

(6)   Xiaolian Cai, Ziwen Zhou, Junji Zhu, Xing Liu, Gang Ouyang, Jing Wang, Zhi Li, Xiong Li, Huanyuan Zha, Chunchun Zhu, Fangjing Rong, Jinghua Tang, Qian Liao, Wuhan Xiao*. Opposing effects of deubiquitinase OTUD3 in innate immunity against RNA and DNA viruses. Cell Reports, 2022, 39(10): 110920.

(7)   Junji Zhu, Xiong Li, Xiaolian Cai, Huangyuan Zha, Ziwen Zhou, Xueyi Sun, Fangjing Rong, Jinghua Tang, Chunchun Zhu, Xing Liu, Sijia Fan, Jing Wang, Qian Liao, Gang Ouyang, Wuhan Xiao*. Arginine monomethylation by PRMT7 controls MAVS-mediated antiviral innate immunity. Molecular Cell, 2021, 81(15); 3171-3186.

(8)   Xing Liu, Chunchun Zhu, Huanyuan Zha, Jinhua Tang, Fanjing Rong, Xiaoyun Chen, Sijia Fan, Chenxi Xu, Juan Du, Junji Zhu, Jing Wang, Gang Ouyang, Guangqing Yu, Xiaolian Cai, Zhu Chen, Wuhan Xiao*. SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation. EMBO Journal, 2020, 39 (11): e103285.

(9)   Yu Chen, Chi Zhou, Wei Ji, Zhichao Mei, Bo Hu, Wei Zhang, Dawei Zhang, Jing Wang, Xing Liu, Gang Ouyang, Jiangang Zhou, Wuhan Xiao*. ELL targets c-Myc for proteasomal degradation and suppresses tumor growth. Nature Communications, 2016, 7: 11057.

(10) Xi Feng, Xing Liu, Wei Zhang, Wuhan Xiao*. p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death. EMBO Journal, 2011, 30(16): 3397-3415.

       

   Other Publications(* corresponding author

2024

(1)     Rui Wang, Xiaolian Cai, Xiong Li, Jun Li, Xing Liu, Jing Wang, Wuhan Xiao*. USP38 promotes deubiquitination of K11-linked polyubiquitination of HIF1α at Lys796 to enhance hypoxia signaling. Journal of Biological Chemistry, 2024, 300 (1): 105532.

(2)     Zhi Li, Jun Li, Ziyi Li, Yanan Song, Yanyi Wang, Chunling Wang, Le Yuan, Wuhan Xiao*, Jing Wang*, Zebrafish mylipb attenuates antiviral innate immunity through two synergistic mechanisms targeting transcription factor irf3. PLoS Pathogens, 2024, 20(5): e1012227.

(3)     Mengjuan Chen, Yuqing Liu, Mingzhong Zuo, Chaohui Guo, Yongkun Du, Huifen Xu, Bianzhi Liu, Ming Liu, Wuhan Xiao*, Guangqing Yu*. NEDD8 enhances Hippo signaling by mediating YAP1 neddylation. Journal of Biological Chemistry, 2024, 300 (8): 107512.

(4)     Guangqing Yu, Le Yuan, Xiong Li, Mingzhong Zuo, Rui Wang, Mengjuan Chen, Yuqing Liu, Xing Liu, Wuhan Xiao*. Zebrafish phd1 enhances mavs-mediated antiviral responses in a hydroxylation-independent manner. Journal of Virology, 2024, 98 (9): e0103824.

(5)     Zixuan Wang, Chunchun Zhu, Xueyi Sun, Hongyan Deng, Wen Liu, Shuke Jia, Yao Bai, Wuhan Xiao*, Xing Liu*. Spring viremia of carp virus infection induces hypoxia response in zebrafish by stabilizing hif1α. Journal of Virology, 2024, e149124.

2023

(6) Hongyan Deng, Shuke Jia, Jinhua Tang, Fangjing Rong, Chenxi Xu, Xiaoyun Chen, Zixuan Wang, Chunchun Zhu, Xueyi Sun, Qian Liao, Wen Liu, Wenhua Li*, Wuhan Xiao*, Xing Liu*. SET7 methylates the deubiquitinase OTUB1 at Lys122 to impair its binding to E2 enzyme UBC13 and relieve its suppressive role on ferroptosis. Journal of Biological Chemistry, 2023, 299 (4): 103054.

(7)  Qian Liao, Hongyan Deng, Zixuan Wang, Guangqing Yu, Chunchun Zhu, Shuke Jia, Wen Liu, Yao Bai, Xueyi Sun, Xiaoyun Chen, Wuhan Xiao*, Xing Liu*, Deletion of prolyl hydroxylase 3 (phd3) in zebrafish facilitates hypoxia tolerance. Journal of Biological Chemistry, 2023, 299 (12): 105420.

(8)   Yanan Song, Sijia Fan, Dawei Zhang, Jun Li, Zhi Li, Ziyi Li, Wuhan Xiao*, Jing Wang*. Zebrafish maoc1 attenuates spring viremia of carp virus propagation by promoting autophagy-lysosome-dependent degradation of viral phosphoprotein. Journal of Virology, 2023, 97 (2): e0133822.

(9)   Qian Liao, Chunchun Zhu, Xueyi Sun, Zixuan Wang, Xiaoyun Chen, Hongyan Deng, Jinhua Tang, Shuke Jia, Wen Liu, Wuhan Xiao*, Xing Liu*. Disruption of sirtuin 7 in zebrafish facilities hypoxia tolerance. Journal of Biological Chemistry, 2023, 299 (8): 105074.

(10) Gang Ouyang, Qian Liao, Sijia Fan, Xiaolian Cai, Jing Wang, Xing Liu, Wuhan Xiao*. Zebrafish mavs is essential for antiviral innate immunity. Journal of Immunology, 2023, 210 (9): 1314-1323.

2022

(11) Xing Liu, Fangjing Rong, Jinhua Tang, Chunchun Zhu, Xiaoyun Chen, Shuke Jia, Zixuan Wang, Xueyi Sun, Hongyan Deng, Huangyuan Zha, Gang Ouyang, Wuhan Xiao*. Repression of p53 function by SIRT5-mediated desuccinylation at Lysine 120 in response to DNA damage. Cell Death and Differentiation, 2022, 29(4): 722-736.

(12) Jinhua Tang, Hongyan Deng, Zixuan Wang, Huanyuan Zha, Qian Liao, Chunchun Zhu, Xiaoyun Chen, Xueyi Sun, Shuke Jia, Gang Ouyang, Xing Liu*, Wuhan Xiao*. EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1αis repressed by SET7-catalyzed lysine methylation. Journal of Biological Chemistry, 2022, 298(6):101961.

(13) Xiaoyun Chen, Sijia Fan, Chunchun Zhu, Qian Liao, Jinhua Tang, Guangqing Yu, Xiaolian Cai, Gang Ouyang, Wuhan Xiao*, Xing Liu*. Zebrafish sirt5 negatively regulates antiviral innate immunity by attenuating phosphorylation and ubiquitination of mavs. Journal of Immunology, 2022, 209(6): 1165-1172.

(14) Xing Liu, Hongyan Deng, Jinhua Tang, Zixuan Wang, Chunchun Zhu, Xiaolian Cai, Fangjing Rong, Xiaoyun Chen, Xueyi Sun, Shuke Jia, Gang Ouyang, Wenhua Li*, Wuhan Xiao*. OTUB1 augments hypoxia signaling via its non-canonical ubiquitination inhibition of HIF-1αduring hypoxia adaptation. Cell Death and Disease. 2022, 13(6): 560.

(15) Zixuan Wang, Xiaoyun Chen, Sijia Fan, Chunchun Zhu, Hongyan Deng, Jinhua Tang, Xueyi Sun, Shuke Jia, Qian Liao, Wuhan Xiao*, Xing Liu*. Methyltransferase SMYD3 impairs hypoxia tolerance by augmenting hypoxia signaling independent of its enzymatic activity. Journal of Biological Chemistry, 2022, 292(12): 102633.

2021

(16) Junji Zhu, Xiong Li, Xueyi Sun, Ziwen Zhou, Xiaolian Cai, Xing Liu, Jing Wang, Wuhan Xiao*. Zebrafish prmt2 attenuates antiviral innate immunity by targeting traf6. Journal of Immunology, 2021, 207(10): 2570-2580.

(17) Ziwen Zhou, Xiaolian Cai, Junji Zhu, Zhi Li, Guangqing Yu, Xing Liu, Gang Ouyang, Wuhan Xiao*. Zebrafish otud6b negatively regulates antiviral responses by suppressing K63-linked ubiquitination of irf3 and irf7. Journal of Immunology, 2021, 207(1):244-256.

(18)  Qian Liao, Gang Ouyang, Junji Zhu, Xiaolian Cai, Guangqing Yu, Ziwen Zhou, Xing Liu, Wang Jing, Wuhan Xiao*. Zebrafish sirt7 negatively regulates antiviral responses by attenuating phosphorylation of irf3 and irf7 independently of its enzymatic activity. Journal of Immunology, 2021, 207(12): 3050-3059.

(19) Junji Zhu, Wuhan Xiao*. A proteomics protocol to identify stimulation-induced binding partners dependent on a specific gene in mammalian cells. STAR Protocols, 2021, 2(4): 100962.

2020

(20) Sijia Fan Jing WangGuangqing Yu Fangjing RongDawei ZhangChenxi Xu Juan DuZhi Li Gang Ouyang Wuhan Xiao*  . TET is targeted for proteasomal degradation by the PHD-pVHL pathway to reduce DNA hydroxymethylation. Journal of Biological Chemistry, 2020, 295(48): 16299-16313.

(21) Xiaolian Cai, Ziwen Zhou, Junji Zhu, Qian Liao, Dawei Zhang, Xing Liu, Jing Wang, Gang Ouyang, Wuhan Xiao*. Zebrafish hif-3a modulates erythropoiesis via regulation of gata-1 to facilitate hypoxia tolerance. Development, 2020, 147 (22): dev.185116.

(22) Guangqing Yu, Xing Liu, Dawei Zhang, Jing Wang, Gang Ouyang, Zhu Chen, Wuhan Xiao*. Zebrafish nedd8 facilitates ovarian development and the maintenance of female secondary sexual characteristics via suppression of androgen receptor activity. Development, 2020, 147(18): dev.194886.

(23) Zhi Li, Sijia Fan, Jing Wang, Xiaoyun Chen, Qian Liao, Xing Liu, Gang Ouyang, Hong Cao, Wuhan Xiao*. Zebrafish F-box protein fbxo3 negatively regulates antiviral response through promoting K27-linked polyubiquitination of the transcription factors irf3 and irf7. Journal of Immunology, 2020, 205(7):1897-1908.

(24) Guangqing Yu, Xiong Li, Ziwen Zhou, Jinhua Tang, Jing Wang, Xing Liu, Sijia Fan, Gang Ouyang, Wuhan Xiao*. Zebrafish phd3 negatively regulates antiviral responses via suppression of Irf7 transactivity independent of its prolyl hydroxylase activity.Journal of Immunology, 2020, 205(4):1135-1146.

(25) Gang Ouyang, Qian Liao, Dawei Zhang, Fangjing Rong, Xiaolian Cai, Sijia Fan, Junji Zhu, Jing Wang, Xing Liu, Xueqin Liu, Wuhan Xiao* . Zebrafish NF-kB/p65 is required for antiviral responses. Journal of Immunology, 2020, 204(11): 3019-3029.

(26) Junji Zhu, Xing Liu, Xiaolian Cai, Gang Ouyang, Sijia Fan, Jing Wang, Wuhan Xiao*. Zebrafish prmt7 negatively regulates antiviral response by suppressing the retinoic acid-inducible gene 1-like receptor signaling.FASEB Journal,2020,34(1):988-1000.

(27) Junji Zhu, Xing Liu, Xiaolian Cai, Gang Ouyang, Huangyuan Zha, Ziwen Zhou, Qian Liao, Jing Wang, Wuhan Xiao*. Zebrafish prmt3 negatively regulates antiviral responses. FASEB Journal, 2020, 34(8):10212-10227.

2019

(28) Junji Zhu, Dawei Zhang, Xing Liu, Guangqing Yu, Xiaolian Cai, Chenxi Xu, Fangjing Rong, Gang Ouyang, Jing Wang, Wuhan Xiao*. Zebrafish prmt5 arginine methyltransferase is essential for germ cell development.  Development, 2019, 146(20): dev179572.

(29) Guangqing Yu, Xing Liu, Jinghua Tang, Chenxi Xu, Gang Ouyang, Wuhan Xiao*. Neddylation facilitates the antiviral response in zebrafish. Frontiers in Immunology, 2019, 10: 1432.

2018

(30) Xiaolian Cai, Dawei Zhang, Jing Wang, Xing Liu, Gang Ouyang, Wuhan Xiao*. Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish. Journal of Biological Chemistry, 2018, 293(40): 15370-15380.

(31) Chenxi Xu, Xing Liu, Huangyuan Zha, Sijia Fan, Dawei Zhang, Wuhan Xiao*. A pathogen-derived effector modulates host glucose metabolism by arginine GlcNAcylation of HIF-1α protein. PLoS Pathogens, 2018, 18(8): e1007259.

2017

(32) Dawei Zhang, Jing Wang, Chi Zhou, Wuhan Xiao*. Zebrafish akt2 is essential for survival, growth, bone development, and glucose homeostasis. Mechanisms of Development, 2017, 143:42-52.

(33) Jing Wang, Dawei Zhang, Juan Du, Chi Zhou, Zhi Li, Xing Liu, Gang Ouyang, Wuhan Xiao*. Tet1 facilitates hypoxia tolerance by stabilizing the HIF-α proteins independent of its methylcytosine dioxygenase activity. Nucleic Acids Research, 2017,45(22): 12700-12714.

2016 

(34) Xing Liu, Xiaolian Cai, Dawei Zhang, Chenxi Xu, Wuhan Xiao*. Zebrafish foxo3b negatively regulates anti-viral response through suppressing the transactivity of irf3 and irf7. Journal of Immunology, 2016, 197(12): 4736-4749.

(35) Xing Liu, Xiaolian Cai, Bo Hu, Zhichao Mei, Dawei Zhang, Gang Ouyang, Jing Wang, Wei Zhang, Wuhan Xiao*. Forkhead transcription factor (FOXO3a) modulates hypoxia signaling via up-regulation of the von Hippel-Lindau gene (VHL). Journal of Biological Chemistry, 2016, 291(49): 25692-25705.

2015

(36) Xing Liu, Zhu Chen, Chenxi Xu, Xiaoqian Leng, Hong Cao, Gang Ouyang, Wuhan Xiao*. Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation. Nucleic Acids Research, 2015, 43(10): 5081-5098.

(37) Xing Liu, Zhu Chen, Gang Ouyang, Tieshan Song, Huageng Liang, Wei Liu, Wuhan Xiao*. ELL associated f actor 2 (EAF2) inhibits transforming growth factor beta signaling through a direct interaction with Smad3. Journal of Biological Chemistry, 2015, 290(43): 25933-25945.

(38) Juan Du, Dawei Zhang. Wei Zhang, Gang Ouyang, Jing Wang, Xing Liu, Sun Li, Wei Liu, Wuhan Xiao*. pVHL negatively regulates antiviral signaling by targeting MAVS for proteasomal degradation. Journal of Immunology, 2015, 195(4): 1782-1790.

(39) Zhichao Mei, Dawei Zhang, Bo Hu, Jing Wang, Xian Shen, Wuhan Xiao*. FBXO32 targets c-Myc for proteasomal degradation and inhibits c-Myc activity. Journal of Biological Chemistry, 2015, 290(26): 16202-16214.

2014

(40) Bo Hu, Wei Zhang, Xi Feng, Wei Ji, Xunwei Xie, Wuhan Xiao*. Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis, Developmental Biology, 2014, 388: 81-93.

(41) Jing Wang, Wei Zhang, Wei Ji, Xing Liu, Gang Ouyang, Wuhan Xiao*. The Von Hippel-Lindau protein suppresses androgen receptor activity. Molecular Endocrinology, 2014, 28(2): 239-248.

(42) Zhu Chen, Xing Liu, Zhichao Mei, Zhou Wang*, Wuhan Xiao*. EAF2 suppresses HIF-1a transcriptional activity by disrupting its interaction with the co-activator CBP/p300. Molecular and Cellular Biology, 2014, 34(6): 1085-1099.

(43) Wei Zhang, Wei Ji, Xing Liu, Gang Ouyang, Wuhan Xiao*. ELL inhibits E2F1 transcriptional activity by enhancing E2F1 deacetylation via recruitment of Histone Deacetylase 1. Molecular and Cellular Biology, 2014, 34(4): 765-775.

(44) Wei Ji, Jing Wang, Wei Zhang, Xing Liu, Gang Ouyang, Wuhan Xiao*. pVHL acts as a downstream target of E2F1 to suppress E2F1 activity. Biochemical Journal, 2014, 457: 185-195. 

2013

(45) Jing-xia Liu, Dawei Zhang, Xunwei Xie, Gang Ouyang, Xing Liu, Yonghua Sun, Wuhan Xiao*. Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling. Development, 2013, 140: 1067-1078.

2011

(46) Xiaoyang Wan, Bo Hu, Jing-xia Liu, Xi Feng, Wuhan Xiao*. Zebrafish mll gene is essential for hematopoiesis. Journal of Biological Chemistry, 2011, 286: 33345-33357

2009

(47) Jiangang Zhou, Xi Feng, Bing Ban, Jing-xia Liu, Zhou Wang*, Wuhan Xiao*. The elongation factor ELL (Eleven-nineteen lysine-rich leukemia) acts as a transcription factor for direct thrombospondin-1 regulation. Journal of Biological Chemistry, 2009, 284(28):19142-19152.

(48) Jing-xia Liu, Bo Hu, Yang Wang, Jianfang Gui, Wuhan Xiao*. Zebrafish eaf1 and eaf2/u19 mediate effective convergence and extension movements through the maintenance of wnt11 and wnt5 expression. Journal of Biological Chemistry, 2009, 284(24):16679-16692.