Hsu Laboratory

Chih-Hung Hsu

• Principal Investigator (tenured)

      - Institute of Genetics, International School of Medicine, Zhejiang University

      - The Fourth Affiliated Hospital, Zhejiang University School of Medicine 

• Joint Faculty

      - Department of Environmental Medicine, Zhejiang University School of Medicine

Education and Experience

2011/09 - 2018/02     Research Fellow at Boston Children's Hospital/Harvard Medical School, Boston

2008/07 - 2011/08     Postdoctoral Fellow at Genomics Research Center, Academia Sinica, Taipei

2001/09 - 2006/09     Ph.D., Institute of Molecular and Cellular Biology, National Tsing Hua University, Taipei

1997/09 - 2001/06     B.S., Department of Food and Nutrition, Chinese Culture University, Taipei

Research interests

Epigenetic mechanisms serve as a vital interface that mediates gene-environment interactions and orchestrates diverse biological processes. At the Hsu Lab, we are committed to exploring how modifications on histone (EMBO J 2004; Oncogene 2012; Theranostics 2021), DNA (Cell Rep 2012), and RNA—as well as their associated modifier complexes (Nucleic Acids Res 2019; Blood Cancer Discov 2021)—respond to environmental stimuli and regulate biological processes. Among these, we particularly focus on the "RNA modification-environmental stress.” Through systematic studies on the regulatory mechanisms of RNA modifications in response to

- Physical stimuli: UV (Nature 2017), Heat (Cell Rep 2022)

- Chemical stimuli: Environmental pollutants (Natl Sci Rev 2023; Environ Sci Technol 2024)

- Biological stimuli: Microbe (Nat Commun 2022)

We have introduced the concept of “modified RNA as a robust biosensor for environmental stress (《Epitranscriptomics》2021).” This concept revises the traditional epigenetic notion that “histone and DNA modifications are the dominant regulators of gene-environment interplay”, offering a deeper understanding of the fundamental biological question of how environmental factors interact with genes to modulate biological processes.

ORCiD: https://orcid.org/0000-0001-8071-0122

Hsu Laboratory - Lab Members 

• Chih-Hung Hsu, Principal Investigator

Email: ch_hsu@zju.edu.cn

• Jiebo Lin, Postdoctral Researcher

 Email: 271065959@qq.com

• Jinfeng Liu, Postdoctral Researcher

Email: liujinfeng@zju.edu.cn

• Guankai Zhan, Postdoctral Researcher

Email: 12018355@zju.edu.cn

• Kunhui Su, PhD student

Email: 22018049@zju.edu.cn

• Siqi Sun, Master student

Email: siqi_sun@zju.edu.cn

• Hengyu Wu, Master student

Email: hengyu@zju.edu.cn

• Wenbin Tang, Master student

Email: 22318049@zju.edu.cn

• Luyao Wang, Master student

Email: littlewang@zju.edu.cn

• Ruonan Huang, Master student

Email: 1335986063@qq.com

• Yanwen Liang, Exchange student

Email: yanwen95@zju.edu.cn

Selected Publications:

●Su K#,  Lin J#, Chen J#, Wu H, Tang W,  Sun S,  Lin J, Zhan G,  Hsu CH*. Bisphenol C Induces Cardiac Developmental Defects by Disrupting m6A Homeostasis.

Environmental Science & Technology. 2024 Oct 1;58(39):17259-17269.

● Lin J^#, Zhan G^#, Liu J^#, Maimaitiyiming Y, Deng Z, Li B, Su K, Chen J, Sun S, Zheng W, Yu X, He F, Cheng X, Wang L, Shen B, Yao Z, Yang X, Zhang J, He W, Wu H, Naranmandura H, Chang KJ, Min J, Ma J, B. Mikael, Xu P*, Wang F*, Hsu CH*. YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths.

National Science Review. 2023 https://doi.org/10.1093/nsr/nwad227

_*Correspondence

^★Highlighted by EurekAlert!

● Wang L^#, Zhan G^#, Maimaitiyiming Y^#, Su Y, Lin S, Liu J, Su K, Lin J, Shen S, He W, Wang F, Chen J, Sun S, Xue Y, Gu J, Chen X, Zhang J, Zhang L, Wang Q, Chang KJ, Chiou SH, Björklund M, Naranmandura H*, Cheng X*,  Hsu CH*. m6A Modification Confers Thermal Vulnerability to HPV E7 Oncotranscripts via Reverse Regulation of its Reader Protein IGF2BP1 upon Heat Stress.

Cell Reports. 2022 Oct 25;41(4):111546.

_*Correspondence

^★Cover Article

● Chen S^#, Zhang L^#, Li M^#, Zhang Y^#, Sun M, Wang L, Lin J, Cui Y, Chen Q, Jin C, Li X, Wang B, Chen H, Zhou T*, Wang L*, Hsu CH*, Zhuo W*. Fusobacterium nucleatum Reduces METTL3-mediated m6A Modification and Contributes to Colorectal Cancer Metastasis.

Nature Communications. 2022 Mar 10;13(1):1248.

 _*Correspondence

● Liu J^#, Lin J^#, Chen J^#, Maimaitiyiming Y, Su K, Sun S, Zhan G, Hsu CH*. Bisphenol C induces developmental defects in liver and intestine through mTOR signaling in zebrafish (Danio rerio).

Chemosphere. 2023 May;322:138195. doi: 10.1016/j.chemosphere.2023.138195. 

_*Correspondence

● Maimaitiyiming Y^#, Yang T^#, Wang QQ^#,  Feng Y, Chen Z, Björklund M, Wang F, Hu C*, Hsu CH*, Naranmandura H*. Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load. 

Research. 2022 Feb 23;2022:9802969.

_*Correspondence

● Maimaitiyiming Y^#, Wang QQ^#, Yang C, Ogra Y^#, Lou Y, Smith CA, Hussain L, Shao YM, Lin J, Liu J, Wang L, Zhu Y, Lou H, Huang Y, Li X, Chang KJ, Chen H, Li H, Huang Y, Tse E, Sun J, Bu N, Chiou SH, Zhang YF, Hua HY, Ma LY, Huang P, Ge MH, Cao FL, Cheng X, Sun H, Zhou J, Vasliou V, Xu P, Jin J, Björklund M, Zhu HH, Hsu CH*, Naranmandura H*. Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins.

Blood Cancer Discovery. 2021 May 11;2(4):388-401.

_*Correspondence

^★Commented in: 'IN THE SPOTLIGHT' PML/RARA destabilization by hyperthermia: a new model for oncogenic fusion protein degradation?

Blood Cancer Discovery: 2021 Jun 10;2(4):300-301.

● Xiang Y^#, Laurent B^#, Hsu CH^#, Nachtergaele S, Lu Z, Xu C, Sheng W, Chen H, Jian O, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y. RNA m6A methylation regulates the ultraviolet-induced DNA damage response.

Nature. 2017 Mar 23;543(7646):573-576.

^#Co-first author. The order of three first authors was determined by a roll of the dice.

^★Commented in:

Nature Reviews Molecular Cell Biology: RESEARCH HIGHLIGHT. 2017 May;18(5):277.

Cancer Discovery: Research Watch. DOI: 10.1158/2159-8290.CD-RW2017-058.

Science Signaling: EDITORS' CHOICE. DOI: 10.1126/scisignal.aan2960.

F1000Prime: Article Recommendations.

● Huang Y^#, Yu SH^#, Zhen WX, Cheng T, Wang D, Lin JB, Wu YH, Wang YF, Chen Y, Shu LP, Wang Y, Sun XJ, Zhou Y, Yang F*, Hsu CH*, Xu PF*. Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2.

Theranostics. 2021 May 8;11(14):6891-6904.

_*Correspondence

^★“The Top 50 High Impact Research of Traditional Medicine" in 2021. This selection was organized by the Journal of Acupuncture and Herbal Medicine with the support of the China Association of Traditional Chinese Medicine announced on April 11, 2023.

● Chen HY, Wang ML, Laurent B, Hsu CH*, Chen MT, Lin LT, Shen J, Chang WC, Hsu J, Chen YW, Huang PI, Li CP, Ma HI, Yang YP, Hung MC, Chen CH, Lin WC, Chiou SH*. Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2. 

Theranostics. 2020 Jan 1;10(1):201-217.

_*Correspondence

● Tsai PH^#, Chien Y^#, Wang ML^#, Hsu CH^#, Laurent B^#, Chou SJ, Chang WC, Chien CS, Li HY, Lee HC, Huo TI^#, Hung JH^#, Chen CH, Chiou SH. Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network.

Nucleic Acids Research. 2019 Nov 4;47(19):10115-10133.

^#Co-first author

● Zhang J, Lee YR, Dang F, Gan W, Menon AV, Katon JM, Hsu CH, Asara JM, Tibarewal P, Leslie NR, Shi Y, Pandolfi PP, Wei W. PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage.

Cancer Discovery. 2019 Sep;9(9):1306-1323.

● Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, Zhang Y, Shulga YV, Bester AC, Fung J, Monteleone E, Wan L, Shen C, Hsu CH, Papa A, Clohessy JG, Teruya-Feldstein J, Jain S, Wu H, Matesic L, Chen RH, Wei W, Pandolfi PP. Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.

Science. 2019 May 17;364(6441).

^★Commented in:

Science: PERSPECTIVE，Restoring tumor suppression. DOI: 10.1126/science.aax5526.

Cancer Discovery: Research Watch. DOI: DOI: 10.1158/2159-8290.CD-RW2019-080.

F1000Prime: Article Recommendations.

● Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y. DNA Methylation on N6-Adenine in C. elegans.

Cell. 2015 May 7; 161(4):868-78.

^★Cover Article

^★Previewed in: An Adenine Code for DNA: A Second Life for N6-Methyladenine.

Cell. 2015 May 7; 161(4):710-3.

● Hsu CH^#, Peng KL^#, Kang ML, Chen YR, Yang YC, Tsai CH, Chu CS, Jeng YM, Chen YT, Lin FM, Huang HD, Lu YY, Teng YC, Lin ST, Lin RK, Tang FM, Lee SB, Hsu HM, Yu JC, Hsiao PW, Juan LJ. TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases.

Cell Reports. 2012 Sep 27; 2:(3):568–79.

^★Highlighted at Cell homepage from 14 to 27 September, 2012

^★Highlighted at Cell Reports homepage from 27 September to 25 October, 2012

^★Selected into Cell Reports Best of 2012.

^★Commented in Nature Reviews Cancer: RESEARCH HIGHLIGHT. 2012 Nov;12(11):738-9.

^#Co-first author

● Hsu CH, Peng KL, Jhang HC, Lin CH, Wu SY, Chiang CM, Lee SC, Yu WC, Juan LJ. The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

Oncogene. 2012 May 3;31(18):2335-49.

● Hsu CH, Chang MD, Tai KY, Yang YT, Wang PS, Chen CJ, Wang YH, Lee SC, Wu CW, Juan LJ. HCMV IE2-mediated inhibition of HAT activity downregulates p53 function.

EMBO Journal. 2004 Jun 2;23(11):2269-80.

Invited Review & Chapter: 

● Zhan G#, Liu J#, Lin J#, Chen J, Sun S, Maimaitiyiming Y*, Hsu CH*. Multifaceted Functions of RNA m6A Modification in Modulating Regulated Cell Death.

RNA Structure and Function. 2023. 539–573. 

● Su Y^#,Maimaitiyiming Y^#, Wang L^#, Cheng X*, Hsu CH*. Modulation of Phase Separation by RNA: A Glimpse on N6-Methyladenosine Modification.

Front. Cell Dev. Biol. 2021 Dec 10;9:786454. DOI: https://doi.org/10.3389/fcell.2021.786454.

_*Correspondence

● Wang L^#, Maimaitiyiming Y^#, Su K^#, Hsu CH*. RNA m6A Modification: A Mediator between Cellular Stresses and Biological Effects.

Epitranscriptomics. 2021 July pp 353-390.

_*Correspondence

● Maimaitiyiming Y, Wang QQ, Hsu CH*, Naranmandura H*. Arsenic induced epigenetic changes and relevance to treatment of acute promyelocytic leukemia and beyond. 

Toxicol Appl Pharmacol. 2020 Nov 1;406:115212.

_*Correspondence

● Liang Y^#, Zhan G^#, Chang KJ, Yang YP, Wang L, Lin J, Hsu CH*. The roles of m6A RNA modifiers in human cancer.

J Chin Med Assoc. 2020 Mar;83(3):221-226.

_*Correspondence

Other Publications: 

● Li Z^#, Xu H^#, Li J^#, Xu X^#, Wang J, Wu D, Zhang J, Liu J, Xue Z, Zhan G, Tan BCP, Chen D, Chan YS, Ng HH, Liu W, Hsu CH, Zhang D*, Shen Y*, Liang H*. Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.

Nature Communications. 2023 Jun 20;14(1):3646.

● Wang L^#, Zhang J^#, Su Y^#, Maimaitiyiming Y, Yang S, Shen Z, Lin S, Shen S, Zhan G, Wang F, Hsu CH*, Cheng X*. Distinct Roles of m5C RNA Methyltransferase NSUN2 in Major Gynecologic Cancers.. Distinct Roles of m5C RNA Methyltransferase NSUN2 in Major Gynecologic Cancers.

Frontiers in Oncology. 2022; doi: https://doi.org/10.3389/fonc.2022.786266.

_*Correspondence

● Chen HY, Lin LT, Wang ML, Laurent B, Hsu CH, Pan CM, Jiang WR, Chen PY, Ma HI, Chen YW, Huang PI, Chiou A, Chiou SH. Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3.

Sci Rep. 2017 Aug 18;7(1):8710.

● Teng YC, Lee CF, Li YS, Chen YR, Hsiao PW, Chan MY, Lin FM, Huang HD, Chen YT, Jeng YM, Hsu CH, Yan Q, Tsai MD, Juan LJ. Histone Demethylase RBP2 Promotes Lung Tumorigenesis and Cancer Metastasis.

Cancer Research. 2013 Aug 1;73(15):4711-4721.

● Tyan SW, Hsu CH, Peng KL, Chen CC, Kuo WH, Lee EY, Shew JY, Chang KJ, Juan LJ, Lee WH. Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.

PLoS ONE. 2012 Apr 13;7(4):e35128.

● Chiou SH, Yang YP, Lin JC, Hsu CH, Jhang HC, Yang YT, Lee CH, Ho LL, Hsu WM, Ku HH, Chen SJ, Chen SS, Chang MD, Wu CW, Juan LJ. The immediate early 2 protein of human cytomegalovirus mediates the apoptotic control in HCMV retinitis through upregulation of the cellular FLICE-inhibitory protein expression.

The Journal of Immunology. 2006 Nov 1;177(9):6199-206.