EDUCATION/TRAINING

A.Position and Employment

07/2013 – 11/2020    Assistant Professor, Shenzhen University Medical School

12/2020 – present     Associate Professor, Shenzhen University Medical School

B.Research summary

The research of my lab mainly focuses on the transcriptional and epigenetic dysregulation in cancer. We carried out a series of studies on the interactions between CREs (cis-regulatory elements) and transcriptional and epigenetic regulators in colorectal cancer (CRC), a highly prevalent malignant tumor. We have systematically investigated the mode of oncogene activation by super-enhancer (SE) and SE-associated transcription factors and epigenetic regulators in CRC; established the mechanistic link between non-coding genetic variants of susceptibility to CRC and epigenetic regulation of genes by SEs; elucidated the role of histone H3K27me3 modification and promoter DNA methylation in altering the key transcriptional features of CRC by inhibiting specific CRE activities; clarified the essential roles of these CREs and trans-regulatory factors in CRC development, stemness maintenance, invasion and metastasis, and immune dysregulation; and proposed novel therapeutic strategies targeting the regulatory machinery of SE. Our current studies continue to resolve the hierarchy of transcription regulatory network in CRC and uncover mechanisms underlying transcriptional and epigenetic control of cancer cell plasticity, drug resistance, and tumor microenvironment.

C.Representative publications (* corresponding author; # equal contribution)

1.Ying Y, Wang M, Chen Y, Li M, Ma C, Zhang J, Huang X, Jia M, Zeng J, Wang Y, Li L, Wang X, Tao Q, Shu XS^*: Zinc finger protein 280C contributes to colorectal tumorigenesis by maintaining epigenetic repression at H3K27me3-marked loci. Proc Natl Acad Sci USA 2022; 119 (22): e2120633119.

2.Chen Y^#, Ying Y^#, Ma W^#, Ma H^#, Shi L, Gao X, Jia M, Li M, Song X, Kong W, Chen W, Zheng X, Muluh TA, Wang X, Wang M, Shu XS^*. Targeting the epigenetic reader ENL inhibits super-enhancer-driven oncogenic transcription and synergizes with BET inhibition to suppress tumor progression. Cancer Research 2024; online ahead of print.

3.Ying Y^#, Wang Y^#, Huang X, Sun Y, Zhang J, Li M, Zeng J, Wang M, Xiao W, Zhong L, Xu B, Li L, Tao Q, Wang X, Shu XS^*: Oncogenic HOXB8 is driven by MYC-regulated super-enhancer and potentiates colorectal cancer invasiveness via BACH1, Oncogene 2020, 39(5):1004-1017.

4.Zhang J^#, Ying Y^#, Li M^#, Wang M, Huang X, Jia M, Zeng J, Ma C, Zhang Y, Li C, Wang X, Shu XS^*: Targeted inhibition of KDM6 histone demethylases eradicates tumor-initiating cells via enhancer reprogramming in colorectal cancer. Theranostics 2020; 10(22):10016-10030.

5.Chen Y^#, Ying Y^#, Wang M^#, Ma C, Jia M, Shi L, Wang S, Zheng X, Chen W, Shu XS^*: A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer. Cell Death & Disease 2023; 14(1): 8.

6.Shu XS^*, Zhao Y, Sun Y, Zhong L, Cheng Y, Zhang Y, Ning K, Tao Q, Wang Y^*, Ying Y^*: The epigenetic modifier PBRM1 restricts the basal activity of the innate immune system by repressing retinoic acid-inducible gene-I-like receptor signalling and is a potential prognostic biomarker for colon cancer, Journal of Pathology 2018; 244(1):36-48.

7.Hu Y^#, Shu XS^#, Yu J^#, Sun MA, Chen Z, Liu X, Fang Q, Zhang W, Hui X, Ying Y, Fu L, Lu D, Kumar R, Wang Y^*: Improving the diversity of captured full-length isoforms using a normalized single-molecule RNA-sequencing method, Communications Biology 2020; 3(1):403.

8.Liu S^#, Jiang Y^#, Yang H, Hua Z, Han Y, Zhou C, Xu S, Nie S, Xu G, Shu XS^*, Wang X^*: BIX-01294 enhances the effect of chemotherapy on colorectal cancer by inhibiting the expression of stemness genes. Biochemical and Biophysical Research Communications 2022; 590:169-176.

9.Shu XS, Li L, Ying J, Su X, Fan YC, Ng KM, Xiong L, Cheng Y, Chan AT, Tao Q: FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma, Carcinogenesis 2013; 34(9):1984-93

10.Shu XS, Li L, Tao Q: Chromatin regulators with tumor suppressor properties and their alterations in human cancers, Epigenomics 2012; 4(5):537-49

D.Research Support

National Natural Science Foundation of China

Xing-sheng Shu, PI ￥550,000

MYC-regulated distal super-enhancer promotes colorectal cancer metastasis and recurrence through activating LGR5 (01/01/2021 to 12/31/2024)

National Natural Science Foundation of China

Xing-sheng Shu, PI ￥230,000

Functional and mechanical characterization of a novel methylated 1p36 tumor suppressor gene TUSC6 in NPC and CRC (01/01/2014 to 12/31/2016)

Natural Science Foundation of Guangdong Province

Xing-sheng Shu, PI ￥100,000

Mechanism of HOXB8 activation by MYC-regulated super-enhancer in colorectal cancer metastasis (10/01/2019 to 09/30/2022)

Shenzhen Commission of Science and Innovation Program

Xing-sheng Shu, PI ￥500,000

Mechanistic studies on the transcriptional regulation of innate immune response by the chromatin remodeler PBRM1 in colon cancer (04/01/2018 to 03/30/2020)

Shenzhen University Marshall Laboratory of Biomedical Engineering Open Research Project

Xing-sheng Shu, PI ￥100,000

Epigenetic mechanisms of non-coding genomic variation-driven tumorigenesis in colorectal cancer (04/01/2023 to 03/30/2025)