Group leader
LIU Zhaoqi is a Principal Investigator in CAS Key Laboratory of Genomic and Precision Medicine in Beijing Institute of Genomics, Chinese Academy of Sciences. He received his PhD degree in applied mathematics from Academy of Mathematics and Systems Science, CAS. Between 2015 and 2018, he was a Postdoctoral Research Scientist in the Department of Biomedical Informatics at Columbia University. From 2018, he was promoted to an Associate Research Scientist. He joined Beijing Institute of Genomics, CAS in October 2020, focusing on the application of data science technology in cancer genomics and pharmacogenomics.
Introduction
1) Aberrant RNA splicing
RNA splicing is a critical regulator of gene expression and mediator of proteome diversity. The most commonly reported spliceosomal mutations converged to genes including: SF3B1, U2AF1, SRSF2 and ZRSR2 (loss of function), which have been repeatedly identified in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), chronic lymphocytic leukemia as well as other myeloid neoplasms. While alterations in splicing factor genes have been suggested to promote tumorigenesis, the discovery of recurrent, high frequency change-of-function mutations in RNA splicing factors (SF) in human cancers underscored a central role for altered splicing in hematologic malignancies and solid tumors. To study the effect of SF mutations on tumorigenesis, a few challenging steps are necessary: a) Rapid identification and accurate quantification of cancer-specific aberrant RNA splicing genome-widely, b) Determining the major changes of downstream cellular processes under splicing dysregulation in a systematic way, and c) Understanding the molecular mechanisms of tumorigenesis and fast translation to potential therapeutic strategy. All these steps require extensive computational efforts. Our lab will integrate knowledges in cancer genomics, systems biology, machine learning and computer science to address these challenging difficulties.
2) Precision Medicine
Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Immunotherapies has proven to have improved objective response in tumors with high nonsynonymous mutation burden. T cell recognition of cancers relies upon presentation of tumor-specific antigens on MHC molecules, which generated by nonsynonymous mutations. However, recent studies suggested that tumor-specific alternative splicing events are far more abundant than the somatic single-nucleotide variants, and that peptides translated from intron-containing mRNAs are a unique class of neo-antigens in AML and other malignancies. In addition, spliceosome targeted therapies lead to global mis-processing of RNA and subsequent aberrant translation of intron encoded peptides. In this setting, we hypothesize that widespread accumulation of intron-encoded peptides due to RNA mis-splicing, would results in production of neo-antigens that can be targeted immunologically. We will collaborate with clinicians and pharmacists, and apply our expertise in computational biology to address this challenge.
Selected Publications
1. Qilong Li#, Peiqi Xing#, Jin Xu, Jifei Li, Liangjie Chen, Xinlu Li, Yinpeng Bai, Gang Li, Ting Xie, Luzhen Wang, Yuan Wang, Guoliang Qing, Huafeng Wang, Liang Shao, Wei Wu*, Zhaoqi Liu*, Hudan Liu*, Oncogenic DHX15 mutation enhances mitochondrial metabolism and sustains leukemia stemness, Leukemia,2026
2. Xiaomeng Zhang#, Jingru Sui#, Haoyuan Sun, Ruichao Chai, Zhaoqi Liu* & Jiguang Wang*, RBFOX3 is associated with neuronal-like phenotypic transition in recurrent glioblastoma, BMC Cancer, doi.org/10.1186/s12885-026-16597-9
3. Jingyuan Jia, Chenggang Jiang, Jindou Xie, Zhaoyi Yi, Han Di, Xuejing Li, Lei Zhou, Lu Bai, Yuwei Liu, Renlong Zhang, Lei Gong, Hongyun Wang, Zhaoqi Liu*, Weiyan Xie*, Chuzhong Li*, Xudong Xing*, Yazhuo Zhang#, SAA1 Promotes Pro-inflammatory Macrophage-mediated Bone Invasion in Silent Corticotroph Adenomas, Genomics, Proteomics & Bioinformatics， doi.org/10.1093/gpbjnl/qzag064
4.Yue Huang#, Peifang Xiao#, Lei Qin#, Li Gao#, Yang Zhao, Jingru Sui, Wenting Hu, Lei Zhou, Nan Han, Xuan Lv, Kunying Chen, Yu Liu, Hanhong Lin, Shuhong Shen, Omar Abdel-Wahab, Shaoyan Hu*, Zhaoqi Liu*(Lead contact), Qianfei Wang*, Sequence-dependent splicing dysregulation drives therapy resistance in pediatric AML, Cell Reports Medicine, 2026, Jan 20;7(1)
5.Ruixin Jiang#, Peiqi Xing#*, Jindou Xie, Gang Bai, Yuzhu Zhang, Pengcong Hou, Hao Luo, Yanni Ma, Ruixin Liu, Yang Zheng, Xiangyu Chen, Bin Jiang, Jing Huang, Yanjie Zhang, A Hunter Shain, Ming Lei, Robert L Judson-Torres, Jing Ye, Zhaoqi Liu*, Hanlin Zeng*, Spliceosomal mutation drives melanoma tumorigenesis via lineage-specific RAS activation, Science Advances, 2026 May 1;12(18):eadz8289.
6.Xiao Wen#; Xuan Lv#; Dan Guo; Nan Han; Lei Zhou; Peizhuo Wang; Zhaoqi Liu*; Deciphering splicing heterogeneity at single-cell resolution by SCSES, Nature Communications, 2025, 16(1): 9459
7.Peiqi Xing#; Pedro Bak-Gordond#; Jindou Xie#; Jian Zhang#; Zhaoqi Liu*; James L. Manley*; SUGP1 loss is the sole driver of SF3B1 hotspot mutant missplicing in cancer, Cell Reports, 2025, 44(8): 116075
8.Lei Zhou#; Yue Huang#; Yang Zhao; Dan Guo; Xiao Wen; Ruihong Xu; Xuan Lv; Song Wu; Sicheng Jing; Zhaoqi Liu*; MRAS: Master Regulator analysis of Alternative Splicing, Advanced Sciences, 2025,12(21): e2414493
9.Yue Huang#; Jing Guo#; Xueshuai Han#; Yang Zhao; Xuejing Li; Peiqi Xing; Yulou Liu; Yingxuan Sun; Song Wu; Xuan Lv; Lei Zhou; Yazhuo Zhang; Chuzhong Li*; Weiyan Xie*; Zhaoqi Liu*; Splicing diversity enhances the molecular classification of pituitary neuroendocrine tumors, Nature Communications, 2025, 16(1): 1552
10.Xinzhi Wu#; Xueshuai Han#; Haibo Zhu#; Mingxuan Li; Lei Gong; Sicheng Jing; Weiyan Xie*; Zhaoqi Liu*; Chuzhong Li*; Yazhuo Zhang*; Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors, Journal of Experimental & Clinical Cancer Research, 2025, 44(1): 27
11. Minu Seong#; Pedro Bak‐Gordon; Zhaoqi Liu; Peter D Canoll; James L Manley*; Splicing dysregulation in glioblastoma alters the function of cell migration‐related genes, Glia, 2025, 73(2): 215-270
12.Jingru Sui#; Dan Guo; Xiao Wen; Lei Zhou; Yue Huang; Haoyu Yu; Jinyu Chen; Zhaoqi Liu*; Systematic Characterization of Splicing Dysregulation in Pan Solid Tumor Transcriptome, Advanced science, 2024, 12(4): e2405626
13.Xueshuai Han#; Jingru Sui#; Kui Nie; Yang Zhao; Xuan Lv; Jindou Xie; Leonard Tan; Rex K. H. Au-Yeung; Jiao Ma; Giorgio Inghirami; Olivier Elemento; Wayne Tam* ; Zhaoqi Liu*; Tumor evolution analysis uncovered immune-escape related mutations in relapse of diffuse large B-cell lymphoma, Leukemia, 2024, 38(10): 2276-2280
14.Xueshuai Han#; Zhaoqi Liu*; Aberrant somatic hypermutation at super-enhancer drives B cell lymphoma transformation, Genomics, Proteomics & Bioinformatics, 2024, 22(4): qzae015
15. Isaac Wakiro#; Yue Huang#; Xuejing Yang; Xueqin Xie; Hanzhi Luo; Kathryn Chang; Aspen Pierson; Emily Batchelor; Yuanming Cheng; Diu TT Nguyen; Zhaoqi Liu*; Michael G Kharas*; Rbmx Regulates YTHDC1 Nuclear Condensates to Promote Nascent Transcription in Acute Myeloid Leukemia, Blood, 2024, 144(Supplement 1): 627-627
16.Kausik Regunath#; Vitalay Fomin; Zhaoqi Liu; Pingzhang Wang; Mainul Hoque; Bin Tian; Raul Rabadan*; Carol Prives*; Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types, Molecular Cancer Research, 2024, 22(6): 555-571
17.Jian Zhang#; Jindou Xie#; Ji Huang; Xiangyang Liu; Ruihong Xu; Jonas Tholen; Wojciech P.Galej; Liang Tong; James L. Manley*; Zhaoqi Liu* ; Characterization of the SF3B1–SUGP1 interface reveals how numerous cancer mutations cause mRNA missplicing, Genes & Development, 2023, 37: 1-16
18.Song Wu#; Yue Huang#; Mochen Zhang; Zheng Gong; Guoliang Wang; Xinchang Zheng; Wenting Zong; Wei Zhao; Peiqi Xing; Rujiao Li*; Zhaoqi Liu*; Yiming Bao*; ASCancer Atlas: a comprehensive knowledgebase of alternative splicing in human cancers, Nucleic Acids Research, 2023, 51(D1): D1196-D1204
19.Nan Han#; Zhaoqi Liu*；Targeting alternative splicing in cancer immunotherapy，Frontiers in Cell and Developmental Biology, 2023, 11: 1232146
20.Quanhua Mu#; Ruichao Chai#; Bo Pang; Yingxi Yang; Hanjie Liu; Zheng Zhao; Zhaoshi Bao; Dong Song; Zhihan Zhu; Mengli Yan; Biaobin Jiang; Zongchao Mo; Jihong Tang; Jason K Sa; Hee Jin Cho; Yuzhou Chang; Kaitlin Hao Yi Chan; Danson Shek Chun Loi; Sindy Sing Ting Tam; Aden Ka Yin Chan; Angela Ruohao Wu; Zhaoqi Liu; Wai Sang Poon; Ho Keung Ng; Danny Tat Ming Chan; Antonio Iavarone*; Do-Hyun Nam*; Tao Jiang*; Jiguang Wang*; Identifying predictors of glioma evolution from longitudinal sequencing, Science translational medicine, 2023, 15(716): eadh4181
21.Hao Guo#; Jin Xu#; Peiqi Xing#; Qilong Li; Donghai Wang; Chao Tang; Bruno Palhais; Juliette Roels; Jiaxu Liu; Sa Pan; Jinyan Huang; Zhaoqi Liu; Ping Zhu; Tom Taghon; Guoliang Qing; Pieter Van Vlierberghe*; Hudan Liu*; RNA helicase DHX15 exemplifies a unique dependency in acute leukemia, Haematologica, 2023, 108(8): 2029–2043
22.Jian Zhang#; Ji Huang; Ke Xu; Peiqi Xing; Yue Huang; Zhaoqi Liu; Liang Tong; James L. Manley*; DHX15 is involved in SUGP1-mediated RNA mis-splicing by mutant SF3B1 in cancer, Proceedings of the National Academy of Sciences 2022, 119 (49) : e2216712119.
23.Yen K. Lieu#*; Zhaoqi Liu;Abdullah M. Alig; Xin Weih; Alex Pensond; Jian Zhanga; Xiuli Anh; Raul Rabadand; Azra Razab; James L. Manleya*; Siddhartha Mukherjee*; SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes, Proceedings of the National Academy of Sciences 2022, 119(1): e2111703119.
24.Zhaoqi Liu#*, Raul Rabadan*；Computing the role of alternative splicing in cancer, Trends in cancer, 2021,7(4): 347-358
25.Bo Liu#; Zhaoqi Liu#; Sisi Chen; Michelle Ki; Caroline Erickson; Jorge S. Reis-Filho;Benjamin H. Durham; Qing Chang; Elisa de Stanchina; Yiwei Sun; Raul Rabadan; Omar Abdel-Wahab*; Sarat Chandarlapaty* ; Mutant SF3B1 promotes AKT and NF-kB driven mammary tumorigenesis, The Journal of Clinical Investigation, 2021, 131(1): e138315
26.Camila Prieto#; Diu Nguyen#; Zhaoqi Liu; Justin Wheat; Alexendar Perez; Saroj Gourkanti; Timothy Chou; Anthony Velleca; Thomas Rohwetter; Ersilia Barin; Arthur Chow; James Taggart; Katerina Hoskova; Meera Dhodapkar; Alexandra Schurer; Trevor S Barlowe; Ly P Vu; Christina Leslie; Ulrich Steidl; Raul Rabadan*; Michael G Kharas*; Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia, Nature Cancer, 2021, 2(7): 741-757
27.Delin Chen#; Bo Chu#; Xin Yang; Zhaoqi Liu; Ying Jin; Ning Kon; Raul Rabadan; Xuejun Jiang; Brent R. Stockwell; Wei Gu*; iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4, Nature Communications, 2021,12(1): 3644
28.Mai Sato#; Andrew Walter Liebau; Zhaoqi Liu; Lizhi Liu; Raul Rabadan; Jean Gautier*; The UVSSA complex alleviates MYC-driven transcription stress, Journal of Cell Biology, 2021, 220 (2): e201807163.
29.Zhaoqi Liu#; Ioan Filip; Karen Gomez; Dewaldt Engelbrecht; Shabnum Meer; Pooja N. Lalloo;Pareen Patel; Yvonne Perner; Junfei Zhao; Jiguang Wang; Laura Pasqualucci*; Raul Rabadan*; Pascale Willem*; Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway, Blood Cancer Discovery, 2020, 1(1): 112-125
30.Zhaoqi Liu#; Akihide Yoshimi#*; Jiguang Wang; Hana Cho; Stanley Chun-Wei Lee; Michelle Ki;Lillian Bitner; Timothy Chu; Harshal Shah; Bo Liu; Anthony R. Mato; Peter Ruvolo; Giulia Fabbri; Laura Pasqualucci; Omar Abdel-Wahab; Raul Rabadan*; Mutations in the RNA Splicing Factor SF3B1Promote Tumorigenesis through MYC Stabilization, Cancer Discovery, 2020, 10(6): 806-821
31.Zhaoqi Liu#; Jian Zhang#; Yiwei Sun; Tomin E. Perea-Chamblee; James L. Manley*; Raul Rabadan*; Pan-cancer analysis identifies mutations in SUGP1 that recapitulate mutant SF3B1 splicing dysregulation, Proceedings of the National Academy of Sciences, 2020, 117(19): 10305-10312
32.Danilo Fiore#; Luca Vincenzo Cappelli#; Paul Zumbo; Jude M Phillips; Zhaoqi Liu; Shuhua Cheng; Liron Yoffe; Paola Ghione; Federica Di Maggio; Ahmet Dogan; Inna Khodos; Elisa de Stanchina; Joseph Casano;Clarisse Kayembe; Wayne Tam; Doron Betel; Robin Foa’; Leandro Cerchietti; Raul Rabadan; Steven Horwitz; David M Weinstock; Giorgio Inghirami*; A novel JAK1 mutant breast implant-associated anaplastic large cell lymphoma patient-derived xenograft fostering pre-clinical discoveries, Cancers, 2020, 12(6): 1603
33.Luis Arnes#*; Zhaoqi Liu#; Jiguang Wang#; Carlo Maurer; Irina Sagalovskiy; Marta SanchezMartin;Nikhil Bommakanti; Diana C Garofalo; Dina A Balderes; Lori Sussel; Kenneth P Olive*; Raul Rabadan *; Comprehensive characterization of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma, Gut, 2019, 68(3): 499-511
34.Suji Han#; Hyemi Shin#; Jin-Ku Lee#; Zhaoqi Liu; Raul Rabadan; Jeongwu Lee; Jihye Shin; Cheolju Lee; Heekyoung Yang; Donggeon Kim; Sung Heon Kim; Jooyeon Kim; Jeong-Woo Oh; Doo-Sik Kong; Jung-Il Lee; Ho Jun Seol; Jung Won Choi; Hyun Ju Kang*; Do-Hyun Nam*; Secretome analysis of patient-derived GBM tumor spheres identifies midkine as a potent therapeutic target, Experimental & molecular medicine, 2019, 51(12): 1-11
35.Jian Zhang#; Abdullah M Ali; Yen K Lieu; Zhaoqi Liu; Jianchao Gao;Raul Rabadan; Azra Raza; Siddhartha Mukherjee*; James L Manley*; Disease-causing mutations in SF3B1 alter splicing by disrupting interaction with SUGP1, Molecular cell , 2019, 76(1): 82-95. e7
36.Jin-Ku Lee#; Zhaoqi Liu#; Jason K. Sa#; Sang Shin#; Jiguang Wang#; Mykola Bordyuh; Hee Jin Cho; Oliver Elliott; Timothy Chu; Seung Won Choi; Daniel I. S. Rosenbloom; In-Hee Lee; Yong Jae Shin; Hyun Ju Kang; Donggeon Kim; Sun Young Kim; Moon-Hee Sim; Jusun Kim; Taehyang Lee; Yun Jee Seo; Hyemi Shin; Mijeong Lee; Sung Heon Kim; Yong-Jun Kwon; Jeong-Woo Oh; Minsuk Song; Misuk Kim;Doo-Sik Kong; Jung Won Choi; Ho Jun Seol; Jung-Il Lee; Seung Tae Kim; Joon Oh Park; Kyoung-Mee Kim; Sang-Yong Song; Jeong-Won Lee; Hee-Cheol Kim; Jeong Eon Lee; Min Gew Choi; Sung Wook Seo; Young Mog Shim; Jae Ill Zo; Byong Chang Jeong; Yeup Yoon; Gyu Ha Ryu; Nayoung K. D. Kim; Joon Seol Bae; Woong-Yang Park; Jeongwu Lee; Roel G. W. Verhaak; Antonio Iavarone; Jeeyun Lee*; Raul Rabadan*; Do-Hyun Nam*; Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy, Nature Genetics, 2018, 50(10): 1399-1411
37. Magdolna Djurec#; Osvaldo Graña; Albert Lee; Kevin Troulé; Elisa Espinet; Lavinia Cabras; Carolina Navas; María Teresa Blasco; Laura Martín-Díaz; Miranda Burdiel; Jing Li, Zhaoqi Liu; Mireia Vallespinós; Francisco Sanchez-Bueno; Martin R Sprick; Andreas Trumpp; Bruno Sainz; Fátima Al-Shahrour; Raul Rabadan; Carmen Guerra*; Mariano Barbacid*; Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors, Proceedings of the National Academy of Sciences, 2018, 115(6) : E1147-E1156
38.Jin-Ku Lee#; Jiguang Wang#; Jason K Sa#; Erik Ladewig#; Hae-Ock Lee; In-Hee Lee; Hyun Ju Kang; Daniel S Rosenbloom; Pablo G Camara; Zhaoqi Liu; Patrick van Nieuwenhuizen; Sang Won Jung; Seung Won Choi; Junhyung Kim; Andrew Chen; Kyu-Tae Kim; Sang Shin; Yun Jee Seo; Jin-Mi Oh; Yong Jae Shin; Chul-Kee Park; Doo-Sik Kong; Ho Jun Seol; Andrew Blumberg; Jung-Il Lee; Antonio Iavarone; Woong-Yang Park*; Raul Rabadan* & Do-Hyun Nam*; Spatiotemporal genomic architecture informs precision oncology in glioblastoma, Nature Genetics, 2017, 49(4), 594-599
39.Jiguang Wang#; Emanuela Cazzato; Erik Ladewig; Veronique Frattini; Daniel I S Rosenbloom; Sakellarios Zairis; Francesco Abate; Zhaoqi Liu; Oliver Elliott; Yong-Jae Shin; Jin-Ku Lee; In-Hee Lee; Woong-Yang Park; Marica Eoli; Andrew J Blumberg; Anna Lasorella; Do-Hyun Nam*; Gaetano Finocchiaro*; Antonio Iavarone *; Raul Rabadan*; Clonal evolution of glioblastoma under therapy, Nature Genetics, 2016, 48(7): 768-776
41.Xuemei Ning#; Zhaoqi Liu; Shihua Zhang*; Local community extraction in directed networks, Physica A: Statistical Mechanics and its Applications, 2016, 452: 258-265
41.Zhaoqi Liu#; Shihua Zhang*; Tumor characterization and stratification by integrated molecular profiles reveals essential pan-cancer features, BMC genomics, 2015,16: 1-12
42.Meng Zou#; Zhaoqi Liu; Xiang-Sun Zhang; Yong Wang*; NCC-AUC: an AUC optimization method to identify multi-biomarker panel for cancer prognosis from genomic and clinical data, Bioinformatics, 2015, 31(20): 3330-3338
43.Xiaofeng Dai#; Zhaoqi Liu; Shihua Zhang*; Over-expression of EPS15 is a favorable prognostic factor in breast cancer, Molecular bioSystems, 2015, 11(11): 2978-2985
