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Chunliang Li, PhD
Chunliang Li, PhD


BS – Central China Normal University
PhD – Shanghai Institute of Biological Sciences, Chinese Academy of Sciences

Honors & Awards

  • 2023 American Cancer Society Research Scholar Award
  • 2021  V-foundation Scholar Award

Research Interests

My long-term research interests focus on understanding how the non-coding genome and dysregulated transcription contribute to cancer and developing innovative strategies targeting the underlying molecular mechanisms. Current research is mainly directed to MLL-rearranged (MLL-r) human leukemia cell lines, patient-derived xenografts (PDXs), and engineered mouse tumor models. MLL/KMT2A MLLr occurs in ~10% of human leukemias, including >80% of infant leukemia, ~5-10% of B-ALL, and ~10% of AMLs, that exhibit particularly poor clinical outcomes. Despite significantly increased overall survival rates in most subtypes of ALL and AML following extensive chemotherapy, alternative therapeutic strategies for MLL-r leukemias are urgently needed. I am dedicated to utilizing integrative approaches to decode the function of non-coding regions of the human cancer genome that are largely unexplored. Using cutting-edge technologies and multidisciplinary approaches including genetic and epigenomic CRISPR editing, comprehensive screens, and the auxin-induced protein degradation system, my laboratory actively investigates the functions of noncoding segments involved in gene transcription, chromatin architecture, and maintenance of chromatin accessibility. I anticipate these efforts will shed light on understanding how temporal and spatial gene regulation is precisely controlled and provide insights into alternative leukemia therapy.

Selected Publications

Zhang M, Hyle J, Chen X, Xin Y, Jin Y, Zhang J, Yang X, Chen X, Wright S, Liu Z, Rosikiewicz W, Xu B, He L, Liu H, Ping N, Wu D, Wen F, Li C, Xu P. (co-corresponding author).RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9. Genome Biol Jan 12;25(1):16, 2024. doi: 10.1186/s13059-023-03149-8. PMID: 38216972 

Wright S, Zhao X, Rosikiewicz W, Mryncza S, Hyle J, Qi W, Liu Z, Yi S, Cheng Y, Xu B, Li C. Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens. Nat Commun Nov 28;14(1):7464, 2023. doi: 10.1038/s41467-023-43264-5. PMID: 38016946

Bloom M, Oak N, Baskin-Doerfler R, Feng R, Iacobucci I, Baviskar P, Zhao X, Stroh AN, Li C, Ozark P, Tillman H, Li Y, Verbist KC, Albeituni S, Scott DC, King MT, McKinney Freeman SL, Weiss MJ, Yang JJ, Nichols KE. ETV6 Represses Inflammatory Response Genes and Regulates HSPC Function During Stress Hematopoiesis in Mice. Blood Adv Jul 31;bloodadvances.2022009313, 2023. doi: 10.1182/bloodadvances.2022009313. Online ahead of print. PMID: 37522715

Wang H, Pan X, Xiang X, Zhang Y, Chen J, Wen S, Wang J, Gao R, Yang J, Zhi Y, Wen S, Zheng Y, Li T, Ai H, He X, Lu Y, Zhu Y, Li C*, Chen Y*, Shi G*. CRISPR screen identifies the role of RBBP8 in mediating unfolded protein response induced liver damage through regulating protein synthesis. Cell Death Dis Aug 18;14(8):531, 2023. doi: 10.1038/s41419-023-06046-x. PMID: 37591836 (*Co-corresponding authors)

Wright S, Hu J, Wang H, Hyle J, Zhang Y, Du G, Konopleva MY, Kornblau SM, Djekidel MN, Rosikiewicz W, Xu B, Lu R, Yang JJ, Li C. Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens. Proc Natl Acad Sci U S A Apr 18;120(16):e2220134120, 2023. doi: 10.1073/pnas.2220134120. PMID: 37036970 

Hyle J, Djekidel MN, Williams J, Wright S, Shao Y, Xu B, Li C. Auxin-inducible degron 2 system deciphers functions of CTCF domains in transcriptional regulation. Genome Biol Jan 26;24(1):14, 2023. doi: 10.1186/s13059-022-02843-3. PMID: 36698211

Kamens JL, Dang J, Shaw TI, Gout AM, Newman S, Hagiwara K, Smith AMR, Obermayer AN, Aldridge S, Ma J, Zhang Y, Wu G, Leventaki V, Santiago T, Raimondi S, Nakitandwe J, Pappo A, Li C, Zhang J, Gruber TA. Malignant Progression of an Ancestral Bone Marrow Clone Harboring a CIC-NUTM2A Fusion in Isolated Myeloid Sarcoma. Mol Cancer Res Jan 13:OF1-OF6, 2023. doi: 10.1158/1541-7786. MCR-22-0544. Online ahead of print. PMID: 36637394

Feng R, Mayuranathan T, Huang P, Doerfler PA, Li Y, Yao Y, Zhang J, Palmer LE, Mayberry K, Christakopoulos GE, Xu P, Li C, Cheng Y, Blobel GA, Simon MC, Weiss MJ. Activation of γ-globin expression by hypoxia-inducible factor 1α. Nature Oct 12, 2022. doi: 10.1038/s41586-022-05312-w. Online ahead of print. PMID: 36224385

Bergeron BP, Diedrich JD, Zhang Y, Barnett KR, Dong Q, Ferguson DC, Autry RJ, Yang W, Hansen BS, Smith C, Crews KR, Fan Y, Pui CH, Pruett-Miller SM, Relling MV, Yang JJ, Li C, Evans WE, Savic D. Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia. Leukemia Oct;36(10):2374-2383, 2022. doi: 10.1038/s41375-022-01685-z. Epub 2022 Aug 26. PMID: 36028659

Sapkota Y, Ehrhardt MJ, Qin N, Wang Z, Liu Q, Qiu W, Shelton K, Shao Y, Plyler E, Mulder HL, Easton J, Michael JR, Burridge PW, Wang X, Wilson CL, Jefferies JL, Chow EJ, Oeffinger KC, Morton LM, Li C, Yang JJ, Zhang J, Bhatia S, Mulrooney DA, Hudson MM, Robison LL, Armstrong GT, Yasui Y. A novel locus on 6p21.2 for cancer treatment-induced cardiac dysfunction among childhood cancer survivors. J Natl Cancer Inst 2022 Jun 14:djac115. doi: 10.1093/jnci/djac115. Online ahead of print. PMID: 35698272

Zhao X, Qian M, Goodings C, Zhang Y, Yang W, Wang P, Xu B, Tian C, Pui CH, Hunger SP, Raetz EA, Devidas M, Relling MV, Loh ML, Savic D, Li C*, Yang JJ*. Molecular mechanisms of ARID5B-mediated genetic susceptibility to acute lymphoblastic leukemia. J Natl Cancer Inst May 16:djac101, 2022. doi: 10.1093/jnci/djac101. Online ahead of print. PMID: 35575404 (*co-corresponding author)

Dietlein F, Wang AB, Fagre C, Tang A, Besselink NJM, Cuppen E, Li C, Sunyaev SR, Neal JT, Van Allen EM. Genome-wide analysis of somatic noncoding mutation patterns in cancer. Science Apr 8;376(6589):eabg5601, 2022. doi: 10.1126/science.abg5601. Epub 2022 Apr 8.PMID: 35389777

Aryal S, Zhang Y, Wren S, Li C*, Lu R*. Molecular Regulators of HOXA9 in Acute Myeloid Leukemia. FEBS J Nov 7, 2021. doi: 10.1111/febs.16268. Online ahead of print. PMID: 34743404 Review. (* co-corresponding authors)

Zhao L, Zhang P, Galbo PM, Zhou X, Aryal S, Qiu S, Zhang H, Zhou Y, Li C, Zheng D, Bhatia R, Lu R. Transcription Factor MEF2D is Required for the Maintenance of MLL-rearranged Acute Myeloid Leukemia. Blood Adv Oct 1:bloodadvances.2021004469, 2021. doi: 10.1182/bloodadvances.2021004469. Online ahead of print. PMID: 34597364

Xu B, Wang H, Wright S, Hyle J, Zhang Y, Shao Y, Niu M, Fan Y, Rosikiewicz W, Djekidel MN, Peng J, Lu R, Li C. Acute depletion of CTCF rewires genome-wide chromatin accessibility. Genome Biol Aug 24;22(1):244, 2021. doi: 10.1186/s13059-021-02466-0. PMID: 34429148

Li Y, Yang W, Devidas M, Winter SS, Kesserwan C, Yang W, Dunsmore KP, Smith C, Qian M, Zhao X, Zhang R, Gastier-Foster JM, Raetz EA, Carroll WL, Li C, Liu PP, Rabin KR, Sanda T, Mullighan CG, Nichols KE, Evans WE, Pui CH, Hunger SP, Teachey DT, Relling MV, Loh ML, Yang JJ. Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia. J Clin Invest Jun 24:147898, 2021. doi: 10.1172/JCI147898. Online ahead of print.

Zong X, Hao X, Xu B, Crawford JC, Wright S, Li J, Zhang Y, Bai L, He M, Jiang M, Fan Y, Connelly JP, Pruett-Miller SM, Berns H, Janke L, Li C*, Feng Y*. Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity. J Exp Med Aug 2;218(8):e20202415, 2021. doi: 10.1084/jem.20202415. Epub Jun 4, 2021. PMID: 34086055 (*co-corresponding author)

Williams J, Xu B, Putnam D, Thrasher A, Li C, Yang J, Chen X. MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors. Genome Biol Jan 19;22(1):24,  2021. doi: 10.1186/s13059-020-02220-y. PMID: 33461601

Zhou X, Wang J, Patel J, Valentine M, Shao Y, Newman S, Sioson E, Tian L, Liu Y, Brady SW, Flasch D, Ma X, Liu Y, Paul R, Edmonson MN, Rusch MC, Li C, Baker SJ, Easton J, Zhang J. Exploration of Coding and Non-coding Variants in Cancer Using GenomePaint. Cancer Cell Jan 11;39(1):83-95.e4, 2021. PMID: 33434514. doi: 10.1016/j.ccell.2020.12.011

Peng Xu, Daniel C Scott, Beisi Xu, Yu Yao, Ruopeng Feng , Li Cheng, Kalin Mayberry, Wenjian Bi, Lance E Palmer , Moeko T King, Hong Wang, Yuxin Li, Yiping Fan, Arno F Alpi, Chunliang Li, Junmin Peng, James Papizan, Shondra M Pruett-Miller, Ria Spallek, Florian Bassermann, Yong Cheng, Brenda A Schulman, Mitchell J Weiss. FBXO11-Mediated Proteolysis of BAHD1 Relieves PRC2-dependent Transcriptional Repression in Erythropoiesis. Blood Nov 6;blood.2020007809, 2020. doi: 10.1182/blood.2020007809. Online ahead of print. PMID: 33156908

Hao Zhang , Yang Zhang, Xinyue Zhou, Shaela Wright, Judith Hyle, Lianzhong Zhao, Jie An, Xujie Zhao, Ying Shao, Beisi Xu, Hyeong-Min Lee, Taosheng Chen, Yang Zhou, Xiang Chen, Rui Lu, Chunliang Li. Functional interrogation of HOXA9 regulome in MLLr leukemia via reporter-based CRISPR/Cas9 screen. Elife Oct 1;9:e57858, 2020. Online ahead of print. PMID: 33001025 doi: 10.7554/eLife.57858 

Liu Y*, Li C*, Shen S*, Chen X, Szlachta K, Edmonson MN, Shao Y, Ma X, Hyle J, Wright S, Ju B, Rusch MC, Liu Y, Li B, Macias M, Tian L, Easton J, Qian M, Yang JJ, Hu S, Look AT, Zhang J. Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X. Nat Genet Jul 6, 2020. doi: 10.1038/s41588-020-0659-5. Online ahead of print. PMID: 32632335
*equal contribution

Mondal B, Jin H, Kallappagoudar S, Sedkov Y, Martinez T, Sentmanat MF, Poet GJ, Li C, Fan Y, Pruett-Miller SM, Herz HM. The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression program to control neurite outgrowth. Elife Apr 16, 2020;9. pii: e57519. doi: 10.7554/eLife.57519.

Zhang Y, Hyle J, Wright S, Shao Y, Zhao X, Zhang H, Li C. A cis-element within the ARF locus mediates repression of p16 INK4A expression via long-range chromatin interactions. Proc Natl Acad Sci U S A Dec 9, 2019. pii: 201909720. doi: 10.1073/pnas.1909720116. [Epub ahead of print] PMID 31818950

Vijayakrishnan J, Qian M, Studd JB, Yang W, Kinnersley B, Law PJ, Broderick P, Raetz EA, Allan J, Pui CH, Vora A, Evans WE, Moorman A, Yeoh A, Yang W, Li C, Bartram CR, Mullighan CG, Zimmerman M, Hunger SP, Schrappe M, Relling MV, Stanulla M, Loh ML, Houlston RS, Yang JJ. Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk. Nat Commun Nov 25;10(1):5348, 2019. doi: 10.1038/s41467-019-13069-6. PMID 31767839 

Xu H, Zhao X, Bhojwani D, E S, Goodings C, Zhang H, Seibel NL, Yang W, Li C, Carroll WL, Evans WE, Yang JJ. ARID5B Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia. Clin Cancer Res Oct 1, 2019. doi: 10.1158/1078-0432.CCR-19-0190. [Epub ahead of print] PMID 31573954

Hyle J, Zhang Y, Wright S, Xu B, Shao Y, Easton J, Tian L, Feng R, Xu P, Li C. Acute depletion of CTCF directly affects MYC regulation through loss of enhancer-promoter looping. Nucleic Acids Res  Jul 26;47(13):6699-6713, 2019. doi: 10.1093/nar/gkz462.

Wang H, Diaz AK, Shaw TI, Li Y, Niu M, Cho JH, Paugh BS, Zhang Y, Sifford J, Bai B, Wu Z, Tan H, Zhou S, Hover LD, Tillman HS, Shirinifard A, Thiagarajan S, Sablauer A, Pagala V, High AA, Wang X, Li C, Baker SJ, Peng J. Deep multiomics profiling of brain tumors identifies signaling networks downstream of cancer driver genes. Nat Commun Aug 16;10(1):3718, 2019. doi: 10.1038/s41467-019-11661-4.

Tian L, Shao Y, Nance S, Dang J, Xu B, Ma X, Li Y, Ju B, Dong L, Newman S, Zhou X, Schreiner P, Tseng E, Hon T, Ashby M, Li C, Easton J, Gruber TA, Zhang J. Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia. Nat Commun Jun 26;10(1):2789, 2019. doi: 10.1038/s41467-019-10637-8. PMID: 31243274

Hu D, Jablonowski C, Cheng PH, AlTahan A, Li C, Wang Y, Palmer L, Lan C, Sun B, Abu-Zaid A, Fan Y, Brimble M, Gamboa NT, Kumbhar RC, Yanishevski D, Miller KM, Kang G, Zambetti GP, Chen T, Yan Q, Davidoff AM, Yang J. KDM5A Regulates a Translational Program that Controls p53 Protein Expression. iScience Nov 30;9:84-100, 2018. doi: 10.1016/j.isci.2018.10.012. Epub 2018 Oct 17. PMID: 30388705

Caggia S, Chunduri H, Millena AC, Perkins JN, Venugopal SV, Vo BT, Li C, Tu Y, Khan SA. Novel role of Giα2 in cell migration: Downstream of PI3-kinase-AKT and Rac1 in prostate cancer cells. J Cell Physiol Aug 4, 2018. doi: 10.1002/jcp.26894. [Epub ahead of print] PMID: 30078221

Vo BT, Kwon JA, Li C, Finkelstein D, Xu B, Orr BA, Sherr CJ, Roussel MF. Mouse medulloblastoma driven by CRISPR activation of cellular Myc. Sci Rep Jun 7;8(1):8733, 2018. doi: 10.1038/s41598-018-24956-1. PMID: 29880921

Li Y, Guo X, Hu C, Du Y, Guo C, Di Wang, Zhao W, Huang G, Li C, Lu Q, Lai R, Xu T, Qi X. Type I IFN operates pyroptosis and necroptosis during multidrug-resistant A. baumannii infection. Cell Death Differ Jul;25(7):1304-1318, 2018. doi: 10.1038/s41418-017-0041-z. Epub 2018 Jan 19. PMID: 29352265

van Oosterwijk JG*, Li C*, Yang X, Opferman JT, Sherr CJ. Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects of Arf tumor suppressor-deficient mice. Proc Natl Acad Sci U S A 114(28):7420-7425, 2017. (*equal contribution) pii: 201707292 doi: 10.1073/pnas.1707292114 [Epub ahead of print] PMID 28652370

Hu S, Qian M, Zhang H, Guo Y, Yang J, Zhao X, He H, Lu J, Pan J, Chang M, Du G, Lin TN, Kham SK, Quah TC, Ariffin H, Tan AM, Cheng Y, Li C, Yeoh AE, Pui CH, Skanderup AJ, Yang JJ. Whole-genome non-coding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations. Blood 129(24):3264-3268, 2017.

Vo BT*, Li C*, Morgan MA, Theurillat I, Finkelstein D, Wright S, Hyle J, Smith SM, Fan Y, Wang YD, Wu G, Orr BA, Northcott PA, Shilatifard A, Sherr CJ, Roussel MF. Inactivation of Ezh2 Upregulates Gfi1 and Drives Aggressive Myc-Driven Group 3 Medulloblastoma. Cell Rep 18(12):2907-2917, 2017. *Equal contributors

Zhu Z, Li C, Zeng Y, Ding J, Qu Z, Gu J, Ge L, Tang F, Huang X, Zhou C, Wang P, Zheng D, Jin Y. PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs. Cell Stem Cell Nov 17, 2016. Epub ahead of print. PMID: 27939217

Traxler EA, Yao Y, Wang YD, Woodard KJ, Kurita R, Nakamura Y, Hughes JR, Hardison RC, Blobel GA, Li C, Weiss MJ. A genome-editing strategy to treat beta-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med 22(9):987-990, 2016.

Li C, Qi R, Singleterry R, Hyle J, Balch A, Li X, Sublett J, Berns H, Valentine M, Valentine V, Sherr CJ. Simultaneous gene editing by injection of mRNAs encoding transcription activator-like effector nucleases (TALENS) into Mouse Zygotes. Mol Cell Biol 34(9):1649-58, 2014. doi: 10.1128/MCB.00023-14. Epub 2014 Feb 24. Cover and spotlight commentary.

Li C, Finkelstein D, Sherr CJ. Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells. Proc Natl Acad Sci USA 110(12):E1112-1121, 2013.

Ma Y, Li C, Gu J, Tang F, Li C, Li P, Ping P, Yang S, Li Z, Jin Y. Aberrant gene expression profiles in pluripotent stem cells induced from fibroblasts of a Klinefelter syndrome patient.J Biol Chem 287(46):38970-38979, 2012.

Ma Y*, Gu J*, Li C, Wei X, Tang F, Shi G, Jiang J, Kuang Y, Li J, Wang Z, Xie X, Jin Y. Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells. Stem Cell Res Ther 3(4):29, 2012. *Equal contribution.

Amps K, et al. The International Stem Cell Initiative Group. Screening a large, ethnically diverse population of human embryonic stem cells identifies a chromosome 20 minimal amplicon that confers a growth advantage. Nat Biotechnol 29(12):1132-1144, 2011.

Li L, Sun L, Gao F, Yang Y, Li C, Gu J, Jiang J, Wei Z, Tang F, Yang A, Lu R, Kwon SW, Zhao Y, Li J, Jin Y. Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. Proc Natl Acad Sci USA 107(4):1402-1407, 2010.

Li C, Yang Y, Lu X, Sun Y, Gu J, Feng Y, Jin Y. Efficient derivation of Chinese human embryonic stem cell lines from frozen embryos. In Vitro Cell Dev Biol Anim 46(3-4):186-191, 2010.

Fang H*, Yang Y*, Li C, Fu S, Yang Z, Jin G, Zhang J, Jin Y. Transcriptome analysis of early organogenesis in human embryos. Dev Cell 19(1):174-184, 2010. *Equal contribution.

Li C*, Yu H*, Ma Y, Jiang H, Jiang J, Gu J, Shi G, Yang Y, Li J, Jin Y. Germline-competent mouse-induced pluripotent stem cell lines generated on human fibroblasts without exogenous leukemia inhibitory factor. PloS ONE 4(8):e6724, 2009. *Equal contribution.

Li C*, Zhou J*, Shi G, Ma Y, Yang Y, Gu J, Yu H, Chen F, Jin Y. Pluripotency can be rapidly and efficiently induced in human amniotic fluid-derived cells. Hum Mol Genet 18(22):4340-4349, 2009. *Equal contribution.

Li C*, Yang Y*, Gu J, Jin Y. The unique molecular signature of undifferentiated rat embryonic stem-like cells and its comparison with the mouse and human. Cell Research 19:173-186, 2009. *Equal contribution.

Xu H, Wang W, Li C, Yang A, Wang B, Jin Y. WWP2 promotes degradation of transcription factor OCT4 through 26S proteasome in human pluripotent stem cells. Cell Research 19:561–573, 2009.

Shu R, Zhang F, Liu X-S, Li C, Wang L, Tai Y, Wu X, Yang X, Liao X, Gu M, Huang L, Wang Z. Target deletion of the cytoskeleton-associated protein palladin does not impair neurite outgrowth in mice.PLoS ONE 4(9):e6916, 2009.

Guan Y, Cui L, Gong Y, Xia C, Jing N, Wu Y, Li C, Jiang H, Zhong X, Wu X, Li W, Xu G. Transplantation of marrow stromal cells to rescue retinal cells in SI-induced retinal degeneration in rats (letter). Cell Research 18, S152-S152, 2008.

Hu Y, Hirasawa R, Hu J, Hata K, Li C, Jin Y, Chen T, Li E, Rigolet M, Viegas-Péquignot E, Sasaki H, Xu G. Regulation of DNA methylation activity through Dnmt3L promoter methylation by Dnmt3 enzymes in embryonic development. Hum Mol Genet 17(17):2654-2664, 2008.

Sun B, Yang A, Feng Y, Sun Y, Zhu Y, Zhang Y, Jiang H, Li C, Gao F, Zhang Z, Wang W, Kong X, Jin G, Fu S, Jin Y. Temporal and parental-specific expression of imprinted genes in a newly derived Chinese human embryonic stem cell line and embryoid bodies. Hum Mol Genet 15(1):65-75, 2006.

Du C, Zhang Q, Li C, Miao D, Gui J. Induction of apoptosis in a carp leucocyte cell line infected with turbot (Scophthalmus maximus L.) rhabdovirus. Virus Research 101:119-126, 2004.

Last update: January 2024