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Li, Hui

Hui Li

Primary Appointment

Pathology

Contact Information

345 Crispell Drive
Charlottesville, VA 22908
Telephone: 434-982-6680
Fax: 434-243-7244
Email: hl9r@virginia.edu
Website: http://lilab.medicine.virginia.edu

Research Interests

Gene regulation in cancer, RNA processing; Epigenetic modification; Stem cell and development

Research Description

One of the central paradigms is that genes are located in isolated zones, minding their own business (making their own RNAs and proteins) and don?t usually cross talk with each other, except in pathological situations. For example, one of the hallmarks in cancer is DNA rearrangement, which results in the fusion of two separate genes. These gene fusion products often play critical roles in cancer development. Traditionally, they are thought to be the sole product of DNA rearrangement and therefore unique to cancer. This belief forms the basis for many cancer diagnostic and therapeutic approaches. Recently, we discovered two mechanisms that could generate fusion products without DNA rearrangement. One of the process is called ?RNA trans-splicing?, whereby two separate RNAs can be spliced together and generate a fusion RNA, which then can be translated into a fusion protein. The other process involves two neighboring genes transcribing in the same direction, ?cis-Splicing of Adjacent Genes (cis-SAGe). Our work on RNA trans-splicing and intergenic cis-splicing have posed a challenge to the traditional views and helped open a new paradigm for intergenic splicing processes that generate gene products in normal physiological conditions: even in the absence of physically ?touching? each other, genes do send messages (messenger RNA) that can be mingled together. These mechanisms may also be ways to expand out functional genome, and explaining the enigma that human and mouse, even worm share a similar number of genes. Our long-term goals are to understand the scope of these phenomena, the physiological functions of these ?intergenic splicing? process and their implications in both normal development and in cancer. We are using a wide range of approaches ranging from state-of-art bioinformatic pipeline to modified CRISPR/CAS9 systems. Another direction we are taking is more translational. Oncogene addiction is a principle important for basic understanding of tumorigenesis and cancer therapy. The challenge is to find such key oncogenes. Even though large sets of genome and transcriptome data are available to facilitate such discovery, true signals are often buried in a large number of passenger events. On the other hand, we know that a key oncogene could be dysregulated by different mechanisms in different cancer types. However this knowledge is usually accumulated through years of study and often involves different labs working on different cancer. Our strategy is to use this concept proactively to find key oncogenes that cancer cells become addicted to. Our strategy startes from pediatric tumors with relatively simple genomic landscape, find a key gene fusion, and extend to adult tumors. We have found a novel oncogene and proved its critical role in gliblastoma.

Selected Publications

Xie R, Chen X, Chen Z, Huang M, Dong W, Gu P, Zhang J, Zhou Q, Dong W, Han J, Wang X, Li H, Huang J, Lin T, Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM., 2019; Cancer letters. 449() 31-44 PMID: 30742945 |

Chen Z, Chen X, Xie R, Huang M, Dong W, Han J, Zhang J, Zhou Q, Li H, Huang J, Lin T, DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression., 2019; Molecular therapy : the journal of the American Society of Gene Therapy. 27(2) 326-341 PMID: 30660488 |

Chwalenia K, Qin F, Singh S, Li H, A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes., 2018; Nucleic acids research. 47(4) e24 PMID: 30590765 | PMCID: PMC6393300

Parameswaran S, Vizeacoumar FS, Kalyanasundaram Bhanumathy K, Qin F, Islam MF, Toosi BM, Cunningham CE, Mousseau DD, Uppalapati MC, Stirling PC, Wu Y, Bonham K, Freywald A, Li H, Vizeacoumar FJ, Molecular characterization of an MLL1 fusion and its role in chromosomal instability., 2018; Molecular oncology. 13(2) 422-440 PMID: 30548174 | PMCID: PMC6360371

Xie Z, Tang Y, Su X, Cao J, Zhang Y, Li H, PAX3-FOXO1 escapes miR-495 regulation during muscle differentiation., 2018; RNA biology. 16(1) 144-153 PMID: 30593263 | PMCID: PMC6380322

Wu P, Yang S, Singh S, Qin F, Kumar S, Wang L, Ma D, Li H, The Landscape and Implications of Chimeric RNAs in Cervical Cancer., 2018; EBioMedicine. 37() 158-167 PMID: 30389505 | PMCID: PMC6286271

Elfman J, Li H, Chimeric RNA in Cancer and Stem Cell Differentiation., 2018; Stem cells international. 2018() 3178789 PMID: 30510584 | PMCID: PMC6230395

Chen C, He W, Huang J, Wang B, Li H, Cai Q, Su F, Bi J, Liu H, Zhang B, Jiang N, Zhong G, Zhao Y, Dong W, Lin T, LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment., 2018; Nature communications. 9(1) 3826 PMID: 30237493 | PMCID: PMC6148066

Xie Z, Jia Y, Li H, Studying Protein-Protein Interactions by Biotin AP-Tagged Pulldown and LTQ-Orbitrap Mass Spectrometry., 2017; Methods in molecular biology (Clifton, N.J.). 1647() 129-138 PMID: 28808999 |

Jia Y, Xie Z, Li H, Intergenically Spliced Chimeric RNAs in Cancer., 2017; Trends in cancer. 2(9) 475-484 PMID: 28210711 | PMCID: PMC5305119

Huang R, Kumar S, Li H, Absence of Correlation between Chimeric RNA and Aging., 2017; Genes. 8(12) PMID: 29240691 | PMCID: PMC5748704

Xie Z, Li H, Fusion RNA profiling provides hints on cell of origin of mysterious tumor., 2017; Molecular & cellular oncology. 4(1) e1263714 PMID: 28197537 | PMCID: PMC5287003

Chwalenia K, Qin F, Singh S, Tangtrongstittikul P, Li H, Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA., 2017; Genes. 8(11) PMID: 29165374 | PMCID: PMC5704251

Qin F, Zhang Y, Liu J, Li H, SLC45A3-ELK4 functions as a long non-coding chimeric RNA., 2017; Cancer letters. 404() 53-61 PMID: 28716526 |

Chwalenia K, Facemire L, Li H, Chimeric RNAs in cancer and normal physiology., 2017; Wiley interdisciplinary reviews. RNA. () PMID: 28589684 |

Tang Y, Qin F, Liu A, Li H, Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells., 2017; Oncotarget. 8(19) 31415-31423 PMID: 28415823 | PMCID: PMC5458218

Li Z, Qin F, Li H, Chimeric RNAs and their implications in cancer., 2017; Current opinion in genetics & development. 48() 36-43 PMID: 29100211 |

Kumar S, Li H, In Silico Design of Anticancer Peptides., 2017; Methods in molecular biology (Clifton, N.J.). 1647() 245-254 PMID: 28809008 |

Qin F, Song Z, Chang M, Song Y, Frierson H, Li H, Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer., 2016; Cancer letters. 380(1) 39-46 PMID: 27322736 |

Qin F, Song Y, Zhang Y, Facemire L, Frierson H, Li H, Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA., 2016; PloS one. 11(3) e0150382 PMID: 26938874 | PMCID: PMC4777538

Kumar S, Vo AD, Qin F, Li H, Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data., 2016; Scientific reports. 6() 21597 PMID: 26862001 | PMCID: PMC4748267

Babiceanu M, Qin F, Xie Z, Jia Y, Lopez K, Janus N, Facemire L, Kumar S, Pang Y, Qi Y, Lazar IM, Li H, Recurrent chimeric fusion RNAs in non-cancer tissues and cells., 2016; Nucleic acids research. 44(6) 2859-72 PMID: 26837576 | PMCID: PMC4824105

Xie Z, Babiceanu M, Kumar S, Jia Y, Qin F, Barr FG, Li H, Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma., 2016; Proceedings of the National Academy of Sciences of the United States of America. 113(46) 13126-13131 PMID: 27799565 | PMCID: PMC5135356

Kumar S, Razzaq SK, Vo AD, Gautam M, Li H, Identifying fusion transcripts using next generation sequencing., 2016; Wiley interdisciplinary reviews. RNA. 7(6) 811-823 PMID: 27485475 | PMCID: PMC5065767

Pires ES, D'Souza RS, Needham MA, Herr AK, Jazaeri AA, Li H, Stoler MH, Anderson-Knapp KL, Thomas T, Mandal A, Gougeon A, Flickinger CJ, Bruns DE, Pollok BA, Herr JC, Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors., 2015; Oncotarget. 6(30) 30194-211 PMID: 26327203 | PMCID: PMC4745790

Qin F, Song Z, Babiceanu M, Song Y, Facemire L, Singh R, Adli M, Li H, Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells., 2015; PLoS genetics. 11(2) e1005001 PMID: 25658338 | PMCID: PMC4450057

Jividen K, Li H, Chimeric RNAs generated by intergenic splicing in normal and cancer cells., 2014; Genes, chromosomes & cancer. () PMID: 25131334 |

Yuan H, Qin F, Movassagh M, Park H, Golden W, Xie Z, Zhang P, Sklar J, Li H, A chimeric RNA characteristic of rhabdomyosarcoma in normal myogenesis process., 2013; Cancer discovery. 3(12) 1394-403 PMID: 24089019 |

Zhang Y, Gong M, Yuan H, Park HG, Frierson HF, Li H, Chimeric Transcript Generated by cis-Splicing of Adjacent Genes Regulates Prostate Cancer Cell Proliferation., 2012; Cancer discovery. 2(7) 598-607 PMID: 22719019 |

Jazaeri AA, Bryant JL, Park H, Li H, Dahiya N, Stoler MH, Ferriss JS, Dutta A, Molecular requirements for transformation of fallopian tube epithelial cells into serous carcinoma., 2011; Neoplasia (New York, N.Y.). 13(10) 899-911 PMID: 22028616 | PMCID: PMC3201567

Li H, Wang J, Ma X, Sklar J, Gene fusions and RNA trans-splicing in normal and neoplastic human cells., 2009; Cell cycle (Georgetown, Tex.). 8(2) 218-22 PMID: 19158498 |

Li H, Wang J, Mor G, Sklar J, A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells., 2008; Science (New York, N.Y.). 321(5894) 1357-61 PMID: 18772439 |

Li H, Ma X, Wang J, Koontz J, Nucci M, Sklar J, Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival., 2007; Proceedings of the National Academy of Sciences of the United States of America. 104(50) 20001-6 PMID: 18077430 | PMCID: PMC2148412

Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L, Lutterbaugh J, Rerko RM, Casey G, Issa JP, Willis J, Willson JK, Plass C, Markowitz SD, SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers., 2003; Proceedings of the National Academy of Sciences of the United States of America. 100(14) 8412-7 PMID: 12829793 | PMCID: PMC166243

Li H, Myeroff L, Kasturi L, Krumroy L, Schwartz S, Willson JK, Stanbridge E, Casey G, Markowitz S, Chromosomal autonomy of hMLH1 methylation in colon cancer., 2002; Oncogene. 21(9) 1443-9 PMID: 11857087 |