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Hui Li

Hui Li

Professor, Pathology

Primary Location
345 Crispell Drive
Carter Harrison Bldg(MR6), Room B524
Charlottesville, VA 22908
Primary Phone Number
434.982.6680
Fax Number
434.243.7244
Email
[email protected]
Website
http://lilab.medicine.virginia.edu

Bio & Overview

Targeted therapy: by serendipity, we identified a novel oncogene, and found that multiple cancers are addicted to its activity. This oncogene addiction is evidenced in glioblastoma, pediatric sarcoma, and others. About half of the lab members are working on figuring out the mechanisms of this oncogene, how is it activated, how does it work, and developing small molecule inhibitors to target it. Various animal models are also constructed to study its fundamental biology as well as testing the efficacy and safety of small molecule compounds. Chimeric RNA and system biology: 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. Immune therapy: The new process of RNA splicing offers a new repertoire for potential biomarkers and therapeutic targets. We found such chimeric RNA specifically expressed in various cancer types. A subset of them encode novel proteins or peptides. They represent ideal neo-antigens as cancer vaccine. Some are also membrane proteins which enable the CAR-T therapy or antibody conjugated drug development.

Academic Information

Department
Pathology
Academic Title
Associate Professor

Primary Education

  • BS, Chemical Physics, University of Science and Technology of China, China, 1998
  • PhD, Molecular Biology, Case Western Reserve University, 2003
  • Postdoc, Molecular Biology, Yale University, New Haven, CT, 2009

Other Appointments

  • Associate Professor, Biochemistry and Molecular Genetics
  • Public Health Sciences
  • Assistant Professor, MII
  • Assistant Professor, BMBG
  • Assistant Professor, MOMD

Other Affiliations

  • Cancer Center
  • Cancer Center
  • Member, Women's Oncology Program
  • Center for Public Health Genomics
  • MSTP
  • Associate Professor, BIMS

Research Interests

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

Research Disciplines

  • Biochemistry
  • Bioinformatics and Genomics
  • Biotechnology
  • Cancer Biology
  • Computational Biology
  • Development, Stem Cells & Regeneration
  • Epigenetics
  • Experimental Pathology
  • Genetics
  • Molecular Biology
  • Molecular Physiology and Biological Physics
  • Molecular and Cellular Physiology
  • Neuroscience
  • Structural Biology
  • Translational Science

Research Opportunities

  • Bioinformatics & Genomics
  • Cancer Biology
  • Cancer Immunology and Immunotherapy
  • Computational Biology
  • Experimental Pathology

PhD Programs

  • Biochemistry & Molecular Genetics
  • Experimental Pathology

Selected Publications

2024

Singh, S., Shi, X., Haddox, S., Elfman, J., Ahmad, S. B., Lynch, S., . . . Li, H. (2024). RTCpredictor: identification of read-through chimeric RNAs from RNA sequencing data. BRIEFINGS IN BIOINFORMATICS, 25(4). doi:10.1093/bib/bbae251

Elfman, J., Goins, L., Heller, T., Singh, S., Wang, Y. -H., & Li, H. (2024). Discovery of a polymorphic gene fusion via bottom-up chimeric RNA prediction. NUCLEIC ACIDS RESEARCH. doi:10.1093/nar/gkae258

Wang, Q., Cheng, B., Singh, S., Tao, Y., Xie, Z., Qin, F., . . . Huang, H. (2024). A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3. NPJ PRECISION ONCOLOGY, 8(1). doi:10.1038/s41698-024-00503-2

2023

Chen, C., Qin, F., Singh, S., Tang, Y., & Li, H. (2023). CTNNBIP1-CLSTN1 functions as a housekeeping chimeric RNA and regulates cell proliferation through SERPINE2. CELL DEATH DISCOVERY, 9(1). doi:10.1038/s41420-023-01668-8

Cornelison, R., Marrah, L., Fierti, A., Piczak, C., Glowczyk, M., Tajammal, A., . . . Li, H. (2023). The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(18). doi:10.3390/ijms241814196

Li, H., & Wang, Q. (2023). Chimeric RNAs and their implication in prostate cancer.. Cancer pathogenesis and therapy, 1(3), 216-219. doi:10.1016/j.cpt.2023.04.003

Dutta, A., Li, H., & Abounader, R. (2023). Cryptic lncRNA-encoded ORFs: A hidden source of regulatory proteins. JOURNAL OF CLINICAL INVESTIGATION, 133(5). doi:10.1172/JCI167271

2022

Lee, H. -Y., Jang, H. R., Li, H., Samuel, V. T., Dudek, K. D., Osipovich, A. B., . . . Shulmane, G. I. (2022). Deletion of Jazf 1 gene causes early growth retardation and insulin resistance in mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(49). doi:10.1073/pnas.2213628119

Elagib, K. E., Brock, A., Clementelli, C. M., Mosoyan, G., Delehanty, L. L., Sahu, R. K., . . . Goldfarb, A. N. (2022). Relieving DYRK1A repression of MKL1 confers an adult- like phenotype to human infantile megakaryocytes. JOURNAL OF CLINICAL INVESTIGATION, 132(19). doi:10.1172/JCI154839

Wang, Q., Chen, J., Singh, S., Xie, Z., Qin, F., Shi, X., . . . Huang, H. (2022). Profile of chimeric RNAs and TMPRSS2-ERG e2e4 isoform in neuroendocrine prostate cancer. CELL AND BIOSCIENCE, 12(1). doi:10.1186/s13578-022-00893-5

Xie, Z., Janczyk, P. L., Shi, X., Wang, Q., Singh, S., Cornelison, R., . . . Li, H. (2022). Rhabdomyosarcomas are oncogene addicted to the activation of AVIL. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(24). doi:10.1073/pnas.2118048119

Sun, Y., & Li, H. (2022). Chimeric RNAs Discovered by RNA Sequencing and Their Roles in Cancer and Rare Genetic Diseases. GENES, 13(5). doi:10.3390/genes13050741

2021

Cornelison, R., Marrah, L., Horter, D., Lynch, S., & Li, H. (2021). Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(24). doi:10.3390/ijms222413635

Wang, Q., Li, Z., Yang, J., Peng, S., Zhou, Q., Yao, K., . . . Huang, H. (2022). Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer. CANCER BIOLOGY & MEDICINE, 19(8), 1193-1210. doi:10.20892/j.issn.2095-3941.2020.0550

Singh, S., & Li, H. (2021). Comparative study of bioinformatic tools for the identification of chimeric RNAs from RNA Sequencing. RNA BIOLOGY, 18, 254-267. doi:10.1080/15476286.2021.1940047

Chen, C., Haddox, S., Tang, Y., Qin, F., & Li, H. (2021). Landscape of Chimeric RNAs in Non-Cancerous Cells. GENES, 12(4). doi:10.3390/genes12040466

2020

Xie, R., Chen, X., Chen, Z., Huang, M., Dong, W., Gu, P., . . . Lin, T. (2021). Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM (vol 449, pg 31, 2019). CANCER LETTERS, 500, 292-293. doi:10.1016/j.canlet.2020.12.027

Xie, Z., Janczyk, P. L., Zhang, Y., Liu, A., Shi, X., Singh, S., . . . Li, H. (2020). A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-17279-1

Elfman, J., Lam-Phong, P., & Li, H. (2020). The relationship between chimeric RNAs and gene fusions: Potential implications of reciprocity in cancer. JOURNAL OF GENETICS AND GENOMICS, 47(7), 341-348. doi:10.1016/j.jgg.2020.04.005

Wu, H., Singh, S., Xie, Z., Li, X., & Li, H. (2020). Landscape characterization of chimeric RNAs in colorectal cancer. CANCER LETTERS, 489, 56-65. doi:10.1016/j.canlet.2020.05.037

Shi, X., Singh, S., Lin, E., & Li, H. (2021). Chimeric RNAs in cancer. ADVANCES IN CLINICAL CHEMISTRY, VOL 100, 100, 1-35. doi:10.1016/bs.acc.2020.04.001

Li, K., Peng, S., Li, Z., Lai, Y., Wang, Q., Tao, Y., . . . Huang, H. (2020). Topoisomerase II-binding protein 1 promotes the progression of prostate cancer via ATR-CHK1 signaling pathway. AGING-US, 12(10), 9948-9958. doi:10.18632/aging.103260

Oostdyk, L. T., Wang, Z., Zang, C., Li, H., McConnell, M. J., & Paschal, B. M. (2020). An epilepsy-associated mutation in the nuclear import receptor KPNA7 reduces nuclear localization signal binding. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-61369-5

Singh, S., Qin, F., Kumar, S., Elfman, J., Lin, E., Lam-Phong, P., . . . Li, H. (2020). The landscape of chimeric RNAs in non-diseased tissues and cells. NUCLEIC ACIDS RESEARCH, 48(4), 1764-1778. doi:10.1093/nar/gkz1223

2019

Zhao, J., Tang, J., Elfman, J., & Li, H. (2020). RNase Protection Assay. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 109-116. doi:10.1007/978-1-4939-9904-0_8

Elfman, J., & Li, H. (2020). Detection and Measurement of Chimeric RNAs by RT-PCR. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 83-94. doi:10.1007/978-1-4939-9904-0_6

Singh, S., & Li, H. (2020). Prediction, Characterization, and In Silico Validation of Chimeric RNAs. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 3-12. doi:10.1007/978-1-4939-9904-0_1

Qin, F., Shi, X., & Li, H. (2020). Knockdown of Chimeric RNA by RNAi. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 143-154. doi:10.1007/978-1-4939-9904-0_11

Singh, S., & Li, H. (2020). Validation of Chimeric Fusion Peptides Using Proteomics Data. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 117-124. doi:10.1007/978-1-4939-9904-0_9

Wu, H., & Li, H. (2020). Overexpression of Chimeric RNA by Retroviral Transduction. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 155-166. doi:10.1007/978-1-4939-9904-0_12

Qin, F., Shi, X., & Li, H. (2020). Separation of Nuclear and Cytoplasmic Fractions for Chimeric RNA Characterization. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 167-175. doi:10.1007/978-1-4939-9904-0_13

Shi, X., Qin, F., & Li, H. (2020). Confirmation of Transcriptional Read-Through Events by RT-PCR. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 177-186. doi:10.1007/978-1-4939-9904-0_14

Zhu, D., & Li, H. (2020). Case Study: Landscape of Chimeric RNAs in Bladder Cancer. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 233-241. doi:10.1007/978-1-4939-9904-0_18

Tang, Y., Guan, F., & Li, H. (2020). Case Study: The Recurrent Fusion RNA DUS4L-BCAP29 in Noncancer Human Tissues and Cells. CHIMERIC RNA: METHODS AND PROTOCOLS, 2079, 243-258. doi:10.1007/978-1-4939-9904-0_19

Wu, H., Singh, S., Shi, X., Xie, Z., Lin, E., Li, X., & Li, H. (2020). Functional heritage: the evolution of chimeric RNA into a gene. RNA BIOLOGY, 17(1), 125-134. doi:10.1080/15476286.2019.1670038

Wu, H., Li, X., & Li, H. (2019). Gene fusions and chimeric RNAs, and their implications in cancer. GENES & DISEASES, 6(4), 385-390. doi:10.1016/j.gendis.2019.08.002

Balogh, P., Adelman, E. R., Pluvinage, J. V., Capaldo, B. J., Freeman, K. C., Singh, S., . . . Goldfarb, A. N. (2020). RUNX3 levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance. HAEMATOLOGICA, 105(4), 905-913. doi:10.3324/haematol.2018.208918

Zhu, D., Singh, S., Chen, X., Zheng, Z., Huan, J., Lin, T., & Li, H. (2019). The landscape of chimeric RNAs in bladder urothelial carcinoma (vol 110, pg 50, 2019). INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 111, 11. doi:10.1016/j.biocel.2019.03.011

Tang, Y., Ma, S., Wang, X., Xing, Q., Huang, T., Liu, H., . . . Guan, F. (2019). Identification of chimeric RNAs in human infant brains and their implications in neural differentiation. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 111, 19-26. doi:10.1016/j.biocel.2019.03.012

Zhu, D., Singh, S., Chen, X., Zheng, Z., Huang, J., Lin, T., & Li, H. (2019). The landscape of chimeric RNAs in bladder urothelial carcinoma. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 110, 50-58. doi:10.1016/j.biocel.2019.02.007

Xie, R., Chen, X., Chen, Z., Huang, M., Dong, W., Gu, P., . . . Lin, T. (2019). Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM. CANCER LETTERS, 449, 31-44. doi:10.1016/j.canlet.2019.01.041

Chen, Z., Chen, X., Xie, R., Huang, M., Dong, W., Han, J., . . . Lin, T. (2019). DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression. MOLECULAR THERAPY, 27(2), 326-341. doi:10.1016/j.ymthe.2018.12.015

Xie, Z., Tang, Y., Su, X., Cao, J., Zhang, Y., & Li, H. (2019). PAX3-FOXO1 escapes miR-495 regulation during muscle differentiation. RNA BIOLOGY, 16(1), 144-153. doi:10.1080/15476286.2018.1564464

2018

Parameswaran, S., Vizeacoumar, F. S., Bhanumathy, K. K., Qin, F., Islam, M. F., Toosi, B. M., . . . Vizeacoumar, F. J. (2019). Molecular characterization of an MLL1 fusion and its role in chromosomal instability. MOLECULAR ONCOLOGY, 13(2), 422-440. doi:10.1002/1878-0261.12423

Chwalenia, K., Qin, F., Singh, S., & Li, H. (2019). A cell-based splicing reporter system to identify regulators of cis-splicing between adjacent genes. NUCLEIC ACIDS RESEARCH, 47(4). doi:10.1093/nar/gky1288

Wu, P., Yang, S., Singh, S., Qin, F., Kumar, S., Wang, L., . . . Li, H. (2018). The Landscape and Implications of Chimeric RNAs in Cervical Cancer. EBIOMEDICINE, 37, 158-167. doi:10.1016/j.ebiom.2018.10.059

Chen, C., He, W., Huang, J., Wang, B., Li, H., Cai, Q., . . . Lin, T. (2018). LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment. NATURE COMMUNICATIONS, 9. doi:10.1038/s41467-018-06152-x

Elfman, J., & Li, H. (2018). Chimeric RNA in Cancer and Stem Cell Differentiation. STEM CELLS INTERNATIONAL, 2018. doi:10.1155/2018/3178789

2017

Huang, R., Kumar, S., & Li, H. (2017). Absence of Correlation between Chimeric RNA and Aging. GENES, 8(12). doi:10.3390/genes8120386

Chwalenia, K., Qin, F., Singh, S., Tangtrongstittikul, P., & Li, H. (2017). Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA. GENES, 8(11). doi:10.3390/genes8110338

Li, Z., Qin, F., & Li, H. (2018). Chimeric RNAs and their implications in cancer. CURRENT OPINION IN GENETICS & DEVELOPMENT, 48, 36-43. doi:10.1016/j.gde.2017.10.002

Qin, F., Zhang, Y., Liu, J., & Li, H. (2017). SLC45A3-ELK4 functions as a long non-coding chimeric RNA. CANCER LETTERS, 404, 53-61. doi:10.1016/j.canlet.2017.07.007

Chwalenia, K., Facemire, L., & Li, H. (2017). Chimeric RNAs in cancer and normal physiology. WILEY INTERDISCIPLINARY REVIEWS-RNA, 8(6). doi:10.1002/wrna.1427

Tang, Y., Qin, F., Liu, A., & Li, H. (2017). Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells. ONCOTARGET, 8(19), 31415-31423. doi:10.18632/oncotarget.16329

Kumar, S., & Li, H. (2017). In Silico Design of Anticancer Peptides. PROTEOMICS FOR DRUG DISCOVERY: METHODS AND PROTOCOLS, 1647, 245-254. doi:10.1007/978-1-4939-7201-2_17

Xie, Z., Jia, Y., & Li, H. (2017). Studying Protein-Protein Interactions by Biotin AP-Tagged Pulldown and LTQ-Orbitrap Mass Spectrometry. PROTEOMICS FOR DRUG DISCOVERY: METHODS AND PROTOCOLS, 1647, 129-138. doi:10.1007/978-1-4939-7201-2_8

2016

Xie, Z., & Li, H. (2017). Fusion RNA profiling provides hints on cell of origin of mysterious tumor. MOLECULAR & CELLULAR ONCOLOGY, 4(1). doi:10.1080/23723556.2016.1263714

Xie, Z., Babiceanu, M., Kumar, S., Jia, Y., Qin, F., Barr, F. G., & Li, H. (2016). Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(46), 13126-13131. doi:10.1073/pnas.1612734113

Jia, Y., Xie, Z., & Li, H. (2016). Intergenically Spliced Chimeric RNAs in Cancer. TRENDS IN CANCER, 2(9), 475-484. doi:10.1016/j.trecan.2016.07.006

Kumar, S., Razzaq, S. K., Vo, A. D., Gautam, M., & Li, H. (2016). Identifying fusion transcripts using next generation sequencing. WILEY INTERDISCIPLINARY REVIEWS-RNA, 7(6), 811-823. doi:10.1002/wrna.1382

Qin, F., Song, Z., Chang, M., Song, Y., Frierson, H., & Li, H. (2016). Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer. CANCER LETTERS, 380(1), 39-46. doi:10.1016/j.canlet.2016.06.013

Kumar, S., Vo, A. D., Qin, F., & Li, H. (2016). Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data. SCIENTIFIC REPORTS, 6. doi:10.1038/srep21597

Babiceanu, M., Qin, F., Xie, Z., Jia, Y., Lopez, K., Janus, N., . . . Li, H. (2016). Recurrent chimeric fusion RNAs in non-cancer tissues and cells. NUCLEIC ACIDS RESEARCH, 44(6), 2859-2872. doi:10.1093/nar/gkw032

Qin, F., Song, Y., Zhang, Y., Facemire, L., Frierson, H., & Li, H. (2016). Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA. PLOS ONE, 11(3). doi:10.1371/journal.pone.0150382

2015

Pires, E. S., D'Souza, R. S., Needham, M. A., Herr, A. K., Jazaeri, A. A., Li, H., . . . Herr, J. C. (2015). Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors. ONCOTARGET, 6(30), 30194-30211. doi:10.18632/oncotarget.4734

Qin, F., Song, Z., Babiceanu, M., Song, Y., Facemire, L., Singh, R., . . . Li, H. (2015). Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells. PLOS GENETICS, 11(2). doi:10.1371/journal.pgen.1005001

2014

Jividen, K., & Li, H. (2014). Chimeric RNAs Generated by Intergenic Splicing in Normal and Cancer Cells. GENES CHROMOSOMES & CANCER, 53(12), 963-971. doi:10.1002/gcc.22207

Jividen, K., Movassagh, M. J., Jazaeri, A., & Li, H. (2014). Two Methods for Establishing Primary Human Endometrial Stromal Cells from Hysterectomy Specimens. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (87). doi:10.3791/51513

2013

Yuan, H., Qin, F., Movassagh, M., Park, H., Golden, W., Xie, Z., . . . Li, H. (2013). A Chimeric RNA Characteristic of Rhabdomyosarcoma in Normal Myogenesis Process. CANCER DISCOVERY, 3(12), 1394-1403. doi:10.1158/2159-8290.CD-13-0186

2012

Zhang, Y., Gong, M., Yuan, H., Park, H. G., Frierson, H. F., & Li, H. (2012). Chimeric Transcript Generated by cis-Splicing of Adjacent Genes Regulates Prostate Cancer Cell Proliferation. CANCER DISCOVERY, 2(7), 598-607. doi:10.1158/2159-8290.CD-12-0042

2011

Jazaeri, A. A., Bryant, J. L., Park, H., Li, H., Dahiya, N., Stoler, M. H., . . . Dutta, A. (2011). Molecular Requirements for Transformation of Fallopian Tube Epithelial Cells into Serous Carcinoma. NEOPLASIA, 13(10), 899-U44. doi:10.1593/neo.11138