Hui Li

Education

  • PhD, Case Western Reserve University
  • Postdoc, Yale University, New Haven, CT
  • BS, University of Science and Technology of China, China

Primary Appointment

  • Associate Professor, Pathology

Contact

Research Interest(s)

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

  • Chwalenia K, Facemire L, Li H. Chimeric RNAs in cancer and normal physiology. Wiley interdisciplinary reviews. RNA. 2017. PMID: 28589684
  • Jia Y, Xie Z, Li H. Intergenically Spliced Chimeric RNAs in Cancer. Trends in cancer. 2017;2(9): 475-484. PMID: 28210711 | PMCID: PMC5305119
  • Qin F, Zhang Y, Liu J, Li H. SLC45A3-ELK4 functions as a long non-coding chimeric RNA. Cancer letters. 2017;404 53-61. PMID: 28716526
  • Tang Y, Qin F, Liu A, Li H. Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells. Oncotarget. 2017;8(19): 31415-31423. PMID: 28415823 | PMCID: PMC5458218
  • Xie Z, Li H. Fusion RNA profiling provides hints on cell of origin of mysterious tumor. Molecular & cellular oncology. 2017;4(1): e1263714. PMID: 28197537 | PMCID: PMC5287003
  • Babiceanu M, Qin F, Xie Z, Jia Y, Lopez K, Janus N, Facemire L, Kumar S, Pang Y, Qi Y, Lazar I, Li H. Recurrent chimeric fusion RNAs in non-cancer tissues and cells. Nucleic acids research. 2016;44(6): 2859-72. PMID: 26837576 | PMCID: PMC4824105
  • Kumar S, Razzaq S, Vo A, Gautam M, Li H. Identifying fusion transcripts using next generation sequencing. Wiley interdisciplinary reviews. RNA. 2016;7(6): 811-823. PMID: 27485475 | PMCID: PMC5065767
  • Kumar S, Vo A, Qin F, Li H. Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data. Scientific reports. 2016;6 21597. PMID: 26862001 | PMCID: PMC4748267
  • Qin F, Song Y, Zhang Y, Facemire L, Frierson H, Li H. Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA. PloS one. 2016;11(3): e0150382. PMID: 26938874 | PMCID: PMC4777538
  • Qin F, Song Z, Chang M, Song Y, Frierson H, Li H. Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer. Cancer letters. 2016;380(1): 39-46. PMID: 27322736
  • Xie Z, Babiceanu M, Kumar S, Jia Y, Qin F, Barr F, Li H. Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(46): 13126-13131. PMID: 27799565 | PMCID: PMC5135356
  • Pires E, D'Souza R, Needham M, Herr A, Jazaeri A, Li H, Stoler M, Anderson-Knapp K, Thomas T, Mandal A, Gougeon A, Flickinger C, Bruns D, Pollok B, Herr J. Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors. Oncotarget. 2015;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. PLoS genetics. 2015;11(2): e1005001. PMID: 25658338 | PMCID: PMC4450057
  • Jividen K, Li H. Chimeric RNAs generated by intergenic splicing in normal and cancer cells. Genes, chromosomes & cancer. 2014. 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. Cancer discovery. 2013;3(12): 1394-403. PMID: 24089019
  • Zhang Y, Gong M, Yuan H, Park H, Frierson H, Li H. Chimeric Transcript Generated by cis-Splicing of Adjacent Genes Regulates Prostate Cancer Cell Proliferation. Cancer discovery. 2012;2(7): 598-607. PMID: 22719019
  • Jazaeri A, Bryant J, Park H, Li H, Dahiya N, Stoler M, Ferriss J, Dutta A. Molecular requirements for transformation of fallopian tube epithelial cells into serous carcinoma. Neoplasia (New York, N.Y.). 2011;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. Cell cycle (Georgetown, Tex.). 2009;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. Science (New York, N.Y.). 2008;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. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(50): 20001-6. PMID: 18077430 | PMCID: PMC2148412
  • Li H, Myeroff L, Smiraglia D, Romero M, Pretlow T, Kasturi L, Lutterbaugh J, Rerko R, Casey G, Issa J, Willis J, Willson J, Plass C, Markowitz S. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(14): 8412-7. PMID: 12829793 | PMCID: PMC166243
  • Li H, Myeroff L, Kasturi L, Krumroy L, Schwartz S, Willson J, Stanbridge E, Casey G, Markowitz S. Chromosomal autonomy of hMLH1 methylation in colon cancer. Oncogene. 2002;21(9): 1443-9. PMID: 11857087