- PhD, Case Western Reserve University
- Postdoc, Yale University, New Haven, CT
- BS, University of Science and Technology of China, China
- Associate Professor, Pathology
Gene regulation in cancer, development and reproductive systems; Epigenetic modification.
Our research focuses on chimeric RNA in cancer and normal cells. Gene fusion is a common feature of cancer. The fusion products were believed to be unique to cancer cells until we recently demonstrated that abundant levels of fusion products can also be present in normal cells. In these normal cells, the fusion products are made by a post-transcriptional process called "trans-splicing" and may serve important functions. Our long-term hypotheses are that such trans-splicings are not rare events and that they play critical roles in normal physiology. In addition, mis-regulated trans-splicing machinery could generate highly abundant fusion products, which would promote oncogenesis the same way as the products made by traditional chromosomal rearrangements. To discover more RNA trans-splicing events, we propose two approaches, a candidate gene approach and a genome-wide approach. The candidate gene approach would focus on the known gene fusions associated with chromosomal translocations in various tumors. We predict that at least some of the fusion products can also be detected in the normal corresponding cells under certain conditions. The key is "when" and "where" to look for such events. We are applying a stem cell differentiation approach to uncover these previously believed to be "cancer specific" fusions. For the genome-wide approach, we are using paired-end RNA-seq and several software tools to uncover novel fusion events and to document the whole transcriptome trans-splicing events in the cells of interest. Gain of function and loss of function approaches will be used to study the effect of the trans-spliced chimeric products on cancer development.
Another way to generate chimeric RNA between neighboring genes transcribing in the same direction is what we called "cis-splicing of adjacent genes" (cis-SAGe). It happens as if the gene boundaries do not exist. We are again using RNA-seq and bioinformatics tools to find more cis-SAGe events.
Some of the fusions we found promise to be ideal biomarkers and/or therapeutic targets.
- 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