Hui Li, Ph.D.
Associate Professor of Pathology
Education and Training:
1998, B.S. Chemical Physics, University of Science and Technology of China, China
2003, Ph.D. Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH
2003-2006, Postdoctoral Associate, Pathology, Yale University, New Haven, CT
2006-2009 Associate Research Scientist, Pathology, Yale University, New Haven, CT
Gene fusion is a common feature of cancer. The fusion products were believed to be unique to cancer cells until recently we demonstrated that abundant level 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” to serve important functions. Our long-term hypotheses are that such trans-splicings are more than rare events and 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 at certain conditions. The key is “when” and “where” to look for such events.
For the genome-wide approach, we propose a modified “mate-pair” combined with “paired-end” deep sequencing approach to document the whole transcriptome trans-splicing events in the cells of interest. To validate the candidates of trans-splicing, we are developing an intra-cellular based trans-splicing assay with high throughput potential. Our preliminary studies support the second part of the hypothesis that at least some fusions are the mis-regulated products of trans-splicing. Gain of function and loss of function approaches will be used to study the effect of the trans-spliced chimeric products on cancer development. Our proposed trans-splicing study will enhance our knowledge of the genetic information flow, suggest a novel oncogenic pathway, and provide additional links between cancer and its normal origin cells. In addition, the proposed study of trans-splicing will have both immediate and long-term clinical implications.
- 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 Genet 2015, 11:e1005001.http://www.ncbi.nlm.nih.gov/pubmed/25658338. DOI: 10.1371/journal.pgen.1005001.
- Jividen K, Li H: Chimeric RNAs generated by intergenic splicing in normal and cancer cells. Genes Chromosomes Cancer 2014, 53:963-971. http://www.ncbi.nlm.nih.gov/pubmed/25131334. DOI: 10.1002/gcc.22207.
- Jividen K, Movassagh MJ, Jazaeri A, Li H: Two methods for establishing primary human endometrial stromal cells from hysterectomy specimens. J Vis Exp 2014, http://www.ncbi.nlm.nih.gov/pubmed/24894444. DOI: 10.3791/51513.
- 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 Discov 2013, 3:1394-1403.http://www.ncbi.nlm.nih.gov/pubmed/24089019. DOI: 10.1158/2159-8290.CD-13-0186.
- 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. Cancer Discov 2012, 2:598-607.http://www.ncbi.nlm.nih.gov/pubmed/22719019. DOI: 10.1158/2159-8290.CD-12-0042.
- 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. Neoplasia 2011, 13:899-911.http://www.ncbi.nlm.nih.gov/pubmed/22028616.
- Li H, Wang J, Ma X, Sklar J: Gene fusions and RNA trans-splicing in normal and neoplastic human cells. Cell Cycle 2009, 8:218-222. http://www.ncbi.nlm.nih.gov/pubmed/19158498.
- Li H, Wang J, Mor G, Sklar J: A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells. Science 2008, 321:1357-1361. http://www.ncbi.nlm.nih.gov/pubmed/18772439. DOI: 10.1126/science.1156725.
- 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. Proc Natl Acad Sci U S A 2007, 104:20001-20006.http://www.ncbi.nlm.nih.gov/pubmed/18077430. DOI: 10.1073/pnas.0709986104.
- 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. Proc Natl Acad Sci U S A 2003, 100:8412-8417.http://www.ncbi.nlm.nih.gov/pubmed/12829793. DOI: 10.1073/pnas.1430846100.
- 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. Oncogene 2002, 21:1443-1449.http://www.ncbi.nlm.nih.gov/pubmed/11857087. DOI: 10.1038/sj.onc.1205247.
Timeline for Dr. Li’s Lab:
7/2009 Dr. Li started the lab.
7/2009 Hong Park joined the lab and assisted in setting it up.
9/2009 Anna Lee joined the lab as an undergraduate volunteer.
9/2009 Dr. Gong Mei joined the lab as a Research Associate.
10/2009 Dr. Huiling Yuan joined the lab as a Research Associate.
3/2010 Dr. Li was awarded American Cancer Society IRG.
5/2010 Dr. Li was awarded Funds for Excellence in Science and Technology.
5/2010 Merritt Tuttle joined the lab as an undergraduate volunteer.
5/2010 Jongoh Lim joined the lab as a summer undergraduate volunteer.
9/2010 Marina Piper joined the lab as an undergraduate volunteer.
10/2010 Dr. Li was awarded V Scholarship.
12/2010 Dr. Yanmei Zhang joined the lab as a Research Associate.
01/2011 Callie Horn joined the lab as an undergraduate volunteer.
01/2011 Salma Nabi joined the lab as an undergraduate volunteer.
04/2011 Dr. Li was awarded Stand Up To Cancer Innovative Research Grant.