Hui Li, Ph.D.
Assistant 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
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
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,
Jividen K, Movassagh MJ, Jazaeri A, Li
: Two methods for establishing primary human endometrial
stromal cells from hysterectomy specimens. J Vis Exp 2014, http://www.ncbi.nlm.nih.gov/pubmed/24894444
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
Zhang Y, Gong M, Yuan H, Park HG, Frierson HF,
: 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
Jazaeri AA, Bryant JL, Park H, Li
, 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
, 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
, 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
, 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
Timeline for Dr. Li's Lab:
Li started the lab.
Park joined the lab and assisted in setting it up.
Lee joined the lab as an undergraduate volunteer.
Gong Mei joined the lab as a Research Associate.
Dr. Huiling Yuan joined the lab as a Research Associate.
Li was awarded American Cancer Society IRG.
Li was awarded Funds for Excellence in Science and Technology.
Merritt Tuttle joined the lab as an undergraduate volunteer.
Jongoh Lim joined the lab as a summer undergraduate volunteer.
Marina Piper joined the lab as an undergraduate volunteer.
Dr. Li was awarded V Scholarship.
Dr. Yanmei Zhang joined the lab as a Research Associate.
Callie Horn joined the lab as an undergraduate volunteer.
Salma Nabi joined the lab as an undergraduate volunteer.
Dr. Li was awarded Stand Up To Cancer Innovative Research Grant.