Hui Li, Ph.D.
Assistant Professor
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
Research:
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.
Selected Publications:
- Hui Li*, Jinglan Wang, Xianyong Ma and Jeffrey
Sklar (2009) Gene fusions and RNA Trans-splicing in Normal and
Neoplastic Human Cells. Cell Cycle 2009
January 8:2, 1-5(* corresponding author)
- Hui Li, Jinglan Wang, Gil Mor and Jeffrey Sklar
(2008) A Neoplastic Gene Fusion Mimics Trans-splicing of RNAs in Normal
Cells. Science 2008 September 5;
321,1357-1361.
- Hui Li, XianYong Ma, Jinglan Wang, Jason Koontz,
Marisa Nucci and Jeffrey Sklar (2007) Effects of rearrangement and
allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival.
Proc Natl Acad Sci U S A. 2007 December 11;
104(50): 20001-20006.
- Hui Li, Lois Myeroff, Dominic Smiraglia, Michael
F. Romero, Theresa P. Pretlow, Lakshmi Kasturi, Jim Lutterbaugh, Ronald
M. Rerko, Graham Casey, Jean-Pierre Issa, Joseph Willis, James K.V.
Willson, Christoph Plass and Sanford Markowitz (2003) SLC5A8: A Novel
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 Jul 8; 100(14): 8412-7.
- Hui Li, Lois Myeroff, Lakshmi Kasturi, Lisa
Krumroy, Stuart Schwartz, James KV Willson, Eric Stanbridge, Graham
Casey and Sanford Markowitz (2002) Chromosomal autonomy of hMLH1
methylation in colon cancer. Oncogene 21,
1443-1449.
- Hui Li and Qing-xiang Guo. (1998) Recent Progress
in Studies on the Application of Cationic Liposome to Gene Therapy.
Ziran Zazhi (Chinese Nature) 20(5):
275-8.
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.
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