Hui Li, Ph.D.

Professor of Pathology
lilab.medicine.virginia.edu

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:

Targeted therapy: by serendipity, we identified a novel oncogene, and found that multiple cancers are addicted to its activity. This oncogene addiction is evidenced in glioblastoma, pediatric sarcoma, and others. About half of the lab members are working on figuring out the mechanisms of this oncogene, how is it activated, how does it work, and developing small molecule inhibitors to target it. Various animal models are also constructed to study its fundamental biology as well as testing the efficacy and safety of small molecule compounds.

Chimeric RNA and system biology: 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.

Immune therapy: The new process of RNA splicing offers a new repertoire for potential biomarkers and therapeutic targets. We found such chimeric RNA specifically expressed in various cancer types. A subset of them encode novel proteins or peptides. They represent ideal neo-antigens as cancer vaccine. Some are also membrane proteins which enable the CAR-T therapy or antibody conjugated drug development.

Selected Publications:

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.