YONGQING LIU, B.S., M.S., Ph.D.
Department of Ophthalmology and Visual Sciences
Kentucky Lions Eye Center
301 E. Muhammad Ali Boulevard, Louisville KY 40202
Telephone: 502-852-8669 Fax: 502-852-0691
Wageningen University, Wageningen, the Netherlands – 1996
Molecular Biology - The Samuel Roberts Noble Foundation, Ardmore, OK - 1998-2000; Functional and Comparative Genomics – Oak Ridge National Laboratory, Oak Ridge, TN - 2001- 2003
My research interest branches into two related areas: 1) converting differentiated mammalian cells into stem-like cells through sphere formation in vitro, and re-directing them to specific differentiation for tissue regeneration in vivo; 2) exploring possible roles of the zinc finger E-box binding transcription factor Zeb1 in induced pluripotent stem cell (iPSC) and in solid tumor initiation and progression.
Tissue damages or functional disorders due to trauma, aging, and inheritable diseases like retinitis pigmentosa (RP), and age-related macular degeneration (AMD), are difficult to treat. More and more hope now relies on advances in regenerative medicine in which stem cell application is part of the solution. Recently, we have successfully converted differentiated somatic cells into stem-like cells by self-promoting expression of endogenous stem cell factors through sphere formation in vitro. As with iPSC, we are hoping that the sphere-induced pluripotent stem (SiPS) cells will facilitate patient-specific cell therapy in the clinic.
It is well-known that epithelial-mesenchymal transition (EMT) facilitates a metastatic phenotype in cancers; over-expression of EMT factors including Zeb1 is a hall marker in carcinomas. Mutation of Rb1 gene is a single causal factor for retinoblastoma (RB) in the human eye, which also up-regulates Zeb1 expression in cells. We have identified Zeb1 as an important factor together with Rb1 in regulation of cell cycle activities, thus essential for tumor initiation and progression, as well as stem cell maintenance and reactivation. To further understand how Zeb1 regulates tumor or stem cell behavior in vitro, we are using Zeb1 mutant transgenic mouse embryonic fibroblast (MEF) cells and its down- or up-regulation lentivirus to reveal possible molecular mechanism(s) in reprogramming somatic differentiated cells to stem-like cells.
PUBLICATIONS: (selected publications)
- Liu Y, Xin Y, Ye F, Wang W, Lu Q, Kaplan HJ, Dean DC. Taz-Tead1 Links Cell-Cell Contact to Zeb1 Expression, Proliferation and Dedifferentiation in Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 51:3372-8, 2010. PMID: 20207963
- Liu Y, Dean DC. Tumor initiation via loss of cell contact inhibition versus Ras mutation: Do all roads lead to EMT? Cell Cycle 9:897-900, 2010. PMID: 20160473
- El-Naggar S, Liu Y, Dean DC. Mutation of the Rb1 pathway leads to overexpression of mTor, constitutive phosphorylation of Akt on serine 473, resistance to anoikis, and a block in c-Raf activation. Mol Cell Biol 29:5710-7, 2009. PMID: 19703998
- Liu Y, Ye F, Li Q, Tamiya S, Darling D, Kaplan HJ, Dean DC. Zeb1 Represses Mitf and Regulates Pigment Synthesis, Cell Proliferation and Epithelial Morphology. 2009. Invest Ophthalmol Vis Sci. 50:5080-8, 2009. PMID: 19515996
- Liu Y, Gao L, Zuba-Surma EK, Peng X, Kucia M, Ratajczak MZ, Wang W, Enzman V, Kaplan HJ, Dean DC. Mouse Neonatal Ocular Multipotential Stem-like Cells. Exp Hematol. 37(9):1096-107, 2009. PMID: 19539690
- Montoya-Durango DE, Liu Y, Teneng I, Kalbfleisch T, Lacy ME, Steffen MC, Ramos KS. Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins. Mutat. Res. Fund. Mol. M. 665: 20-8, 2009. PMID: 19427507
- Liu Y, Clem B, Zuba-Surma EK, El-Naggar S, Telang S, Jenson AB, Wang Y, Shao H, Ratajczak MZ, Chesney J, Dean DC. Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype. Cell Stem Cell. 4:336-47, 2009. PMID: 19341623
- Liu Y, Wang E. Transcriptional analysis of normal human fibroblast responses to microgravity stress. Genomics Proteomics Bioinformatics. 6:29-41, 2008. PMID: 18558383
- Liu Y, Peng X, Tan J, Darling DS, Kaplan HJ, Dean DC. Zeb1 mutant mice as a model of posterior corneal dystrophy. Invest Ophthalmol Vis Sci. 49:1843-9, 2008. PMID: 18436818
- Liu Y, El-Naggar S, Clem B, Chesney J, Dean DC. The Rb/E2F pathway and Ras activation regulate RecQ helicase gene expression. Biochem J. 412:299-306, 2008. PMID: 18215118
- Liu Y, El-Naggar S, Darling DS, Higashi Y, Dean DC. Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development. 135:579-88, 2008. PMID: 18192284
- Liu Y, Costantino ME, Montoya-Durango D, Higashi Y, Darling DS, Dean DC. The zinc finger transcription factor ZFHX1A is linked to cell proliferation by Rb-E2F1. Biochem J. 408:79-85, 2007. PMID: 17655524
- Liu Y, Gao W, Wu L, Liu X, Yan T, Fields MW, Thompson DK Zhou JZ. Transcriptome analysis of Shewanella oneidensis MR-1 in response to elevated salt conditions. J Bacteriol. 187: 2501-2507, 2005. PMID: 15774893
- Liu Y, Zhou J, Omelchenko M, Beliaev A, Venkateswaran A, Stair J, Wu L, Thompson D, Xu D, Zhai M, Gaidamakova EK, Rogozin IB, Makarova KS, Koonin EV, Daly MJ. Transcriptome dynamics of Deinococcus radiodurans recovering from ionizing radiation. Proc. Natl. Acad. Sci. USA 100: 4191-4196, 2003. PMID: 12651953
- Liu Y, Dammann C, Bhattacharyya MK. The matrix metalloproteinase gene GmMMP2 is activated in response to pathogenic infections in soybean. Plant Physiology 127: 1788-1797, 2001. PMID: 11743122