Molecular and Cellular Biochemistry

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Pic Dr. Liu

Chunming Liu
Associate Professor
Postdoctoral Fellowship, Harvard Medical School
Ph.D.Purdue University, 1997
B.S., Nankai University

Office: 859-323-4558
Email: chunming.liu@uky.edu

Overview ▪ Recent Publications ▪ PubMed

Graduate Students and Postdoc Positions are available

Overview
Recent Publications ▪ PubMed

The Wnt/ß-catenin signaling pathway plays important roles in early development, stem cell renewal, and tumorigenesis. In addition, Wnt signaling is crucial in the organization and maintenance of the human intestinal epithelium. In this pathway, many different components work together to transduce an external signal into changes in gene expression within the target cell. Upon binding its receptor, the Wnt ligand ultimately results in the stabilization of cytoplasmic ß-catenin, which is then free to enter the nucleus and activate transcription through its interaction with the TCF/LEF family of transcription factors.

ß-catenin/KLF4 crosstalk regulates tumorigenesis and differentiation

Somatic mutations that result in deregulated Wnt signaling are an early event in the development of colorectal cancer, which is the second leading cause of cancer death in the United States. About 80% of colorectal cancers have APC (adenomatous polyposis coli) mutation, and about 15% have β-catenin mutation. We have identified novel molecules in the Wnt pathways, and have provided insights into how mutations cause ß-catenin accumulation that leads to cancer.

We are also interested in the crosstalk between Wnt signaling and other signaling pathways. We have identified KLF4 as a novel inhibitor of β-catenin. KLF4 is a tumor suppressor and a key factor for stem cell re-programming. We found that KLF4 controls transcription by regulating chromatin-remodeling. We are currently investigating the molecular mechanisms of KLF4 in cancers and in iPS cells (induced pluripotent stem cells).

We are collaborating with clinicians in the Markey Cancer Center to study Wnt/ß-catenin signaling in human cancers, especially GI cancers. We are collaborating with chemists at UK and Biotech companies to develop β-catenin inhibitors. Our long-term goal is to investigate the molecular mechanisms of human cancers, including cancer stem cells, and to use our knowledge of cell signaling to develop novel therapeutics and diagnostics for GI cancers.

Overview ▪ PubMed

Selected Publications

Zhang W, Yang J, Liu Y, Chen X, Yu T, Jia J and Liu C. PR55a, a regulatory subunit of PP2A, specifically regulates PP2A-mediated β-catenin dephosphorylation. J Biol Chem, Epub ahead of print, 2009.

Song S, Mazurek N, Liu C, Liu K, Hung MC and Bresalier RS. Galectin-3 Mediates Nuclear β-catenin Accumulation and Wnt Signaling in Human Colon Cancer Cells by Regulation of GSK-3b Activity. Cancer Research 69: 1343-9, 2009.

Zheng H, Pritchard DM, Yang X, Bennett E, Liu G, Liu C and Ai W. KLF4 gene expression is inhibited by the Notch signaling pathway that controls goblet cell differentiation in mouse GI tract. Am J Physiol Gastrointest Liver Physiol 296: G490-82008, 2009.

Evans PM and Liu C. Role of Krüppel-like factor 4 in normal homeostasis, cancer, and stem cells. Acta Biochim Biophys Sin 40: 554-564, 2008 (review).

Chen X, Yang J, Evans PM and Liu C. Wnt signaling: the good and the bad. Acta Biochim Biophys Sin 40:577-94, 2008 (review).

Evans PM, Zhang W, Chen X, Yang J, Bhakat K and Liu C. Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation. J Biol Chem 282:33994-4002, 2007.

Zhang B, Luo S, Dong XP, Zhang X, Liu C, Luo Z, Xiong WC and Mei L. β-catenin regulates AChR clustering in muscle cells through interaction with rapsyn. J Neurosci 27:3968-3973, 2007.

Yang J, Zhang W, Evans PM, Chen X, He X and Liu C. APC differentially regulates β-catenin phosphorylation and ubiquitination in colon cancer cells. J Biol Chem 281:17751-17757, 2006.

Zhang W, Chen X, Kato Y, Evans PM, Yuan S, Yang J, Rychahou PG, Yang VW, He X, Evers BM and Liu C. Novel crosstalk of Krüppel-like factor 4 and β-catenin regulates normal intestinal homeostasis and tumor repression. Mol Cell Biol 26:2055-2064, 2006.

Evans PM, Liu C. SiteFind: A software tool for introducing a restriction site as a marker for successful site-directed mutagenesis. BMC Mol Biol 6:22, 2005.

Shao J, Jung C, Liu C and Sheng H. Prostaglandin E2 stimulates the β-catenin/TCF-dependent transcription in colon cancer. J Biol Chem 280:26565-26572, 2005.

Wu G, Liu C, and He X. Ozz: A new name on the long list of β-catenin's nemeses. Mol Cell 13: 451-453, 2004 (review).

Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, and He X. A mechanism for Wnt co-receptor activation. Mol Cell 13:149-156, 2004.

Liu C, Li Y, Semenov M, Han C, Baeg G, Tan Y, Zhang Z, Lin X, He X. Control of β-catenin phosphorylaton/degradation by a dual-kinase mechanism. Cell 108:837-847, 2002.

Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X. LDL-receptor-related proteins in Wnt signal transduction. Nature 407: 530-535, 2000.

Liu C, Kato Y, Zhang Z, Do VM, Yankner BA and He X. β-Trcp couples β-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad of Sci USA 96:6273-6278, 1999.