Dawei Xu

Telomerase, a ribonucleoprotein enzyme required for maintenance of telomere length, is implicated in aging and cancer. It is silent in the majority of human normal cells due to a tight repression of its catalytic component hTERT (telomerase reverse transcriptase) gene. Activation of telomerase by induction of hTERT expression has been shown to be a prerequisite step in cellular immortalization and malignant transformation. I study the mechanism(s) that control the regulated switch between repression and activation of the hTERT gene or telomerase in normal and malignant human cells, with special interest in the role of epigenetic factors. The obtained results are believed to contribute to rational development of the anti-aging/cancer strategy by manipulating telomerase expression.

Selected publications

Activation of telomerase by human cytomegalovirus J Natl Cancer Inst 2009;101:488-497.
FoxM1 is up-regulated in gastric cancer and its inhibition leads to cellular senescence, partially dependent on p27 kip1 J Pathol 2009;218:419-427
The telomerase reverse transcriptase (hTERT) gene is a direct target of the histone methyltransferase SMYD3 Cancer Res 2007; 67:2626-2631
Mitogen-activated protein kinase cascade-mediated histone H3 phosphorylation is critical for telomerase reverse transcriptase expression/telomerase activation induced by proliferation Mol Cell Biol 2006; 26:230-237
Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in cri-du-chat syndrome Am J Hum Genet 2003; 72:940-948
Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells Proc Nat Acad Sci USA 2001; 98:3826-3831
Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells Oncogene 2000;19:5123-5133

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