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Chen Guan MD PhD

Guan-Chen-PhD

Guan Chen, MD, PhD

Professor

Contact Information

Biography

General Interests

Cancer Research

Education

1982, Bengbu Medical College, MD
1985, Sun Yat-Sen University, MS
1990, University of Heidelberg, Germany, PhD

Research Interests

Dr. Chen's Faculty Collaboration Database

Ras is the most established oncogene in human cancer, with its mutation (K-Ras) occurring in about 50% human colon cancer and its hyperexpression (H-Ras) in more than 50% of human breast cancer. Ras oncogene activity, however, is determined by downstream effectors and elucidation of this regulation is essential to understand why not all Ras mutations can lead to human malignancies. MAPKs (mitogen-activated protein kinases), including ERK, JNK, and p38, signal downstream of Ras by converting extracellular and Ras signals into specific cellular response through a group of transcription factors. Our previous work established that Ras-induced p38 alpha phosphorylation/activation inhibits the oncogene activity by negative feedback. Results from our recent studies further showed that p38 gamma, a p38 family protein, is induced by Ras and in turn required for Ras transformation in rat intestinal epithelial cells and for Ras-invasive activity in human breast cancer. These results together indicate that signaling integrations among p38 family members determine Ras oncogene activity in a given tissues and p38 proteins regulate Ras activity by isoform-dependent mechanisms. Currently, we are investigating mechanisms by which Ras induces p38 gamma expression and by which p38gamma is required for Ras-induced transformation / invasion.

Nuclear receptors are group of transcription factors that play an important role in reproduction, homeostasis, and cancer development through regulating gene expression in response to their ligand. Our second research interest is to study signal cross-talks between Ras/MAPK pathways and nuclear receptors. Studies from our lab have established a c-Jun/AP-1 dependent trans-activation for stress-induced vitamin D receptor (VDR) expression and an anti-apoptotic activity of VDR by a K-ras-dependent mechanism. Our results further showed that another nuclear receptor ER (estrogen receptor) inhibits stress MAPK-mediated cell death independent of its transcriptional activity by converting pro-apoptotic c-Jun activity into a c-Jun-dependent AP1 transcription. These results together suggest that nuclear receptors may cooperate with Ras/MAPKs to regulate stress-response independent of their transcription activity. We are currently investigating whether regulation of nuclear receptors represents a novel strategy for human cancer treatment.

Publications