Medical College of Wisconsin
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Guan Chen, MD, PhD

Guan Chen, PhD

Guan Chen, MD, PhD

Professor

Contact Information

General Interests

Cancer Research

Education

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

Research Experience

  • p38gamma MAPK, Cancer Signaling, Ras Oncogenesis, Nuclear Receptors, Targeted Cancer Therapy

Research Interests

Cancer remains a life-threatening disease and there is an urgent need to identify novel molecular targets for therapeutic intervention. Our lab focuses on investigating oncogenic activity of p38gamma in colon, breast and pancreatic cancers. In colon cancer, p38gamma is required for K-Ras induced transformation and for K-Ras-dependent malignant growth through mechanisms involving collaboration with its phosphatase PTPH1, stimulating c-Jun/AP-1-dependent MMP9 transcription, and/or phosphorylating and activating Hsp90. p38gamma activation also causes increased EGFR transcription via -c-Jun and decreased EGFR phosphorylation via PTPH1, resulting in accumulation of non-phosphorylated EGFR and resistance to tyrosine kinase inhibitors. In breast cancer, p38gamma-overexpression alone induces malignant transformation in human mammary epithelial cells leading to a phenotype resembling triple-negative breast cancer (TNBC). p38gamma also promotes TNBC growth and metastasis by stimulating cancer-like stem cell (CSC) expansion. Moreover, p38gamma phosphorylates estrogen receptor alpha (ER) and DNA Topoisomerase II alpha, likely further contributing to TNBC phenotype. Importantly, the p38gamma pharmacological inhibitor pirfenidone (PFD) suppresses xenograft growth of K-Ras-mutated colon cancer and TNBC in nude mice. These results together indicate that p38gamma is an important therapeutic target in K-Ras mutated colon cancer and in TNBC.

We recently further investigated roles of p38gamma in tumorigenesis in genetic mouse models of colon and breast cancers. Conditional knockout (KO) of p38gamma from intestinal epithelial cells suppresses AOM/DSS-induced colon cancer and inhibits beta-catenin/Wnt pathways and systemic application of PFD shows similar effects in wild-type, but not in p38gamma KO, mice. Further, conditional p38gamma KO from mammary epithelial cells inhibits breast cancer development in a PyMT mouse model. Currently, we are studying effects of p38gamma KO on mouse pancreatic cancer development in a KPC mouse model. Because p38gamma activates several key molecules in glycolysis, we will in future exploit if p38gamma is a master activator of aerobic glycolysis, a hallmark of cancer, and thereby promotes cancer development and growth by activating metabolic reprogramming.

Visit Dr. Chen's Faculty Collaborative Database profile for additional information.

Publications

Publications of Guan Chen MD, PhD from the Faculty Collaboration Database