Ming Tsao

Research Synopsis

Molecular Basis of Lung & Pancreatic Cancer

The laboratory is focused on translational research projects in lung and pancreatic cancer, two of the most deadly cancers with overall five-year survival rates of 15% and 2-5%, respectively. Greater understanding of the molecular basis of their malignancy will provide insights for improving the early diagnosis and treatment against these diseases.

The primary goals of our lung cancer projects are to identify novel genes or proteins that are better than clinical predictors alone in predicting clinical outcome or response to therapies. We profile the gene expression and genomic aberrations of a large number of human lung cancer samples using microarray techniques, apply computational bioinformatic algorithms to identify the predictive genes or gene signatures, and validate them by realtime quantitative PCR technique. The biological functions of the predictive genes are then studied using in vitro lung cancer cell line model, primary lung cancer xenograft models and orthotopic rodent models of human lung cancers.

The primary goal of our pancreatic cancer project is to dissect the molecular basis of human pancreatic cancer, which mostly arises from the duct epithelium. Our laboratory was the first to establish primary cultures of normal human pancreatic duct cells. Immortalized cell lines derived from these primary cultures are used to study the activities of oncogenes and tumor suppressors that are commonly aberrant in pancreatic cancer. The approach provides insights into key molecular events that may be targeted to prevent and treat pancreatic cancer.. Special interest and emphasis involve the signaling of epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor receptor. These two growth factor signaling loops play important roles in the growth and metastasis of lung, pancreatic and colorectal cancer. We are also investigating the role of mutations and overexpression of these genes in the biology of these cancers.

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Recent Publications

• Qian J, Niu J, Li M, Chiao PJ, Tsao M-S. In vitro Modeling of Human Pancreatic Duct Epithelial Cell Transformation Defines Gene Expression Changes Induced by K-ras Oncogenic Activation in Pancreatic Carcinogenesis. Cancer Res 2005;65:5045-53.
• Tsao M-S, Sakurada A, Cutz J-C, Zhu C-Q, et al. Molecular and clinical predictors of response and prognostic markers of survival in patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group Trial BR.21. New Engl J Med 2006;353:133-44.
• Zhu CQ, Popova S,Brown ERS, Barsyte-Lovejoy D, et al. Integrin 11 regulates IGF-2 expression in fibroblasts to enhance tumorigenicity of human non-small cell lung cancer cells. Proc Natl Acad Sci USA 2007;104:11754-9

Graduate Students

Peiran Su