Ming-sound Tsao

Biography

Ming-Sound Tsao FRCPC, MD Professor Contact information Pathology Toronto General Hospital 200 Elizabeth St. Rm 11E-424 Toronto Ontario M5G 2C4 Phone: 416-340-4737 Fax: 416-340-5517 Email: ming.tsao@uhn.ca Research location: Toronto General Hospital/Research Institute (UHN) Primary Research Area: Cancer Secondary Research Area: Molecular & Cell Biology Research Statement: My primary research interest is in understanding better the genomic and molecular abnormalities in lung and pancreatic cancer, such that we can improve the accuracy of our diagnosis and treatment of these deadly cancers. Comprehensive analysis of these tumors at gene sequence, gene copy number and proteomics levels may provide new “integrated” understanding of the molecular pathology of these tumors.               Ming-Sound Tsao FRCPC, MD Professor Contact information Pathology Toronto General Hospital 200 Elizabeth St. Rm 11E-424 Toronto Ontario M5G 2C4 Phone: 416-340-4737 Fax: 416-340-5517 Email: ming.tsao@uhn.ca Research location: Toronto General Hospital/Research Institute (UHN) Primary Research Area: Cancer Secondary Research Area: Molecular & Cell Biology Research Statement: My primary research interest is in understanding better the genomic and molecular abnormalities in lung and pancreatic cancer, such that we can improve the accuracy of our diagnosis and treatment of these deadly cancers. Comprehensive analysis of these tumors at gene sequence, gene copy number and proteomics levels may provide new “integrated” understanding of the molecular pathology of these tumors.              

Research Interest

Lung cancer (LC) and pancreatic cancer (PC) have 5-year survival rates of 16% and 5%, respectively. Both cancers are highly metastatic, with ~65% LC and ~80% PC patients diagnosed at advanced incurable stage. Few effective targeted therapies are available to treat LC patients, and none for PC patients. The long term goals of my research program are to improve the diagnosis and treatment of LC and PC patients, by better understanding of their biology, molecular pathology, and heterogeneity. The overarching hypotheses are: 1) cancer cells as defined by their aberrant genomes, interact with cancer stroma matrix/fibroblasts to contribute to heterogeneity in LC/PC growth, metastasis and drug responses; 2) genes/proteins that drive malignancy in these cancers are good targets for developing novel diagnostics and therapeutics. Using resources/models we have developed, we will address 3 key areas of research priorities in LC and PC: 1. Tumor cell-stroma/matrix interactions driving malignancy in LC and PC: There is strong evidence that carcinoma associated fibroblasts (CAFs) and extracellular matrix (ECM) play crucial roles in cancer development, but the mechanism is still poorly understood. The main goals of this aim is to study the complex interactions between matrix proteins and their receptors and the impact on tumor growth and metastasis. Our studies have focused on integrin alpha 11, a receptor for fibrillar collagens, and dissecting functional or phenotypic heterogeneity among CAFs. 2. Genes and pathways driving LC and PC malignancy: Our primary goal in LC research has been to identify genes or proteins that are predictive of poor prognosis in lung cancer patients who have had their tumors resected by surgery. We use established LC cell lines as in vitro models, large number of patient-derived xenografts (PDX) as in vivo models, snap-frozen and paraffin embedded human lung cancer tissues as primary tumor model, and orthotopic implantation of lung cancer cells in immune deficient mice as in vivo model to evaluate the biology and metastatic potential of lung cancer cells. Patient or PDX tumor samples are used to identify tumor-associated mutations, gene expression changes and gene copy number aberrations that correlate with poor clinical outcome. Additional functional studies are performed on cell lines with different metastatic potential. Similar approaches are used to study the molecular basis of pancreatic duct cells carcinogenesis and metastatic progression. These studies are conducted using a unique near normal human pancretic duct epithelial (HPDE) cells, a large number of pancreatic PDX models and their cell lines.  3. Targetable pathways and mechanisms of resistance to targeted therapies: The diversity and complexity of genetic/phenotypic aberrations in LC and PC may underlie the challenge of target therapies. Using the large number of PDX models and matching organoids lines derived from these genomically characterized PDX and patient tumors, we are identifying more effective biomarkers to personalized the treatment of LC/PC patients, and to mitigate/overcome the development of resistance to targeted therapies.