Ming Zhang

The main focus of my research program is to study roles of tumor suppressors in normal development and in breast and prostate cancer progression, focusing on Maspin and an Ets transcription factor PDEF. Maspin is a unique member of SERPIN family that plays roles in normal tissue development, tumor metastasis, and angiogenesis. Genetic studies by my laboratory using maspin transgenic and knockout mice demonstrated an important role of maspin in normal mammary, prostate, and embryonic development. Recently, we have identified several new properties of maspin. As a protein that is present on cell surface, maspin controls cell-ECM adhesion. This function is responsible for maspin-mediated suppression of tumor cell motility and invasion. We have also discovered that maspin is involved in the induction of tumor cell apoptosis through a mitochondrial death pathway. The long-term goals of these projects are to elucidate the molecular mechanisms by which maspin and PDEF control tumor metastasis and to identify their physiological functions in development. Another focus of research in Zhang lab is to identify immune components that control breast cancer metastasis. Chronic inflammation not only increases neoplastic transformation but also drives the inhibition of the immune response in a protective negative-feedback mechanism. Suppressive immune cells are recruited to the sites of inflammation and function to inhibit both innate and adaptive immune responses, enabling tumor tolerance and unmitigated tumor progression. To study the interplay between tumor and immune cells, Zhang lab has developed a unique animal model of breast cancer that reproduces different stages of breast cancer bone metastasis. Molecules that control tumor-immune cell interaction and immunosuppression have been identified. We are currently studying roles of these genes in tumor-driven evolution that control chronic inflammation and immunosuppression.