My laboratory studies the biology of breast cancer metastasis using cell culture, and animal models, followed by validation of the findings using clinical specimens. Our experimental system involves HOXB9, a transcription factor overexpressed in breast cancer, and its partner BTG2, a p53 inducible gene suppressed in breast cancer. We have demonstrated that these molecular aberrations, gain of HOXB9 expression and loss of BTG2 expression, induce tumoral secretion of cytokines and angiogenic factors into the microenvironment. These factors induce signaling pathways that promote tumor cell proliferation, migration and invasion, angiogenesis, and distal metastasis. Moreover, they also alter tumor cell fates leading to the acquisition of mesenchymal and stem-like phenotypes, which can influence tumor cell responses and resistance to radiation and other therapeutic interventions.
In collaboration with Drs. Daniel Haber and Mehmet Toner, I co-direct the cellular and molecular characterization of Circulating Tumor Cells (CTCs), which ties in very well with the overall goal of the lab to study the metastatic spread of cancer. CTCs are a rare population of heterogeneous tumor-derived cells found in the circulation that are the likely the source for distal metastatic disease. Based on the biology of tumor progression, CTCs are likely to comprise of epithelial, mesenchymal and stem-like cells. Detecting CTCs has far-reaching implications for both clinical care and cancer biology. CTCs are rare, comprising 1 in a billion cells in the blood of patients with metastatic breast cancer. Hence their isolation presents a tremendous technical challenge for existing cell separation technologies. The micro-fluidic technology developed in Dr. Mehmet Tonerâ€™s laboratory enables gentle, efficient and specific isolation of live CTCs in a single step. CTCs isolated from breast, prostate, pancreatic and lung cancer patients using this cutting edge technology will be characterized and standardized to provide a non invasive tool in early disease detection, and monitoring response/resistance to therapy; viable cells will be cultured to gain insight into the growth, drug resistance and metastatic properties of these epithelial cancers.