We conduct basic medical and scientific research on two areas: 1) the mechanisms by which epithelial cancers invade and metastasize and 2) the mechanisms by which cancer cells evade immune responses.
Cancer arises in a multi-step process in which normal cells acquire mutations through the activation of oncogenes and the loss of tumor suppressor mechanisms. We are interested in examining the signaling pathways in cancer cells in order to understand the molecular events leading to tumor growth, invasion, metastasis, and immune suppression.
Crk is a small SH2 and SH3 domain containing protein and one of the most versatile genes in cells. Using these domains to assemble multi-functional protein complexes, Crk binds an astonishing number of proteins involved in cell proliferation and cell motility. The significance of Crk in human cancers has been enumerated in recent years. It is now apparent that Crk is overexpressed in several carcinomas and sarcomas, including breast cancer, lung cancer, glioblastoma, gastric cancer, synovial sarcoma, and ovarian cancer. We now know that the level of expression correlates with aggressive and malignant phenotypes and the more advanced staging of the disease. Our research employs structural biology, molecular biology, mass spectrometry, and animal cancer models in order to examine and analyze Crk and its function in invasion and metastasis.
Cell death (apoptosis) is a part of life. Each day millions of cells die and are cleared in our tissues in a non-inflammatory manner to maintain tolerance. Apoptosis is also very important in the tumor microenvironment. Highly proliferating tumors have equally high rates of apoptosis, necessitating the demand for phagocytic cells to engulf apoptotic cells. We have found that tumor cells themselves have high phagocytic activity in the tumor environment and compete with professional phagocytes (such as dendritic cells) for engulfment, as well as for their ability to mount an effective anti-tumor response. We hypothesize that tumor phagocytes produce immunosuppressive factors that prevent the immune system from killing cancer cells. Our multidisciplinary approach includes rational drug design as a way of developing a new class of anti-cancer therapeutics that target tumor phagocytes.