Malignant brain tumors are among the deadliest of all human cancers. The focus of my research involves an integrated approach to brain tumors from basic cancer biology to preclinical studies of targeted therapeutics and translation of these approaches into clinical trial. We are interested in key signal transduction pathways that regulate tumor cell behavior, particularly in tumor invasion and angiogenesis. One key pathway is transforming growth factor-beta which acts in combination with other signaling pathways to contribute to tumor progression. Additionally, signal transduction elements have been targeted with specific therapies that may improve tumor control with reduced side effect profiles. Laboratory studies have demonstrated that these molecularly targeted therapies may be useful in brain tumor treatment when used against tumors with specific molecular fingerprints. More recently, we have investigated the roles of cancer stem cells in defining overall tumor behaviors. We have defined roles for this tumor subpopulation in radiation resistance and tumor angiogenesis through specific molecular mechanisms that may be amenable to targeted therapies. Our current studies seek to identify improved methods to target cancer stem cells.