CNS Tumor Biology and Blood-Brain Barrier
My laboratory focuses on the cellular and molecular biology of primary brain tumor malignancy with the combined goals of defining basic mechanisms and translating these discoveries into experimental therapeutics. We are particularly interested in glioma cell growth regulation, tumor-associated angiogenesis, and cytoprotection. We focus a great deal of attention on the role of soluble growth factors and their receptors in malignant progression of human gliomas. An example is the multifunctional cytokine, angiogenic factor, and cytoprotective factor - scatter factor/hepatocyte growth factor (SF/HGF) and its receptor c-met. Studies are presently underway to determine the SF/HGF-dependent cell signaling pathways that are operational in human gliomas. Differential gene expression analysis is being used to identify novel genes that are regulated by specific growth factors in gliomas. Ribozyme-based methods of inhibiting growth factor and growth factor receptor expression are being used to determine basic mechanisms of action and for experimental therapeutics.
We are also interested in developing novel gene delivery strategies applicable to brain and brain tumors. We recently developed endothelial-cell-based gene transfer approaches to deliver immune-activating cytokines and other secreted gene products to brain tumors for anti-tumor therapy and as tools to understanding the function of host cytokine expression within gliomas. Endothelial cell-based cytokine gene delivery has proceeded to clinical trial in patients with recurrent malignant brain tumors. Gene transfer of neurotrophic factors to brain is also being explored in animal models of brain injury.