M.D. (cum laude). University of Buenos Aires, Argentina. 1981.
Ph.D. (summa cum laude). University of Buenos Aires, Argentina. Neuropharmacology. 1984.
Molecular and cellular mechanisms of brain tumor formation remain elusive. This challenges the understanding and development of clinically effective treatments for deadly brain tumors. Our research program aims to understand how brain tumors grow and invade throughout the brain, a tissue that paradoxically has no space where tumors can form. We are currently exploring the molecular basis of individual patterns of brain tumor growth and invasion. Understanding the molecular and cellular mechanisms used by brain tumor cells to grow and invade throughout the brain is allowing us to develop more effective therapeuties. We identified at least 4 different patterns used by brain tumor cells and brain tumor stem cells to grow throughout the brain. This information is used to develop specific inhibitors targeted to each mechanism, based on the molecular basis of individual growth patterns. Novel specific nhibitors are used as experimental therapies in transplantable or genetically-induced models of glioma, and in early translational phase I trials in the future. Further, we are interested in developing mathematical and physical models of brain tumor growth and invasion, to uncover the essential factors allowing brain tumor cells to form macroscopic tumors and kill patients. In addition, we are currently initiating a Phase I trial of a combined cytotoxic and immune-stimulatory gene therapy for brain tumors in adult patients; this trial is based on our own preclinical work, and is the first trial of its kind ever to be tested in human patients. Finally, we are exploring novel strategies to stimulate immune responses against brain tumors, and using nanoparticles to target individual anatomical pathways used by invading glioma cells. In summary, our research program focuses on the molecular, cellular, genetic (and hopefull in the future, mathematical and physical) basis of brain tumor growth and invasion. From experimental models we move the most successful strategies into early phase human clinical trials, the ultimate frontier of human brain tumor research.
Sanderson et al. (2012) Cytotoxic immunological synapses do not restrict the action of interferon-Î_ to antigenic target cells. PNAS, 109:7835-40
Zirger et al. (2012) Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNÎ_, perforin, and TNFÎ±, and due to the elimination of transduced cells. Molecular Therapy, 20:808-19
Puntel et al. (2011) Identification and visualization of CD8+ T cell mediated IFN-Î_ signaling in target cells during an antiviral immune response in the brain. PLoS One, 6(8):e23523
Larocque et a. (2010) Exogenous fms-like tyrosine kinase 3 ligand overrides brain immune privilege and facilitates recognition of a neo-antigen without causing autoimmune neuropathology. PNAS, 107:14443-8
Yang et al. (2010) Kupfer-type immunological synapse characteristics do not predict anti-brain tumor cytolytic T-cell function in vivo. PNAS, 107:4716-21.