Overview

Our lab seeks to understand the molecular logic underlying the initiation and progression of primary brain tumors in order to gain new insights into neurodevelopment and neurophysiology that can contribute to improved treatment and diagnosis of these diseases. Glioblastomas, the most common and deadly primary brain tumors, display signature genetic lesions that perturb the activity of genes that normally regulate essential developmental and homeostatic processes in the central nervous system. In particular, the most common mutations found in glioblastomas result in constitutive activation of receptor tyrosine kinase (RTK) and Pi-3 kinase (PI3K) signaling pathways. Yet, how these mutations drive tumorigenesis is unclear, and how to effectively target these pathways therapeutically remains to be determined. Our research program is designed to discover new regulators of gliomagenesis using multidisciplinary genetic and molecular approaches.

To investigate RTK and PI3K dependent gliomagenesis, we created a Drosophila glioblastoma model in which constitutive co-activation of RTK and PI3K pathways gives rise to malignant, neoplastic glial tumors with many pathogenic features of human glioblastoma. To find new genes that govern glial tumorigenesis, we performed genetic screens using this Drosophila model, from which we isolated several novel kinases that are required for neoplastic glial proliferation. Human orthologs of these novel kinases have been assessed for involvement in glioblastoma using bioinformatics, neuropathology, and functional analysis in human tumors and mammalian glioblastoma model systems. Our results reveal that several novel kinases are subject to genetic mutation and/or altered expression in human tumors. Ongoing studies of these kinases are aimed at elucidating their roles in tumorigenesis and normal brain development in both Drosophila and mammalian systems. Our research also demonstrates that particular types of glial progenitor cells are prone to neoplastic transformation. Ongoing studies of glial cells are aimed at characterizing signals that drive their tumorigenic transformation and at identifying biomarkers that define these cell types.

Academic Appointment

• Assistant Professor, Department of Pharmacology, Emory University School of Medicine

Education

Research