My primary research interests involve the molecular pathogenesis of brain tumors, particularly high-grade gliomas. The efforts of my laboratory are currently directed towards both basic science and more clinically oriented translational investigations.
microRNA (miRNA) Biology
We are particularly interested in the impact of miRNA-based gene regulation in the evolution of primary brain tumors. miRNAs are small noncoding RNAs that mediate pre-translational repression of selected genes by binding loosely complementary sequences in target mRNAs, most commonly in their 3'-untranslated regions. Numerous miRNAs have been implicated in neoplastic processes, including brain cancers like glioma and medulloblastoma. We have recently identified the miRNA miR-26a as a direct translational repressor of the tumor suppressor PTEN. Furthermore, we have demonstrated that miR-26a is amplified at the genomic level in a significant portion of high-grade gliomas and that miR-26a-mediated PTEN regulation facilitates gliomagenesis in vivo. We are currently exploring the role of other miRNAs and miRNA clusters in the development of gliomas and other tumors using a variety of in vitro techniques, as well as in vivo mouse modeling. We are also undertaking prospective screens to identify miRNA species that may be involved in glioma-relevant biological processes like cell migration and invasion. Through these investigations, we hope to identify pathogenic miRNA/mRNA interactions and the molecular networks in which they act, both of which may serve as targets for therapeutic intervention.
Molecular Pathology
As our understanding of brain tumor biology has grown, so too has the realization that each tumor class is notably heterogeneous in its molecular characteristics. Recently, large-scale analysis of genomic copy number data as well as transcriptional profiling has revealed distinct subclasses of high-grade glioma, each of which will most likely respond differently to rationally designed targeted therapies. From the standpoint of molecular pathology, the task now becomes to develop effective means by which to rapidly identify specific tumor subclasses and, in this way, facilitate the development and application of new drug trials. We are currently testing a variety biomarker sets using immunohistochemistry as well as direct mRNA and miRNA analysis. Our ultimate aim is to develop robust techniques that can be applied to paraffin-embedded material, thus ensuring broad applicability. We also intend to perform similar molecular characterization studies on medulloblastoma and other primary brain tumors.
Lab Head CV (PDF)
