Our laboratory studies the molecular pathogenesis of primary brain tumors as well as brain metastases. We are particularly interested in how disturbed gene regulation mediates crucial oncogenic phenotypes.
Recent molecular profiling conducted on diffusely infiltrating gliomas, the most common brain tumor variants, has firmly implicated global epigenetic dysfunction in the process of cancer formation. In particular, highly recurrent mutations in genes such as IDH1, ATRX, and H3F3A, have been shown to induce widespread disturbances in DNA methylation and/or chromatin architecture. We are now investigating how these molecular alterations, which largely define the core molecular subgroups of glioma, dysregulate gene expression, impact genomic stability, and drive oncogenesis. Our studies apply high-throughput genomic technology as well as focused analytical methods in both in vitro and in vivo settings. We are also translating our discoveries into therapeutic strategies for these deadly tumors.
Brain metastasis of primary cancer from peripheral organ sites represents a serious and often fatal complication affecting many patients. We are now studying the transcriptional events underlying the development of brain metastasis. Our strategy employs the identification and molecular analysis of patient-matched tissue sets across a range of primary tumors metastatic to the brain. In doing so, we aim to identify key transcriptional programs and their master regulators whose involvement in the development of brain metastasis is essential. We will then model the behavior of these dysregulated gene networks in disease-relevant in vitro and in vivo systems.
Finally, we have a long-standing interest in the molecular classification of primary brain tumors as a vehicle to develop of more accurate prognostic and predictive biomarkers. In particular, we are engaged in collaborative profiling efforts designed to identify molecular, clinical, and/or radiographic factors designating disease outcome in patients with diffuse gliomas. We are also investigating how specific genetic polymorphisms predict risk for the development of specific glioma variants.