Mehta Laboratory

Shwetal Mehta, PhD, Principal Investigator

Laboratory Overview

Glioblastoma Multiforme (GBM), the most common form of malignant primary brain tumor, is notoriously resistant to radiation and chemotherapy. The median survival after treatment is only 9-14 months, and the prognosis for patients with these tumors has not changed significantly over the last decade. The aggressive nature of this cancer highlights a dire need for novel targeted therapies.

Aberrations in the regulatory network controlling fate choice decisions of stem/progenitor cells during development have been the leading cause of brain tumors and many other cancers. Recent studies have discovered a highly tumorigenic subpopulation of cells that reside within the tumor mass with stem/progenitor-like properties. Although these cells represent only a small percentage of glioma cells, they tend to be resistant to therapy and have the ability to self renew. One of the current approaches for targeted therapies is to identify and drug critical factors and/or pathways specifically expressed in the glioma stem cells.

The stem/progenitor-like cells found in glioma tissues express several developmentally important transcription factors. One such factor is Olig2, a central nervous system-specific factor important for gliogenesis and for formation of certain subtypes of neurons. We recently have shown that Olig2 is critical for glioma formation in a genetically-relevant mouse model. Importantly, we found that targeting Olig2 can radiosensitize human glioma cells in a p53-dependent manner.

The goal of the Mehta Laboratory is to elucidate the regulatory network of genes critical for glioma formation and their resistance to therapy. This will greatly augment our ability to identify a druggable factor that could be targeted for glioma therapy. The initial focus of the laboratory will be to identify the molecular mechanism involved in Olig2-dependent tumor initiation, growth, maintenance, and its ability to resist radiation and chemotherapy. Specifically, we will attempt to understand how Olig2 opposes the tumor suppressor functions of p53 and promotes cell proliferation.