Contents
Current Projects
Dynamic profiling of the glioma kinome
Targeted kinase inhibitors represent a promising alternative to standard cytotoxic treatments for gliomas, including glioblastoma (GBM). But use of brain-penetrant drugs in combinations designed to overcome compensatory resistance mechanisms will likely be necessary to improve outcomes. Preclinical studies can aid identification of effective drug combinations. We investigate the molecular mechanisms of kinase inhibitor resistance using genetically-engineered mouse (GEM) models and human patient-derived xenografts (PDX). In particular, we focus on the molecular mechanisms by which the kinome adapts to short- and long-term drug exposure.
Cellular and epigenetic biology of glioma stem cells
Glioma stem cells (GSCs) from human glioblastoma (GBM) are resistant to radiation and chemotherapy and may drive disease recurrence after therapy. Understanding the genesis of GSCs will be critical to the design of novel therapeutic approaches to manage GBM. We investigate the molecular mechanisms of GSC development using genetically-engineered mouse (GEM) models and human patient-derived xenografts (PDX). In particular, we focus on the molecular mechanisms by which astrocytes, the most abundant glial cell type in the mammalian brain, de-differentiate into GSC after acquiring oncogenic mutations in core glioblastoma signaling pathways.
Techniques we use include:
- Next-generation sequencing including RNA-seq and whole-genome sequencing
- Multiplexed inhibitor beads mass spectrometry (MIB-MS)
- Live cell imaging
