Stress Responses in Cancer Development and Progression
We focus on understanding a fundamental challenge in tumor biology: how tumor cells develop their most aggressive behaviors and the mechanisms that they use to resist even the most sophisticated therapeutic regimens. One biological program that we focus on in this area is a potent adaptive mechanism: what has been classically called the heat shock response. So powerful is this program that it is used by even single cell organisms to survive scorching heat waves and other caustic environmental challenges. Our work has revealed that highly aggressive tumors across a broad range of tumor types co-opt the activity of heat shock factor 1 (HSF1), the dominant transcriptional regulator of this ancient survival program. The HSF1 transcriptional program differs when activated in cancer versus when it is activated in heat shock – how are the programs different, how are the programs regulated, how are tumor adaptive responses conscripted in cancer, how can the HSF1 program be modulated for therapeutic benefit. We use chemical and genetic approaches to address these questions in a range of cancer types including the most aggressive forms of cancer - melanoma and those of the brain, pancreas, ovary, breast and lung.
Molecular Genetics of Brain Tumors
As molecular pathologists, we are eager to determine the molecular drivers of brain tumors and viable new therapeutic targets. We use genomic tools in our studies and are developing a range of diagnostic, prognostic and therapeutic biomarkers and cell line models of brain tumors. We work on meningioma, low grade pediatric gliomas (such as ganglioglioma and pleomorphic xanthoastrocytoma), craniopharyngioma and brain metastases aiming to spark new clinical trials and to support the characterization of clinical trial with validated biomarker assays.
New Tools for Characterizing Brain Tumors
We are using high-powered imaging techniques to investigate the function of brain tumors. Along with a close collaborator (Nathalie Agar) who is a chemist and an expert in mass spectrometry imaging, we are implementing a range of mass spec imaging techniques to investigate the molecular pathology of brain tumors and to attempt to bring mass spectrometry diagnostics into the operating room to assist with iterative real time tissue characterization. We have strong interests in a range of new ways of imaging and characterizing brain tumors.