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.

Molecular Genetics of Brain Tumors

As molecular pathologists, we have been identifying 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 -PXA), craniopharyngioma and brain metastases aiming to spark new clinical trials and to support the characterization of clinical trial specimens with validated biomarker assays. Our efforts have led to remarkable treatment responses in patients with PXA, craniopharyngioma, and meningioma and we have defined numerous new targets for brain tumor treatments.

Powerful New Tools for Characterizing Human 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 such as IDH-mutant gliomas and pituitary adenomas and to bring mass spectrometry diagnostics into advanced operating rooms to assist with iterative real time tissue characterization. We are also leading efforts in quantitative pathology along with Peter Sorger, to bring highly multiplexed tissue imaging technologies such as tissue cyclic immunofluorescence ( to the study of human cancer  .