The landscape of stress responses in the tumor microenvironment

Billions of years of evolution through changing environments led organisms to develop an arsenal of cytoprotective pathways to promote their survival under stressful conditions. One such pathway is the heat shock response. We have shown that tumors can hijack the master regulator of the heat shock response, and subvert this pathway to promote their own survival, at the expense of their host. In our lab we use patient samples, mouse and tissue culture models to decipher the mechanisms by which normal cytoprotective pathways such as the heat shock response are subverted to support malignancy.

Molecular mechanisms of stromal reprogramming

In tumors, a combination of environmental cues and signals from neighboring malignant cells lead to reprogramming of normal cells in the tumor microenvironment. We strive to identify these signals and find ways to perturb them. Using molecular and bioinformatics tools, we look at patterns of epigenetic modifications and post-transcriptional regulation in the tumor microenvironment. We study the effect of reciprocal interactions between cancer cells and normal cells on these patterns, and how these interactions contribute to the hallmarks of cancer.

Stromal heterogeneity and therapeutic resistance

In addition to the diversity of cell types present within the tumor, there is heterogeneity within different cell types in the tumor microenvironment. Subtypes of cells within the tumor stroma have distinct cellular morphologies and cell surface markers. This intratumor diversity has a major impact on tumor evolution and therapeutic resistance. Our lab examines this diversity and and its effects on the evolution of aggressive, treatment-resistant tumors.