The Integrated Stress Response (ISR) is a set of cellular pathways that consists of upstream regulatory kinases (PERK, GCN2, HRI, PKR) that respond to such stresses to suppress protein translation and while activating key downstream transcription factors, such as ATF4, that restore cellular homeostasis. We have discovered that the ISR is strongly upregulated in pancreatic cancer and contributes to tumor growth and therapy resistance. We are working to understand the role of the ISR in cancer and target it for therapeutic gain.

Use genetic, chemical-genetic and small molecule approaches to inhibit the ISR in cancer cell lines and determine effects on metabolism, cell growth and survival.

Medical students would work with graduate students, technicians, and/or postdocs in the laboratory to test a set of novel tools to control this pathway. Special methods employed include immunoblotting, immunoprecipitation, live cell imaging, immunohistochemistry, pharmacology, cell culture, genomic editing, and mouse models, depending on the student's interest.

There are also opportunities for students who are interested in looking at patient samples for markers of these processes and to help us plan for an eventual clinical trial.