Our laboratory at Dana-Farber Cancer Institute is a basic and translational oncology laboratory focused on studying pancreatic cancer and other RAS-driven malignancies. We utilize genomic, functional genetic, molecular and cell biology approaches to understand the genetics and biology of pancreatic cancer and to identify novel therapeutic strategies to evaluate in patient-derived models or genetically engineered mouse models of the disease. We actively collaborate with clinical, laboratory and computational colleagues to perform multi-disciplinary basic and translational research.

Pancreatic cancer is a devastating disease and is currently the third leading cause of cancer-related death in the United States. There is an urgent need for new therapies to improve the lives of pancreatic cancer patients. Our lab utilizes functional genetic screens and computational approaches to discover cancer cell vulnerabilities and to identify new biomarker-linked therapeutic targets in pancreatic cancer. We leverage human organoid models and genetically engineered mouse models of pancreatic cancer to investigate the mechanisms of cancer cell dependency on these new targets, with the ultimate goal of advancing new drug development programs with academic and industry collaborators. The KRAS oncogene is mutated in the majority of pancreatic cancers and is the major driver of this disease. We use pancreatic cancer as a model system to study how KRAS mediates cancer cell proliferation and survival and drives tumor progression, and we have a particular interest in identifying synthetic lethal vulnerabilities with the KRAS oncogene that may represent new therapeutic avenues. Moreover, with the recent development of a novel class of direct KRAS inhibitors, we are actively studying mechanisms of resistance to these inhibitors using functional genetic approaches.

Our laboratory also utilizes genomic and functional approaches to understand the molecular and phenotypic heterogeneity of pancreatic cancer. We collect serial tumor biopsies and blood samples from pancreatic cancer patients throughout their treatment course to study how genetic and biologic features of a patient’s tumor impact treatment response and disease progression. We have extensive experience in culturing human organoid models of gastrointestinal cancers and have developed a translational research program to investigate ex vivo therapeutic response to inform improved therapeutic selection. Moreover, we utilize DNA and RNA sequencing as well as single cell genomic studies to define the genetic, cellular and immunologic features that drive the aggressive course of this disease. Through serial studies of patients throughout treatment with standard and experimental therapies, we seek to track the evolution of these features and define mechanisms of response and resistance to therapy.