Associate Director for Translational Research,
David M. Rubenstein Center for Pancreatic Cancer Research
Memorial Sloan Kettering Cancer Center
Christine Iacobuzio is an Attending Physician in the Department of Pathology, and the Associate Director for Translational Research in the Rubenstein Pancreatic Cancer Research Center. Dr. Iacobuzio’s research is focused on the fundamental mechanisms underlying metastasis using pancreatic cancer as a model tumor type. Her laboratory is unique in that it utilizes primary and metastatic tissues obtained from the rapid autopsy of cancer patients in combination with next-generation sequencing of the harvested tissues to understand the mechanisms of metastasis. This approach has led to the discovery of the distinct patterns of metastatic failure in pancreatic cancer patients, the relationship of these patterns of failure to the genetics of the primary carcinoma, the origin of distant metastases from subclonal populations that are preexistent within the primary carcinoma, and the timing of distant metastasis formation based on computational models.
The current goals for her laboratory are as follows. First, she aims to determine the extent to which subclonal genetic evolution within a primary carcinoma selects for prosurvival phenotypes with the consequence of these phenotypes being metastasis. For example, she is interested to know if subclonal genetic evolution generates one or more metastatic subclones within the primary site and if gene alterations that accumulate within metastatic subclones target specific core pathways. These functions/pathways may be targeted by a variety of genetic mechanisms both within different subclones in the same pancreatic carcinoma, and across different patients’ carcinomas, providing a definitive basis of genetic heterogeneity in cancer. This is important to know as genetic heterogeneity is believed a major reason for treatment failure yet a full understanding of heterogeneity at a fundamental level is lacking. Second, she is studying the extent to which pro-metastatic subclones have unique morphologic, immunologic and microenvironmental characteristics that distinguish them from other subclones within the same primary tumor. Unlike the first goal, these studies place greater emphasis on the role of the microenvironment as a selective force that favors the birth of metastasis-enabled cells. Finally, using a combination of rapid autopsies of a wide variety of tumor types and long-term evolution studies, she aims to determine the dynamics of Darwinian selection of human cancer cells in real time with the goal of identifying translational and therapeutic opportunities for patients.