Transition to Metastatic State: Lung Cancer, Pancreatic Cancer and Brain Metastasis

Metastasis embodies the whole-organism pathophysiology of cancer. The spread of cancer cells beyond the primary tumor site is responsible for the majority of cancer deaths and is the most overt expression of cancer’s complex evolutionary dynamics. Intimately related to the intricate processes of development and immunity, the transition from locally invasive to metastatic cancer also poses a major scientific hurdle. Recent technological and computational advancements enable dynamic, multidimensional, multiplanar analysis of multiple tissues. We are applying these advances to clinical samples with the aim of generating a high-resolution spatiotemporal tissue atlas of the most lethal cancers in the United States: lung cancer, pancreatic cancer, and metastases of the central nervous system. Our approach is to obtain high-quality human biospecimens from surgical resections, biopsy, or autopsy of primary and disseminated tumors. Samples are interrogated using single-cell and single-nucleus RNA sequencing as well as spatially informative multiplexed molecular profiling using protein and RNA in situ hybridization–based technologies. Integration, analysis, and presentation of these datasets will be undertaken with the goal of generating human tumor atlases of value to the entire cancer research community.

Principal Investigators


Dr. Dana Pe’er is Chair of the Computational and Systems Biology Program and Scientific Director of The Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center at Memorial Sloan Kettering Cancer Center. She develops novel computational methods to characterize regulatory circuit dynamics at the single-cell level in the context of complex tissues such as the tumor microenvironment. She received a Ph.D. in Computer Science at The Hebrew University of Jerusalem and trained as a postdoctoral fellow with Dr. George Church at Harvard University. Dr. Pe’er has been recognized with a number of honors including a Burroughs Wellcome Fund Career Award, an NIH Director’s New Innovator Award, an NIH Director’s Pioneer Award, and the Packard Fellowship in Science and Engineering. She currently serves on the editorial board of the journal Cell and the organizing committee of the Human Cell Atlas project, co-leading computational analysis for this project.


Dr. Christine Iacobuzio-Donahue is a board-certified Anatomic Pathologist with specialty training in gastrointestinal pathology and cancer genetics. She currently serves as an Attending Physician in Pathology, Director of the David M. Rubenstein Center for Pancreatic Cancer Research, and Director of the Last Wish Program at Memorial Sloan Kettering Cancer Center. Her lab employs a variety of models and methods, including a strong emphasis on genomic and bioinformatics analyses of human primary and metastatic pancreatic cancer tissues obtained from rapid autopsies, mouse models of pancreatic cancer, and, most recently, the development of a long-term evolutionary model system for functional analyses of clonal evolution and adaptive mechanisms. Dr. Iacobuzio-Donahue is the recipient of an R35 Outstanding Investigator Award and maintains a collaboration with the American Museum of Natural History funded by the Kleberg Foundation to develop novel tools and analytics for the evolutionary biology of cancer.