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.
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.