Spatial biology of tumor-stroma assembloids reveals that "Nothing is lost, nothing is created, everything is reorganized"
Gina Bouchard, PhD
Instructor, Department of Biomedical Data Science
Friday, March 15, 2024
11:00am - 12:00pm
James H. Clark Center, Room S360, 3rd floor next to the Coffee Shop
Zoom link
Abstract
Spatial -omics technologies must be codeveloped with quantitative methods for comparing in vitro patient-derived models with histological specimens. We propose a quantitative approach to assess the extent of resemblance between patient-derived tumor models and human tumors' cytoarchitecture. We introduce the "colocatome" as a spatial -omic cataloging statistically significant colocalizations between cell subpopulations or states, allowing for normalization and facilitating direct comparisons of spatial features between in vitro models and tissues. Our study involves colocatome analysis on multiplexed immunofluorescence images of human lung adenocarcinoma (LUAD) tumor-stroma assembloids constructed with epithelial organoids and Cancer-Associated Fibroblasts (CAFs) from the tumor edge vs core. We confirm that assembloids recapitulate LUAD's tumor-stroma cytoarchitecture, affirming the relevance of patient-derived in vitro models for studying human tumors. Following drug perturbation of assembloids, we demonstrate that CAFs protect cancer cells from targeted oncogene treatment by uniquely reorganizing cytoarchitecture, rather than promoting cellular heterogeneity or selection. We identify drug-resistant cytoarchitecture patterns from assembloids, consistent with the more aggressive histologic growth patterns of treatment-naive LUAD samples. Overall, our colocatome analysis applied to in vitro patient-derived tumor models and transferred findings to cancer specimens can serve as a functional spatial readout to predict tissue reorganization in response to cancer treatment and is generalizable to other conditions.
Bio
Dr. Bouchard received her bachelor’s degree in pharmacology and her doctorate in Radiation Science and Biomedical Imaging in the laboratory of Dr. Benoit Paquette at the University of Sherbrooke, Canada. During her thesis, Dr. Bouchard studied the effects of radiation on breast cancer cell migration and invasiveness. Dr. Bouchard received a postdoctoral fellowship from Stanford University to join the Cancer Systems Biology program with the primary goal of training cancer biologists for bioinformatics, and vice versa. During her postdoctoral research in Dr. Sylvia Plevritis' laboratory, Dr. Bouchard investigated the intercommunication between cancer cells and fibroblasts from various sites of lung adenocarcinomas using a multi-omics approach. Dr. Bouchard is currently continuing her research as an Instructor in the Department of Biomedical Data Science at Stanford. Here, she utilizes 3D patient-derived assembloids to examine metabolic reprogramming in the stroma, employing a spatial biology approach. The primary objective is to identify spatial features associated with metabolic resistance and to optimize radiotherapy in cancer patients.