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IBEC Seminar: Xavier Rovira-Clavé
miércoles, diciembre 21, 2022 @ 11:30 am–1:30 pm
Epitope barcoding and subcellular high-plex imaging reveal clonal tumor patch behaviors
Xavier Rovira-Clavé, PhD
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. In this seminar I will present our recent development of epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI), for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small-cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. Thus, EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity and it is posed to help reveal principles and mechanisms of tissue developmental processes, in both normal and malignant growth, that will thus accelerate therapeutic discoveries.
Dr. Xavier Rovira-Clavé is an instructor in the laboratory of Professor Garry Nolan in the Department of Microbiology and Immunology at Stanford University, where he develops and applies multiparameter technologies to study tissue biology in models of cancer and infectious diseases. In 2016, he received his PhD in Immunology from the University of Barcelona under the supervision of Dr. Enric Espel and Dr. Manuel Reina. He also trained for a year in cancer biology studies as a visiting PhD student in the group of Dr. Gregory Emery at the University of Montreal. He has published 12 articles, including some in leading journals such as Cancer Cell and Immunity. He holds 3 granted patents. He has received 5 competitive fellowships, including the prestigious LLS Career Development Award and the EMBO postdoctoral fellowship. His areas of research include cancer, the immune system, and infectious diseases. His technical expertise includes highly multiplexed tissue imaging (spatial proteomics), single-cell assays, molecular biology approaches, cell culture, in vitro co-culture systems, engineered tumors, murine models, genome editing, bioconjugation strategies, assay automation, and single-cell spatial data analysis. His recent research efforts have been focused in the development of imaging technologies to subcellularly locate structurally unmodified drugs at the nanometer scale, track subclonal growth in situ, and co-detect multiple biomolecular species (RNA, DNA, and protein) to enable new understanding of spatial structures at the molecular, cellular and tissue levels with the long-term goal to improve disease management.