Broad Institute of MIT & Harvard - 415 Main Street, Cambridge, MA 02142, Auditorium and Zoom (See below for full information)
Spatial and temporal dynamics of immune cell interactions
In this thesis, I discuss spatial and temporal methods for studying immune cell interactions.
First, I will discuss Slide-TCR-seq, a method developed for measuring T cell receptor (TCR) sequences in the tissue context. T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic TCRs. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires. Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression. Our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses. Second, I will discuss an application of Slide-TCR-seq to study immunological aging in the thymus in human and mouse contexts, as well as strategies for regeneration.
Thesis Supervisor:
Fei Chen, PhD
Assistant Professor, Stem Cell & Regenerative Biology, Harvard University Core Institute Member, Broad Institute of MIT & Harvard
Thesis Committee Chair:
Peter Kharchenko, PhD
Gilbert S. Omenn Associate Professor of Biomedical Informatics, Harvard University
Thesis Readers:
Catherine Wu, MD
Professor of Medicine, Harvard Medical School
David Scadden, MD
Principal Investigator, Altos Labs San Diego Institute of Science, Gilbert S. Omenn Associate Professor of Biomedical Informatics, Harvard University
Shiv Pillai, MD, PhD
Investigator Ragon Institute of MGH, MIT and Harvard, Mass General Research Institute Professor of Medicine Harvard Medical School
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