INFLAMMATION-INDUCED ALTERATIONS OF THE BONE MARROW MICROENVIRONMENT
One major goals of our research is to ultimately understand how the structural and functional integrity of the bone marrow is fundamentally altered in pathological conditions. We study whether structural defects affect tissue organization, disrupt cellular interactions and therefore promote a decline in the specialized niche function of the marrow. We investigate the cellular and molecular mechanisms by which damage is caused to inform on strategies to prevent them. We are also studying the regenerative and self-organizing processes that lead to the complete rebuilding of bone marrow tissues after myeloablative damage.
HEMATOPOIETIC MICROENVIRONMENT IN THE FETAL LIVER AND SPLEEN
During development the hematopoietic potential transits through different embryonic organs, in adulthood hematopoiesis settles in the marrow cavities of bones. Exposure to the different microenvironments is proposed to modulate the properties of hematopoietic stem cells and shape hematopoietic output. Through the use of imaging techniques, genetically modified mouse models and global analyses of gene expression we aim to characterize the different stromal cell types found in fetal liver and spleen, and define the molecular mechanisms by which the participate in hematopoietic regulation.
COMPUTATIONAL TOOLS FOR QUANTITATIVE ANALYSIS OF 3D TISSUE IMAGES
The rapid development of clearing protocols and improved microscopy techniques for organ-wide, fast 3D scanning of tissues, is driving a revolution in the way histological studies are performed. Despite major progress, one of the unresolved challenges is the extraction of quantitative information from large 3D imaging datasets using automated computational methods. In collaboration with the Computer Vision laboratory and the Data Analysis Unit at the Scientific Center for electron and Optical Microscopy of the ETH Zurich, we work on advanced tools to enable object and structure segmentation, classification and quantification in a fast and reliable manner. The goal is to apply these methods to provide a comprehensive description of the functional organization of hematopoietic tissues.
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THREE DIMENSIONAL STRUCTURE AND SPATIAL INTERACTIONS IN BONE MARROW
Proper maintenance of complex multicellular tissues not only depends on the types and numbers of cells that form them, but on their assembly into unique structural configurations. Structure and function are thus highly intertwined. We are interested in dissecting functional stromal-hematopoietic cell interactions within native microenvironments. To perform these studies we take advantage of state of the art microscopy technologies implemented in our laboratory, which enable the three-dimensional organ-wide imaging hematopoietic tissues at subcellular resolution. We further employ spatial statistics to investigate whether spatial associations are significant and therefore indicative of functional interactions