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Medical University of Graz

Research focus

Projects at the Institute of Pathophysiology and Immunology are clinically oriented and aim at understanding human disease processes. A particular focus is put on the role of cellular and molecular interactions among tissue-resident cell types in disease pathophysiology. The institute focus on human diseases and primary cell-based models/in vivo analyses aim at clinical translation for improving disease diagnosis and therapy monitoring.

Tissues comprise heterogeneous cell populations of mesenchymal, epithelial and hematopoietic origins. Mesenchymal-derived endothelial cells line inner surfaces of blood vessels and fulfill an important function in selecting the nature of molecules and cells attracted to specific tissues. Moreover, fibroblasts, adipocytes, chondrocytes and osteoblasts play key roles in tissue homeostasis and epithelia cells fulfill important barrier and innate immune functions at body surfaces. Additionally, several subtypes of immune cells of the mononuclear phagocyte system (MPS) reside within tissues. These hematopoietic stem cell-derived leukocytes not only include blood monocytes and dendritic cells that enter tissues via transmigration through endothelia during steady-state and inflammation, but also include tissue-resident macrophages and dendritic cells that are regenerated locally. Epithelial, endothelial and MPS cells sense pathogens, nutritional and danger signals in tissues, and dysregulation thereof critically contribute to disease pathophysiology. Cells in tissues interact for preventing inflammation (e.g. via regulatory T cells and MPS cells), thereby inhibiting diseases processes. Endogenous and exogenous factors (e.g. nutrition) can lead to dysregulation thereof. The tissue-resident pool of MPS cells is critical for orchestrating innate and adaptive immune responses for inducing and preventing diseases.

Projects at the Institute of Pathophysiology and Immunology are highly interactive and synergistic, aiming at identifying basic principles of disease pathophysiology by focusing on selected tissues. Specifically, (1) understand how tissue-resident cells interact for promoting disease processes in model diseases in the central nervous system, adipose tissue, cancerous and autoimmune/inflammatory lesions; (2) identify metabolites and metabolic networks that control these disease-associated/homeostatic cellular interactions in specific tissues to genetic and environmental factors, including diet and microbes, and to identify metabolic diseases that are influenced by genetic and dietary/microbial factors; (3) furthermore, given their tissue and disease-specific functions (i.e. promotion/inhibition of disease processes), we study the cell intrinsic and environmental molecular mechanism underlying MPS differentiation/polarization from hematopoietic stem cells; and concomitant specific functions in orchestrating innate immunity and tolerance.

Several unique institute core methods and experimental platform have been established for studying disease pathophysiology effectively at molecular, cellular and systemic levels. These allow highly interactive projects within the institute infrastructure. Among these are measurements of tissue (e.g. adipose), endothelial and immune cell parameters; cutting edge primary cell methods in cancer research such as the generation of cell lines from carcinomas; chorio-allantoic membrane (CAM) assay for studying normal and cancerous human tissues under in vivo-like conditions and ex vivo differentiation models of human innate and adaptive immune cells for studying cancer cell/pathogen-immune cell interactions.  Moreover, gene transfer methodology in primary cells allow for studying the role of individual signaling pathways in specific cell types within complex tissues such as carcinomas (e.g. carcinoma-associated MPS and mesenchymal cells). An in house core facility of in situ hybridization and immunohistochemistry/ immunofluorescence facilitates these clinically-oriented projects. Additionally, various methods in modern cellular and molecular biology are established within our infrastructure.

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