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SFB 1744:  Compartmentalized cellular networks in neurovascular diseases

Subject Area Medicine
Term since 2026
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 548585053
 
Neurovascular diseases (NVDs) are the leading cause of long-term disability, the second most common cause of death, and a major contributor to dementia worldwide. Despite their high burden, most patients lack specific treatments. Recent research has uncovered a surprising complexity in NVDs, with poorly understood mechanisms that hold promise for novel therapeutic targets. Advances in single-cell omics and imaging have revealed an unexpected cellular diversity and compartmentalization in the brain, which appear to shape disease processes. This includes (1) vascular zonation of endothelial and mural cells; (2) distinct immune interfaces such as the choroid plexus and subsets of adaptive immune cells; and (3) glial cells with compartment-specific states, including in perivascular niches. We hypothesize that NVD progression and complications are driven by compartmentalized cellular networks (CCNs) - functional networks of vascular, immune, and glial cells that support neuronal health, contribute to disease, and offer potential treatment targets. Our aim is to understand how interactions between distinct cell types within anatomical compartments influence disease course and outcome. Our strategy focuses on both chronic and acute NVDs that directly impact brain vasculature, including cerebral small vessel disease (SVD), cerebrovascular amyloidosis, ischemic stroke, and intracerebral/subarachnoid haemorrhage. We will investigate how vascular dysfunction and immune/glial responses impair neuronal function. Building on key discoveries by CRC1744 members in NVD biology, compartmentalization, and cellular responses, we will leverage existing models, tools, and technologies to systematically study these mechanisms. Our methodological approach integrates expertise from neurovascular biology, immunology, glia/stem cell biology, genetics, and data science. We will combine single-cell and spatial transcriptomics with advanced imaging and genetic tools. In addition to experimental animal models, we will conduct mechanistic studies on human iPSC-based models of the neurovascular unit, transplanted human organoids, and in-vivo multicellular recordings in patients. Harmonized models and shared platforms across projects will enable comparative analyses and strengthen collaboration. We will initially focus on ischemic NVDs and expand to haemorrhagic forms in the second funding phase. As a step towards clinical translation, later funding periods will include pre-clinical randomized trials and large animal models. Our long-term goal is to translate findings from model systems to patients and identify compartment-specific therapeutic targets. Achieving this goal requires the structure of a CRC: the complexity of NVD biology, and the technical challenges in dissecting cellular crosstalk across compartments, demand a multidisciplinary, collaborative framework with integrated methods and a joint long-term strategy for data sharing.
DFG Programme Collaborative Research Centres

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Participating University Technische Universität München (TUM)
 
 

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