CROSS-TISSUE ULTRASTRUCTURAL IMAGING FOR DISCOVERING FIBROTIC DETERMINANTS AND ACTIONABLE TARGETS IN DC/TBD

Awardee: Alfredo Rodríguez

Institution: National Autonomous University of Mexico (UNAM)

Grant Amount: $62,158

Funding Period: February 1, 2025 - January 31, 2026


Summary:

Fibrosis of the lung and liver are threatening complications for patients with DC/TBD, however the composition of the fibrotic niche and potential targets for treating and preventing it are virtually unknown. In this proposal we have assembled an international team from Mexico (UNAM) and the USA (Mayo Clinic) that will examine the composition of the fibrotic niche. Using high precision microscopy, we will generate multidimensional images of primary fibrotic lung and liver from patients with DC/TBD and using computational tools we will reconstruct the fibrotic niche in these tissues, importantly without tissue dissociation and maintaining its architecture. We will use markers for detecting multiple cell types, including pro-fibrotic immune cells, followed by state-of-the-art spatial transcriptomics using Xenium technology. Our combined approach will provide an unprecedented single cell resolution of the DC/TBD critical fibrotic tissues and will help us propose actionable targets for preventing and treating fibrosis.

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Molecular Pathogenesis and Epigenetic Rescue of Novel Human Models of ZC4H2-associated rare disorders.

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Charting WDR45-dependent genes for neurodegeneration at a single-cell resolution