P30 Dr. Kramann
Dissecting pathways initiating a profibrotic and anti-angiogenic injury response in perivascular myofibroblast precursors in kidney fibrosis

Our data indicates that injury drives detachment of Gli1+ cells from capillaries triggering renal capillary rarefaction, hypoxia and myofibroblast formation as initiators of fibrosis. In an unbiased Gli1 cell-specific transcriptomic approach we identified critical pathways involved in this process that might be promising therapeutic targets. The project will utilize cell specific in vivo CRISPR/Cas9 gene editing to induce conditional loss of function mutations in these pathways using bigenic Gli1CreERt2; Cas9 mice with the ultimate goal to stop initiation of kidney fibrosis by switching Gli1+ cells from a pro-fibrotic, anti-angiogenic towards a pro-angiogenic pro-regenerative phenotype.

 

 

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