Authors
Posey, R. R., Ozkan, A., Man, Y., Feitor, J. F., Jiang, A., Ji, J., LoGrande, N. T., Kyprianou, C., Howley, A. M., Budnik, B., Lee, J. D., Chou, D. B., Ingber, D. E.
Abstract
Damage to the vascular endothelium is a major contributor to acute radiation injury in multiple organs that underlies acute radiation syndrome (ARS), yet there are no FDA-approved radiation countermeasures targeting endothelial cells. Use of kinome-scale CRISPR screens performed in cultured human vascular endothelial cells isolated from different organs identified CLK2 as a potential radioprotective target. Pharmacological inhibition of CLK2 using TG003 and Cirtuvivint protected these endothelial cells against radiation injury and reversed its effects across the transcriptome and phospho-proteome. Human Organ Chip models of human intestine and lung that contain organ-specific epithelium and microvascular endothelium faithfully replicated clinical features of ARS when exposed to radiation, which were prevented when treated with CLK2 inhibitors. Thus, CLK2 inhibitors may represent a new class of radiation countermeasure drugs that can protect multiple organs against radiation-induced toxicities in patients with ARS.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Nov 2025.
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