PI’s: Rabindra Tirouvanziam & Greg Gibson
Project Date: March 4, 2016
This project aims to identify therapeutic targets in pathogenic polymorphonuclear neutrophils (PMNs), an inflammatory subset that destroys airways in cystic fibrosis (CF). To this end, we leverage our ability to produce pathogenic CF airway PMNs in massive amounts ex vivo, in a unique transmigration model (Tirouvanziam group) that uses airway fluid from CF patients as an apical chemoattractant and conditioning milieu. Our technological expertise (Gibson and Dahlman groups) is used to profile critical RNAs in these PMNs as they dynamically acquire a pathogenic fate in the model (Aim 1), and to deliver specific RNAi constructs via optimized nanoparticles to modulate them transcriptionally (Aim 2). This project tackles a highly complex and vexing clinical issue (refractoriness of CF PMNs to therapy) with an innovative approach (RNA targeting).
Margaroli, C., Tirouvanziam, R., “Neutrophil Plasticity Enables the Development of Pathological Microenvironments: Implications for Cystic Fibrosis Airway Disease”, Mol Cell Pediatr 3, 38 (2016). https://doi.org/10.1186/s40348-016-0066-2.