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Evaluation of the Role of Ninj1 in Neutrophil Cell Death and the Development of Inflammatory Diseases

Grant number: 24/12851-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: December 01, 2024
End date: November 30, 2027
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Dario Simões Zamboni
Grantee:Danielle Pini Alves Mascarenhas
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

Recently, it has been discovered that Ninj1 plays a crucial role in plasma membrane rupture during various types of programmed cell death, including apoptosis, pyroptosis, and necroptosis. This finding opens new perspectives for better understanding the mechanisms involved in the regulation of cell death, especially in the context of neutrophils, where such mechanisms are still poorly understood. Faced with this knowledge gap, we propose to investigate the role of Ninj1 in neutrophil cell death and NETs (Neutrophil Extracellular Traps) formation, as well as its influence on the control of intracellular pathogens. NETs play a crucial role in antimicrobial defense but also participate in the pathogenesis of autoimmune and inflammatory diseases. Currently, the molecular mechanisms underlying NETs release are insufficiently understood, underscoring the importance of investigating how Ninj1 may influence this process. Our research focuses on the central hypothesis that Ninj1 plays a fundamental role in NETs extrusion, a hypothesis supported by promising preliminary results. Demonstrating this function could not only expand our understanding of immune response regulation against pathogens but also have significant therapeutic implications, potentially enabling targeted interventions for autoimmune and inflammatory diseases.

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