Exploring the role of NADPH oxidase 2 (NOX2) in myeloproliferative neoplasms

• Applicant: Dr. Julian Baumeister
• Subject Area: Hematology, Oncology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537070058

Myeloproliferative neoplasms (MPN) are hematologic disorders characterized by abnormal proliferation of myeloid blood cell populations. Despite the advancements in MPN treatment, current treatment options are limited, highlighting the need for the development of novel therapeutic strategies. Emerging evidence, including recent findings from our own and other research groups, suggests that NADPH oxidase 2 (NOX2) may play a significant role in MPN pathogenesis, making it a potential target for therapeutic intervention. The aim of this project is to investigate the role of NOX2 in MPN and explore its potential as a therapeutic target. To achieve this, we will employ a multidimensional approach encompassing both in vivo and in vitro studies. Initially, we will assess the impact of NOX2 genetic depletion in murine MPN models in vivo, as well as in cell line models and primary cells derived from MPN patients in vitro. This comprehensive analysis will provide insights into the functional implications of NOX2 deficiency in the context of MPN. Subsequently, we will evaluate the efficacy of various pharmacologic inhibitors using three distinct in vitro MPN models. This screening process aims to identify the most promising candidates for further investigation as potential therapeutic agents. The selected inhibitors will be subjected to an in vivo efficacy assessment using a murine MPN mouse model. This crucial step will provide valuable information regarding their therapeutic potential and pave the way for future clinical applications. By deepening our understanding of the role of NOX2 in MPN and exploring its therapeutic significance, this project has the potential to pave the way for the development of innovative treatment strategies that could ultimately improve patient outcomes in the clinical management of MPN.

• DFG Programme: Research Grants