Pathways for BMP9/10 responsiveness in smooth muscle cells, critical for pulmonary hypertension and right heart failure (A02)

• Subject Area: Developmental Biology
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 268555672

Mutations in the BMPR2 pathway predispose for pulmonary hypertension (PH), but the intracellular pathways downstream of BMPR2 and the impact of smooth muscle cell (SMC) heterogeneity on PH are not fully understood. We will explore the heterogeneity of SMCs using a novel intersectional genetics approach, allowing selective gene manipulation in vascular SMCs. We will address the role of the RNA binding proteins RBPMS/2, which are BMP9/10 targets and promote formation of contractile SMCs in the intestine, but have an opposite function in pulmonary arteries. We will also investigate regulation of BMP9/10 signaling by m6A RNA modifications in PH, since inactivation of the m6A writer complex seems to protect against PH.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1213: Pulmonary Hypertension and Cor Pulmonale
• Applicant Institution: Justus-Liebig-Universität Gießen
• Project Heads: Professor Dr. Saverio Bellusci; Professor Dr. Thomas Braun