Rare Disease
TGF-β/BMP signaling in rare diseases
Functional TGF-β/BMP signaling is essential for proper tissue development and homeostasis, and mutations in this pathway underlie numerous pathologies, including the rare diseases Fibrodysplasia Ossificans Progressiva (FOP), Hereditary Haemorrhagic Telangiectasia (HHT), and Pulmonary Arterial Hypertension (PAH). By combining cellular and animal models with molecular and biomechanical approaches, we investigate how these mutations disrupt signaling and aim to translate our mechanistic insights into new therapeutic strategies.
Balanced TGF-β/BMP signaling is essential for proper tissue development and homeostasis. To uncover how disease-causing mutations alter signaling and to identify potential therapeutic strategies we use cellular models together with molecular and biomechanical approaches.
Fibrodysplasia ossificans progressiva (FOP) is driven by gain-of-function mutations in the BMP type I receptor ALK2 (ACVR1), leading to excessive BMP signaling and heterotopic bone formation in soft tissues. We investigate the composition of the receptor complex and how this aberrant signaling can be selectively modulated.
Hereditary Hemorrhagic Telangiectasia (HHT) results from mutations in ALK1 or endoglin, causing arteriovenous malformations and leaky blood vessels. Our research focuses on how impaired ALK1 signaling disturbs vascular stability and angiogenic balance.
Pulmonary Arterial Hypertension (PAH) is linked to reduced signaling through the BMP receptor BMPR2, promoting uncontrolled proliferation of pulmonary artery cells and vascular remodeling. We aim to understand how restoring BMP signaling can normalize endothelial and smooth muscle function.
Hydrocephalus
Congenital hydrocephalus is a severe condition that can impair brain development. Our research focuses on how disruptions in cellular signaling and barrier integrity may contribute to the onset and progression of this disease.