1 PhD Position in �Role of transforming growth factor signaling in PAH�
Job Offer Details
Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arteries, characterized by excessive pulmonary vascular remodeling leading to a progressive increase in pulmonary vascular resistance (PVR), progressive right ventricular hypertrophy (RVH), heart failure, and death. The pathophysiological mechanisms of PAH are complex and multifactorial.
Currently available therapies for PAH are considered to act principally via vasodilation, and although offering symptomatic benefit and some improvement in long term outcomes, their true impact on disease progression is considered limited. The development of novel therapies that directly target the fundamental processes involved in chronic pulmonary vascular remodelling and maladaptive RV structure/function represents a key aim in this disease.
In this context, recent interest has focused on the potential therapeutic application in PAH of growth factor inhibitors. The transforming growth factor (TGF) receptors together with their ligands control various processes involved in vascular remodeling, including proliferation, apoptosis, collagen turnover, which are fundamentally involved in PAH. However, the role of TGFß1 in pulmonary vascular and RV remodeling remain to be elucidated.
The role of TGFß1 in pathogenesis of experimental PAH (monocrotaline and hypoxic models) were demonstrated. However, these models do not produce the occlusive neointimal and plexiform lesions that are observed in human PAH. The combination of the vascular endothelial growth factor receptor (VEGFR) blocker SU5416 and exposure to hypoxia (SUHx) in rats lead to severe PAH and closely mimic the vascular changes seen in patients with severe PAH.
Thus, the aim of our project is to investigate the TGF/SMAD/BMPr signaling pathway and the effects of selective TGFß1 inhibitor in severe angioproliferative experimental PAH and RV failure induced by combination of SU5416 and hypoxia.
Language of the Doctoral Thesis
Requirements for Applicant
Subject Requirements (Qualification)
Type of Persons
- Curriculum vitae
- Copy of university degree
- Letter of motivation
- Language Certificate English
University / Organisation advertising the position
University / Organisation
Faculty / Institute
International Giessen Graduate School for the Life Sciences (GGL)
Supervisor of the Doctoral Thesis
Herr Prof. Dr. Ralph Schermuly
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