Projects
The research program is divided into four main research areas. Area A investigates the resident and Area B non-resident molecular and cellular mechanisms of aortic disease. Area C focuses on preclinical and clinical translational research. Area D contains the central projects.
A particular focus has been set on aortic valve stenosis, aortic aneurysm, and aortic dissection.
Projects
The projects were selected for this consortium to collaboratively address the following fundamental questions:
- Which danger signals, mediators, and cytokines govern the pathological interaction in-between circulating cells and between non-resident and resident cells?
What are the key cellular players in the innate and adaptive immune processes that are involved in aortic disease? - How do red blood cells, platelets, and perivascular adipocytes contribute to aortic disease?
- What is the role of endothelial cell specificity, redox homeostasis, mechanotransduction, and extracellular vesicle release for the initiation and progression of aortic disease?
- Which specific signaling pathways in interstitial smooth muscle cells drive aortic disease?
- How do resident cell death pathways influence aortic wall inflammation and extracellular matrix composition?
- What are the detailed mechanisms and consequences of modification of the extracellular matrix in the aorta?
- Which are the underlying genes involved in human aortic disease and how can we translate animal models to the human diseases?
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Research Area A - Non-resident effectors of aortic aneurysm and aortic valve disease
The Research Area A will investigate cells infiltrating and surrounding aortic tissue, including regulatory T cells, platelets, macrophages and perivascular adipose cells. It will focus on how they mediate aortic tissue damage on the molecular level and how they orchestrate a pro-inflammatory response through activation and detection of danger signals and physical stimuli. Specifically, TLR3, RIG-I, CD40, S1P and extra-nasal olfactory receptor 2 will be explored and if these pathways can be therapeutically used.
Research Area B - Resident effectors of aortic aneurysm and aortic valve disease
The Research Area B will investigate the genetic footprints and proteins that drive endothelial heterogeneity in the aortic tissue and the pathways influencing aortic disease. It focuses on the analysis of intra- and intercellular communication via non-coding RNA and how they induce inflammation and calcification during aortic disease development. It investigates the molecular events that promote smooth muscle cell fate and phenotype switch in aortic disease.
Additionally, it will elucidate how hyaluronan and fibrillin variants interfere with inflammation, growth factors and structural remodelling, as extracellular matrix components are essential in aortic diseases.
24
Projects
43
Project leaders
25
PhD Students in the iRTG
Research Area C - Preclinical and clinical translation
The ultimate goal of the consortium is to improve prevention, detection and treatment of aortic disease. For this, translation of preclinical findings to patient care is essential and requires human induced pluripotent stem cells, 3D cell organoids, small and large animal models, as well as human studies in order to holistically perform disease modelling, prediction of diesease progression, disease phenotyping, diagnostics, risk stratification and therapeutic interventions. Projects in research area C are dedicated to this translational focus.
Research Area D - Central projects
