The B-Projects include the biomedical applications for the following scientific fields:
- Cardiovascular Research
- Gastrointestinal diseases
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Project B01 (Makowski/Hamm)
Characterization of the Extracellular Matrix of the Aortic Wall during the Development of Aneurysms Using Molecular and Biophysical MRI
Abdominal aortic aneurysms (AAAs) are an increasing burden for the healthcare system. The extracellular matrix (ECM) maintains the structural integrity of the aortic wall. Our preliminary work has demonstrated the potential of molecular imaging for the characterization of AAAs. In this project, we will test both novel and known approaches of molecular and biophysical magnetic resonance imaging (MRI) for the characterization of the ECM in an AAA mouse model. The aspired gain in knowledge is the identification of the most promising molecular probes and elastography techniques, or the combination of both, for estimating the risk of AAA progression/rupture.
Project B02 (Ludwig/Stangl)
Proteoglycans and Glycosaminoglycans as Targets for Noninvasive Imaging of Unstable Atherosclerotic Plaques
Rupture of atherosclerotic plaques causes life-threatening complications such as ischemic stroke and myocardial infarction. Noninvasive methods to identify plaques at risk of rupture are highly desirable to improve diagnosis and guide therapy. Glycosaminoglycans have been identified by us as a potential diagnostic target in atherosclerosis. We hypothesize that plaque instability correlates with a specific glycosaminoglycan pattern. This project aims at identifying glycosaminoglycans associated with plaque instability and evaluates their potential use as targets for the noninvasive imaging of rupture-prone atherosclerotic plaques.
Project B03 (Taupitz/Schnorr)
Targeting Extracellular Matrix Changes Induced by an Altered Homeostasis of Phosphate Metabolism
Elevated phosphate serum levels cause cardiac dysfunction. The underlying pathomechanism remains to be elucidated. Preliminary work by our group has revealed high levels of glycosaminoglycans (GAGs). This experimental project will test the hypothesis that it is possible to characterize hyperphosphatemia-induced myocardial damage in vivo using GAG-targeting imaging probes and elastography techniques. In the setting of the proposed CRC, this will be done using quantitative physical and biochemical analytical methods as references.
Project B05 (Infante-Duarte/Sack)
Investigation of Extracellular Matrix Alterations in Murine Models of Multiple Sclerosis by Molecular and Biophysical MRI
Brain development and neuroinflammatory disorders, such as multiple sclerosis (MS), are associated with alterations of the brain extracellular matrix (ECM). This project will investigate the mechanisms that lead to pathologic or proregenerative ECM changes in the brain in order to elucidate their potential for ECM-specific molecular and biophysical imaging. Therefore, magnetic nanoparticle accumulation in brain tissue of an MS mouse model will be correlated with multiscale elastography parameters. In conjunction with experiments on cell cultures and brain slices, our in vivo imaging studies are expected to reveal which biochemical and biophysical tissue properties can be used as biomarkers for ECM-directed imaging of neuroinflammation.
Project B06 (Siegmund/Kühl)
Inflammatory Activity and Targeting of the Extracellular Matrix in Inflammatory Bowel Diseases
Inflammatory bowel diseases are lifelong disorders characterized by an intermittent course. The recurrent nature is associated with accumulation and frequent remodeling of the extracellular matrix (ECM), causing fibrosis and stenosis. Glucosaminoglycans (GAGs) are involved in cell-matrix interactions and are strongly expressed in the ECM. Project B06 will address the effect of immune cells on intestinal ECM remodeling employing GAG-specific probes and in vivo imaging in order to uncover distinct compositions and distributions of GAGs in intestinal inflammation and ECM accumulation.
Project B07 (Asbach/Braun)
The Extracellular Matrix as Target for Biophysical and Molecular Imaging of Inflammation and Fibrosis of the Liver
There is a high demand for noninvasive diagnostic imaging of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Both diseases cause remodeling of the extracellular matrix (ECM). Preliminary work by our group shows a high sensitivity of magnetic resonance elastography (MRE) to such changes. The aim of this project is to analyze the potential of advanced magnetic resonance elastography (MRE) methods and ECM-targeted probes for imaging-based characterization of disease-specific changes of ECM structures. For this, we will correlate results from MRE, histology, and biochemical analysis of resected human liver tissue, ECM phantoms, and NAFLD and NASH animal models.
Project B08 (Schellenberger/Guo)
Full Mechanical and Extracellular Matrix Profile of the Cancerous Liver during Tumor Progression and after Treatment with Novel Theranostic XTEN Fusion Proteins
During tumorigenesis, remodeling of the extracellular matrix (ECM) in the inflamed surrounding tissue is of great importance for local tumor growth and metastatic spread. Matrix metalloproteinases (MMP) are regulators of such structural alterations, which modify mechanical tissue properties that are detectable by elastography. In this project, we will design completely E. coli-expressible, theranostic XTEN fusion proteins activated by MMP that are overexpressed in the tumor environment and investigate the correlation between mechanical properties and ECM composition in cancerous liver of a mouse model during tumor progression and after treatment with fusion Proteins.