Research projects

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1. Protein tyrosine phosphatases as negative regulators and novel targets in collateral growth

Project leader: Kai Kappert
Co-workers: Daniel Hackbusch, Janine Krüger
Collaborations: Ivo Buschmann, Nora Gatzke, André Dülsner (Department of Cardiology/ Center for Cardiovascular Research), Markus Dagnell, Arne Östman (Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institute, Stockholm, Sweden)

Project description:
Protein tyrosine phosphatases (PTPs) are dephosphorylating enzymes with primarily negative impact on tyrosine signal transduction. This project will characterize the dynamic regulation and function of PTPs during cerebral collateral growth/ arteriogenesis in a model of 3-vessel occlusion. Furthermore, in a proof-of-concept approach the role of PTPs in arteriogenesis is being tested by pharmacological intervention using PTP-antagonists. We hypothesize that PTP-inhibition and thus disinhibition of tyrosine-phosphorylation in receptor tyrosine kinases will lead to an increase of vascular proliferation and consecutively to enhanced cerebral blood flow. Taken together, the project aims at demonstrating that PTPs represent novel targets for treatment of cerebral occlusive vascular disease.

2. Role of protein tyrosine phosphatases in high-fat diet induced insulin resistance

Abbildung: Schematische Darstellung, dass Protein Tyrosin Phosphatasen (PTPs) den Status der Insulinrezeptor-Phosphorylierung und konsekutiv die nachgeschaltete Signaltransduktion maßgeblich beeinflussen.
Schematische Darstellung, dass Protein Tyrosin Phosphatasen (PTPs) den Status der Insulinrezeptor-Phosphorylierung und konsekutiv die nachgeschaltete Signaltransduktion maßgeblich beeinflussen.

Project leader: Kai Kappert
Co-worker: Janine Krüger
Collaborations: Christian Böhm, Christiane Sprang, Ulrich Kintscher (Institute of Pharmacology, Center for Cardioascular Research); Heike Meyborg, Philipp Stawowy (German Heart Center Berlin); Frank Böhmer (Institute of molecular cell biology, Friedrich-Schiller-University Jena)

Project describtion:
Diabetes and the metabolic syndrome are major risk factors for the development and progression of cardiovascular disease, including atherosclerosis. On a molecular level, obesity-linked insulin resistance has been attributed to a post-receptor deficiency. Recent data suggest protein tyrosine phosphatases (PTPs) significantly impacting on insulin receptor signal transduction (see Figure). In this research project the tissue-specific regulation and function of PTPs will be analyzed in an animal model of high-fat diet induced insulin resistance in vivo. Besides analyzing the impact of PTP-inhibitors in vivo, a precise characterization of PTPs is performed in insulin-sensitive cells in vitro. Aim of the project is to establish PTPs as novel targets in the treatment of insulin resistance.