Research Group Jakob Körbelin

Research Interests

The cerebral vasculature plays a major role in the pathogenesis of many neurological disorders. Dysfunction of the blood-brain barrier (BBB) has been related to some of the most common disorders of the central nervous system such as multiple sclerosis, epilepsy or Alzheimer’s disease. Brain endothelial cells play an important role as gate keepers of the BBB. They are essential for maintaining an intact barrier in close interaction with pericytes and astrocytes. Our aim is to investigate the potential of an endothelial-directed gene therapy of neurovascular and neurological disorders.

Our research is based on the development of safe, efficient and target-specific gene therapy vectors. The adeno-associated virus (AAV) is one of the most promising gene delivery platforms as it combines efficient gene transduction with a superior safety profile compared to many other viral vector systems. We use large randomized peptide libraries which are displayed on the surface of AAV (so-called random AAV display peptide libraries) to further diversify the natural viral tropism and to generate AAV particles with affinity for new cellular targets. By employing such AAV display peptide libraries in different screening approaches over multiple selection rounds, we are able to identify efficient and target-specific AAV-based gene therapy vectors for the brain and a variety of other tissues.

We want to bring gene therapy one step closer to the clinic by evaluating our complex techniques for the generation of tailored recombinant AAV vectors in a broad number of pre-clinical models of neurological disorders at the Institute for Experimental and Clinical Pharmacology and Toxicology. In close collaboration with the other research groups at the institute and with international partners we try to push forward the endothelial-directed treatment of neurological disorders

Collaborations

Ayal Ben-Zvi, Hebrew University of Jerusalem, Department of Developmental Biology and Cancer Research

Jan K. Hennigs, University Medical Center Hamburg-Eppendorf, Department of Pulmonology

Nasrul Hoda, Augusta University, Department of Medical Laboratory, Imaging, & Radiologic Sciences

Claus Pietrzik, Johannes Gutenberg University Mainz, Institute of Pathobiochemistry

Martin Trepel, Klinikum Augsburg, Interdisziplinäres Cancer Center Augsburg

Jasmin Wellbrock, University Medical Center Hamburg-Eppendorf, Department of Oncology