- Department / Institute
- Department for Vascular Biology, Institute for Stroke and Dementia Research
- Subject area
- Inflammation Research, ARDS Research, Vascular Research
- Name of supervisor
- Prof. Dr. Jürgen Bernhagen, Dr. Adrian Hoffmann
- Number of open positions
- 1
- Project title
- Chemokine-targeting CXCR4-ectodomain mimics and their potential blockingactivity in acute and chronic microvascular lung inflammation
- Language requirements
- Fluency in English
- Academic requirements
- 4-year Bachelor's plus Master's degree
- Study model
- Full doctoral study model: 36 or 48 months
- Contacts
- Prof. Dr. Jürgen Bernhagen: juergen.bernhagen@med.uni-muenchen.de
Dr. Adrian Hoffmann: adrian.hoffmann@med.uni-muenchen.de
Project description
According to the LUNG-SAFE study, 10% of all patients admitted to an ICU and 23% of those requiring mechanical ventilation fulfill the criteria of Acute Respiratory Distress Syndrome (ARDS). ARDS qualifies as a life-threatening disease with significant mortality rates ranging from 15-52% from mild to severe forms despite modern treatment strategies. The high chances of irreversible organ dysfunction due to fibroproliferative remodeling result in clinically non-acceptable morbidity rates. We face a high ARDS prevalence that was dramatically fueled by the recent COVID-19 pandemic and an unmet medical need for the development of future drug candidates to reduce the burden of ARDS to patients and society.
Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine and atypical chemokine that is a major determinant of various acute and chronic inflammatory conditions, cardiovascular diseases and cancer. MIF as well as classical chemokines such as CXCL12 orchestrate disease-amplifying immune cell trafficking and are key players in ARDS lung pathogenesis.
In our previous work in the areas of vascular inflammation, we recently characterized peptide-based mimics of the chemokine receptor CXCR4 that selectively target chemokine-mediated atherosclerotic/inflammatory effects. Based on this work, the CSC PhD project will focus on elucidating the predicted effects of such molecules as future drug candidates for ARDS. The hypothesis will be tested in well-established acute and chronic/fibrotic experimental ARDS mouse models. While our previous work concentrated on the macrovascular chronic inflammatory disease atherosclerosis, the here presented CSC project will expand into the acute/subacute and microvascular context, e.g. in lung inflammation. Furthermore, the project is based on a longstanding interdisciplinary research collaboration between Prof. J. Bernhagen, Chair of Vascular Biology at LMU and the Department of Anesthesiology at LMU University Hospital, which is one of the largest ARDS centers in Germany.