ESR 7: Sanne Maas

Sanne.Maas@med.uni-muenchen.de

Instructing FPR2 and GPR32 for treatment of atherosclerosis and myocardial infarction

Research project

To create liposomes with the combined property of targeting the atherosclerotic endothelium and releasing their cargo only at sites of high shear forces.

ESR 7 will:

1. Characterise the role of FPR2 and GPR32 in mouse models of myocardial infarction.
2. Identify molecular moieties specific for the endothelium of advanced atherosclerotic lesions. Proteomics will be used to compare endothelial cells from advanced atherosclerotic lesions with endothelial cells of microvascular inflammation (e.g. acute lung injury). Complementary hereto, an in vivo phage display using a M13 phage library (2x109 individual clones) consisting of randomised linear peptides of 7 amino acids will be used. This will be done in connection with UMA
3. Liposomes will be designed and functionalised with antibodies directed to the molecular structures identified before
4. Delivery of agonists to the pro-resolving receptors FPR2 and GPR32.

Main Supervisor

Name: Oliver Soehnlein
Email: oliver.soehnlein@med.uni-muenchen

Host Institution

Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten
Poliklinik, Klinikum der Universität München
Ludwig-Maximilians-Universität München
Pettenkoferstrasse 8a , Raum E0.82
D-80336 München, Germany

Expected Results

Establish the role of two protective receptors in the endothelial cell reactivity relevant to atherosclerosis and myocardial infarction. Construct nanomedicines as based upon functionalized, tissue-specific liposomes enriched with peptides agonists to Fpr2 (or GPR32) and determine efficacy in atherosclerosis and myocardial infarction. ‘Force’ efficacy of the therapeutic by adding specific targeting exploiting phage display technology.

Planned secondment(s)

1. UMA, The Netherlands (March - April 2018): To investigate modelling of the selected linear peptides and establish potential target complementary and establish homing in other models of vascular disease (e.g. calcification) to ascertain specificity.
2. MosaMedix, The Netherlands (May 2018): To train on file patent writing and applications to protect and benefit from inventions.
3. LifeArc, United Kingdom (2019): To design of FPR2 agonists.