Tumor-associated macrophages are promising effector cell populations for cancer elimination, targetable by metabolic, intracellular checkpoints beyond receptor-ligand systems at the cell surface. In our previous PhD/MD tandem project, we found that complementary to our research in macrophages, synthetic ligands for the nuclear heme/iron-regulated transcription factor REVERBA regulate expression of NK cell receptors, which are activatory (NCR1) or inhibitory (LAG3) in the synapse with CRC cells. The current MD project will functionally validate these receptor-ligand systems in 3D cocultures of primary NK cells and CRC patient-derived organoids using physiological iron-based ligands (e.g. Fe3+ hemin) in combination with antibodies targeting these two candidate NK receptors. Read-out assays will comprise flow cytometry measuring production of chemo/cytokines, proliferation and cytotoxicity. Patient tissues will be stained by immunohistochemistry. The project will be jointly supervised by PD Burgermeister and Profs. Ebert/Cerwenka (all at Medical Faculty Mannheim).
Please send your application to
elke.burgermeister@medma.uni-heidelberg.de;
matthias.ebert@medma.uni-heidelberg.de;
martin.schneider@memda.uni-heidelberg.de