The strategic vision of the Myeloid Cell Immunology lab is to use the heterogeneity of myeloid cells (MCs, mainly monocytes, macrophages and dendritic cells) as an in vivo sensor to track inflammatory responses and as a target for therapeutic intervention.
We study (epi)genomics, transcriptomics, proteomics, metabolomics and functional heterogeneity of different MC subpopulations present in selected inflamed tissues, in particular in tumors (subsets of tumor-associated macrophages and dendritic cells), the liver (Kupffer cells) and the brain (microglia and other resident brain macrophages, such as those in the brain’s barriers like meninges and choroid plexus).
Based on markers that allow a discrimination between selected MC subpopulations, we fully invested in the development of innovative tools to visualize and modulate the in vivo differentiation, recruitment and function of selected MC subpopulations in inflamed tissues. These include in particular transgenic (knock-in) mice allowing the tracking and ablation of selected MC populations. Such tools will reveal the role of these MCs in homeostasis and in distinct models of tumor growth and liver or brain injury.
In addition, we aim to develop original MC-targeting strategies to overcome inflammation-associated immunopathology of infectious and non-infectious diseases. In this regard, we fully exploit the strategic advantage of nanobodies, i.e. camelid-derived single-domain antibody fragments, and their engineering platform as tools for in vivo MC-targeted delivery of imaging agents and drugs that can remediate the inflammatory disease outcome and be translated readily into the clinic.
- Identification and validation of tumor-associated macrophage (TAM) / tumor-associated dendritic cell (TADC)-associated molecular targets that have an impact on tumor progression and that are suitable for therapeutic intervention.
- Development of a TADC-based vaccination strategy to prevent tumor relapse and metastasis outgrowth. In addition, we aim to elucidate the mechanism of vaccinations using distinct TADC subsets.
- Delineation of the involvement of barrier macrophages, microglia and monocyte-derived macrophages in the brain in shaping neuronal circuits under steady-state and in orchestrating inflammatory responses during infectious and sterile-inflammation and brain tumor (glioma) progression.
- Delineation of the contribution of liver MC, including liver-recruited monocyte-derived macrophages and liver-resident Kupffer cells, to liver injury during (i) infection, (ii) drug, toxin, fibrosis, metabolic disease-induced hepatitis, and (iii) primary hepatocellular carcinoma and liver metastasis. In addition, we aim to delineate which KC-derived molecules play an essential role in the distinct pathologies under study.
- Development of strategies for diagnostic and therapeutic targeting of Kupffer cells, microglia, monocyte-derived macrophages and tumor-supporting TAM, based on in-house generated nanobodies targeting selected MC markers.