Tissue-associated MCs contain different subpopulations with different ontogenetic origin, including embryonic yolk sac and fetal liver-derived resident macrophages and adult bone marrow-derived recruited MCs (mainly monocytes, monocyte-derived macrophages, neutrophils and dendritic cells). Evidence is mounting that these MC subpopulations perform distinct functions in health and disease. Thus, we focus on studying (epi)genomics, (single cell) transcriptomics, proteomics, metabolomics and functional heterogeneity of different MC subpopulations present in selected homeostatic or inflamed tissues, in particular in tumors (tumor-associated macrophages, myeloid-derived suppressor cells and dendritic cells), the liver (Kupffer cells), and the brain (microglia subsets and barrier-associated macrophages).
These cutting-edge molecular and genetic technologies allow the discovery of novel functionalities and markers in MC subsets, based on which we fully invest in the development of innovative tools to visualize and modulate these cells’ in vivo differentiation, recruitment and function in inflamed and diseased tissues. These tools include the generation of novel transgenic mouse strains that allow the tracking, modulation and ablation of selected MC populations, providing unprecedented insights in the role of these MCs in homeostasis and in distinct models of tumor growth and liver or brain injury. We also aim to develop original 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 (radionuclides, gold- or magnetic nanoparticles) and drugs that can remediate the inflammatory disease outcome and be translated readily into the clinic.
• Tumor immunology, with a particular focus on the role of MCs (mainly macrophages and dendritic cells) and regulatory T cells (Treg) in the tumor microenvironment.
• Liver immunology, with a particular focus on the role of tissue-resident Kupffer cells versus bone marrow-derived MCs during parasitic infections and sterile liver inflammation. Knock-in mice to specifically study the role of Kupffer cells were generated.
• Brain immunology, with a particular focus on the role of tissue-resident microglia and barrier-associated macrophages versus bone marrow-derived MCs in various brain compartments, either during steady-state or during infectious inflammation and cancer.
• The use of Nanobodies and their engineering platform for the imaging and therapeutic targeting of myeloid cells in vivo.
Technology Transfer Potential
• Identification of MC-associated molecules as targets for therapeutic intervention
• Identification of Treg-associated molecules as targets for therapeutic intervention
• Nanobodies for imaging and targeting of myeloid cells during various pathologies
• Cell therapy based on the use of tumor-infiltrating cells (mainly DCs)
• Single cell technologies
• Nanobody technology
• Transgenic mice