Research field: Myeloid cells in inflammation and cancer
Group leader: Prof. Dr. Ir. Jo Van Ginderachter
Our mission is to use the heterogeneity of myeloid cells (MCs) as an in vivo sensor to track inflammatory responses and as a target for therapeutic intervention (Figure 1). Recent evidence (including our own) reveals that tissue-associated MCs contain different subpopulations with different ontological 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, transcriptomics, proteomics, metabolomics and functional heterogeneity of different MC subpopulations present in selected inflamed tissues, in particular in tumors (tumor-associated macrophages, myeloid-derived suppressor cells and dendritic cells), the liver (Kupffer cells), and the brain (microglia and barrier-associated macrophages or BAM).
Based on markers that allow a discrimination between selected MC subpopulations, we fully invest 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 the identification of markers for different tumor-associated macrophage or dendritic cell populations, as well as Kupffer Cell- and microglia/BAM-specific markers, to generate 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. 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.
Area of expertise
- Tumor immunology, with a particular focus on the role of myeloid cells (mainly macrophages and dendritic cells) in the tumor microenvironment.
- Liver immunology, with a particular focus on the role of tissue-resident Kupffer cells versus bone marrow-derived myeloid cells during parasitic infections (mainly Trypanosoma), bacterial infections (mainly Listeria) and sterile liver inflammation (including liver cancer). 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 versus bone marrow-derived myeloid cells during infectious inflammation (Trypanosoma, Listeria), glioma and neuronal wiring.
- The use of Nanobodies and their engineering platform for the imaging and therapeutic targeting of myeloid cells in vivo.
Global strategy of the Myeloid Cell Immunology Lab (click to enlarge)
Technology transfer potential
- Identification of myeloid cell-associated molecules as targets for therapeutic intervention
- Nanobodies for imaging and targeting of myeloid cells during various pathologies
- Bieniasz-Krzywiec P et al. Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer.
Cell Metabolism. S1550-4131(19)30428-0. 2019.
- Van Hove H et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment.
Nature Neuroscience. 22(6):1021-1035. 2019.
- Laoui D et al. The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity.
Nature Communications, 7, 13720, 2016.
- Van Overmeire E et al. M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment
Cancer Research, 76, 35-42, 2016.
- Laoui D et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population
Cancer Research, 74, 24-30, 2014.
For publications with IRC as the affiliation, click here. For all publications, click here.