Over the years, Patrick De Baetselier’s/Jo Van Ginderachter’s cellular immunology group has developed several experimental model systems that allow a detailed study of the mechanisms governing immune modulation in both normal and pathological conditions. In-house disease models include parasitic infections, such as African trypanosomosis and helminth infection, and cancer. More recently, the field of innate immunity, in particular the immunobiology of myeloid cells (MCs), became a central research topic.
MCs (including monocytes, macrophages and dendritic cells) are crucial innate effectors, immunomodulators and/or antigen presenting cells that can acquire different functional activation states depending on which immune and microbial stimuli they are exposed to. As such, MCs represent interesting targets for intervention during inflammatory/anti-inflammatory processes. Moreover, tools to monitor the activation/differentiation state of MCs would allow to use these cells as in vivo sensors in prognosis and thera(g)nosis of pathologies, as well as in therapy follow-up and screening of immunomodulators.
Our strategic vision is to use the heterogeneity of MCs (mainly monocytes, macrophages and dendritic cells) as an in vivo sensor to track inflammatory responses and as a target for therapeutic intervention. In the past, we have mainly been focused on heterogeneity of tissue-associated monocytic cells at the level of their activation states.
Recent evidence (including our own) suggests that tissue-associated MCs contain different subpopulations, including resident and recruited monocyte-derived cells that can both differentiate into antigen presenting cells upon activation/inflammation. Thus, we are gradually shifting the focus to heterogeneity at the level of different subpopulations of MCs present in selected inflamed tissues, in particular in the liver (Kupffer cells) and tumors (hypoxic and normoxic tumor-associated macrophages). Also the so-called myeloid-derived suppressor cells (MDSCs) represent an important research focus.
Based on markers that allow discriminating selected MC subpopulations, we will fully invest in the development of tools to visualize and modulate the in vivo differentiation, recruitment and function of selected MC subpopulations in inflamed tissues. These include the generation of transgenic mice allowing tracking and ablating of selected MC populations to evaluate their role in distinct models of liver injury and tumor growth. We will also fully exploit the strategic advantage of Nanobodies as tools for in vivo imaging and therapeutic targeting of MCs.
The main inflammatory diseases under study are (i) infectious diseases, with an important focus on African trypanosome infections, (ii) inflammation, with an important focus on liver inflammation, and (iii) cancer. Through collaborative networks, we are also studying a range of other inflammatory diseases such as atherosclerosis, rheumatoid arthritis and pulmonary inflammation, as well as associated pathological features (such as anemia).
Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progressionChittezhath M, Dhillon M, Lim J, Laoui D, Shalova I, Teo Y, Chen J, Kamaraj R, Raman L, Lum J, Thamboo T, Chiong E, Zolezzi F, Yang h, Van Ginderachter J, Poidinger M, Wong A, Biswas SIMMUNITY, 41, 815-29, 2014 Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage populationLaoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J, Morias Y, Movahedi K, Houbracken I, Schouppe E, Elkrim Y, Karroum O, Jordan B, Carmeliet P, Gysemans C, De Baetselier P, Mazzone M, Van Ginderachter JCANCER RESEARCH, 74, 24-30, 2014 Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the hostSalmon D, Vanwalleghem G, Morias Y, Denoeud J, Krumbholz C, Lhommé F, Bachmaier S, Kador M, Gossmann J, Dias F, De Muylder G, Uzureau P, Magez S, Moser M, De Baetselier P, Van Den Abbeele J, Beschin A, Boshart M, Pays ESCIENCE, 337, 463-6, 2012 Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophagesMovahedi K, Schoonooghe S, Laoui D, Houbracken I, Waelput W, Breckpot K, Bouwens L, Lahoutte T, De Baetselier P, Raes G, Devoogdt N, Van Ginderachter JCANCER RESEARCH, 72, 4165-77, 2012
Jo Van Ginderachter
PhD Student: Vrije Universiteit Brussel, Belgium, 1990
Staff Scientist: Vrije Universiteit Brussel, Belgium,2003
Staff Scientist VIB since January 2009
VIB Group Leader since October 2012
Patrick De Baetselier
PhD: Vrije Universiteit Brussel, Brussels, Belgium, 1977
Postdoc.: Weizmann Inst., Rehovot, Israel, 1977-80
VIB Group leader since 1995
Expert scientist since July 2012