In this sub-project, we aim to characterize different human intestinal macrophage populations and their metabolic signatures at single cell level in situ to depict cellular metabolic heterogeneity. We recently developed a first approach to profile central carbohydrate metabolism in single cells in situ. With this novel tool we will significantly contribute to the goal of this consortium by exploring the immunometabolic profile of macrophage populations in vivo. Using a multimodal imaging approach, we will establish the metabolic signatures of macrophages and of their neighboring cells in situ by assessing key cellular enzyme activities driving glycolysis, the pentose phosphate pathway and TCA cycle in antibody-defined single cells. We will investigate the metabolic signatures of different human macrophage populations and other tissue-resident cells in healthy and diseased tissue biopsies of patients. We will evaluate in situ findings by testing targeted metabolic interventions and their functional consequences in human tissue culture and organoids was well as in animal disease models (E. Pohl, G. Egger, T. Weichhart) for identification of immunometabolic targets in human diseases. We will compare our data to adipose tissue macrophages and depict associations with the microbiome (M. Schweiger, G. Schabbauer, C. Moissl-Eichinger). We expect that metabolic profiling of human macrophages within their physiological and pathophysiological microenvironments by multimodal analysis will provide a better understanding of their tissue heterogeneity and indicate novel therapeutic opportunities or guide clinical decision making in precision medicine.
Medical University of Vienna
Department of Laboratory Medicine
Währinger Gürtel 18-20
1090 Vienna
arvand.haschemi@meduniwien.ac.at
Haschemi Lab
Nikolina Bradarić
PhD Student
SFB member
Chuqiao Chen
PhD Student
SFB affiliated
Supriya Murthy
Postdoc, starting Oct. 2021
SFB member
Synthesis of 4-Deoxy-4-Fluoro-d-Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping. Scheibelberger L, Stankovic T, Pühringer M, Kählig H, Balber T, Patronas EM, Rampler E, Mitterhauser M, Haschemi A, Pallitsch K. Chem. Eur. J. 2023. https://doi.org/10.1002/chem.202302277.
Fluorinated Analogues to the Pentuloses of the Pentose Phosphate Pathway. Scheibelberger, L., Stankovic, T., Liepert, K., Kienzle, A., Patronas, E. M., Balber, T., Mitterhauser, M., Haschemi, A., Pallitsch, K. European Journal of Organic Chemistry 26, e202300339. 2023. https://doi.org/10.1002/ejoc.202300339.
A fingerprint of 2-[18F] FDG radiometabolites–how tissue-specific metabolism beyond 2-[18F] FDG-6-phosphate could affect tracer accumulation. Patronas EM, Balber T, Miller A, Geist BK, Michligk A, Vraka C, Krisch M, Rohr-Udilova N, Haschemi A, Viernstein H, Hacker M, Mitterhauser M. iScience (2023). https://doi.org/10.1016/j.isci.2023.108137.
d-2-Hydroxyglutarate is an anti-inflammatory immunometabolite that accumulates in macrophages after TLR4 activation. de Goede KE, Harber KJ, Gorki FS, Verberk SGS, Groh LA, Keuning ED, Struys EA, van Weeghel M, Haschemi A, de Winther MPJ, van Dierendonck XAMH, Van den Bossche J. BBA-Molecular Basis of Disease 1868. 2022. https://doi.org/10.1016/j.bbadis.2022.166427.
Metabolic rewiring controlled by c-Fos governs cartilage integrity in osteoarthritis. Matsuoka K, Bakiri L, Bilban M, Toegel S, Haschemi A, Yuan H, Kasper M, Windhager R, Wagner EF. Metabolic rewiring controlled by c-Fos governs cartilage integrity in osteoarthritis. Annals of the Rheumatic Diseases (2023). https://doi.org/10.1136/ard-2023-224002.