Macrophage Metabolism in Liver Regeneration and Disease

This sub-project explores how metabolic compartmentalization within macrophages supports their essential roles during liver regeneration and in pre-disease states, such as metabolic dysfunction-associated steatohepatitis. Liver regeneration, a rapid and highly coordinated process, is often harnessed in clinical practice through surgical interventions, a common treatment for various liver diseases. During regeneration, resident Kupffer cells and infiltrating monocyte-derived macrophages are critical for driving inflammation, supporting tissue remodeling, and resolving inflammation to restore liver function. On the molecular scale, metabolic processes must ensure the availability of energy and precursor molecules, but the spatial and temporal organization of the involved metabolic pathways remains poorly understood.

We aim to uncover how macrophage metabolism drives their diverse functions, focusing on processes at the smallest scales—within individual cells and their subcellular compartments. We hypothesize that different macrophage populations dynamically compartmentalize metabolic pathways to meet functional demands. This work employs macrophage-specific mouse models (with G. Schabbauer and T. Weichhart), surgical and dietary interventions (with O. Sharif), in vivo stable isotope tracing, metabolic activity assays (with A. Haschemi), and intravital imaging techniques. By mapping and manipulating these processes across macrophage populations in healthy and pre-diseased states, this research will reveal how metabolic compartmentalization shapes macrophage functions. These insights aim to advance our understanding of liver diseases and support the development of innovative therapeutic strategies.

Anne Miller

Medical University of Vienna
Center of Pathobiochemistry & Genetics
Währingerstrasse 10
1090 Vienna

anne.miller@meduniwien.ac.at
Miller Lab

Research Publications

Miller A, York E, Stopka S, Martínez-François JR, Regan MS, Agar NYR, Yellen G; Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation. (2023) Nature Metabolism https://doi.org/10.1038/s42255-023-00890-z

York E, Miller A, Stopka S, Martínez-François JR, Hossain MA, Baquer G, Regan MS, Agar NYR, Yellen G; The dentate gyrus differentially metabolizes glucose and alternative fuels during rest and stimulation. (2023) J Neurochem https://doi.org/10.1111/jnc.16004

Patronas EA, Balber T, Miller A, Geist B, Michligk A, Vraka C, Krisch M, Rohr-Udilova N, Haschemi A, Viernstein H, Hacker M, Mitterhauser M; A fingerprint of 2-[18F]FDG radiometabolites – how tissue-specific metabolism beyond 2-[18F]FDG-6-phosphate could affect tracer accumulation. (2023) iScience https://doi.org/10.1016/j.isci.2023.108137

Azzimato V, Chen P, Barreby E, Morgantini C, Levi L, Vankova A, Jager J, Sulen A, Diotallevi M, Shen J, Miller A, Ellis E, Rydén M, Näslund E, Thorell A, Lauschke V, Channon K, Crabtree M, Haschemi A, Craige S, Mori M, Spallotta F, Aouadi M; Hepatic miR-144 drives fumarase activity preventing NRF2 activation in obese livers. (2021) Gastroenterology https://doi.org/10.1053/j.gastro.2021.08.030

Klebermass EA, Mahmudi M, Geist B, Pichler V, Vraka C, Balber T, Miller A, Haschemi A, Viernstein H, Hacker M, Mitterhauser M; If it works, don’t touch it? A cell-based approach to study 2-[ 18 F]FDG Metabolism. (2021) Pharmaceuticals https://doi.org/10.3390/ph14090910

Kremslehner C*, Miller A*, Nica R, Nagelreiter I, Narz M, Golabia B, Vorstandlechner V, Mildnera M, Lachner J, Tschachler E, Ferraragh F, Klavins K, Schosserer M, Grillari J, Haschemi A, Gruber F; Imaging of metabolic activity adaptations to UV stress, drugs and differentiation at cellular resolution in skin and skin equivalents – Implications for oxidative UV damage. (2020) Redox Biololgy https://doi.org/10.1016/j.redox.2020.101583, *Equal contribution

Wilson JL, Nägele T, Linke M, Memel F, Fritsch S, Mayr HK, Cai Z, Katholnig K, Sun X, Fragen L, Miller A, Haschemi A, Popa A, Bergthaler A, Hengstschläger M, Weichhart T, Weckwerth W; Inverse Data-Driven Modeling and Multiomics Analysis Reveals Phgdh as a Metabolic Checkpoint of Macrophage Polarization and Proliferation. (2020) Cell Reports https://doi.org/10.1016/j.celrep.2020.01.011

Kremslehner C, Miller A, Nica R, Lachner J, Nagelreiter I, Mildner M, Tschachler E, Haschemi A, Gruber F; Automated immuno-histo-enzymatic investigation of metabolic enzyme activity in cryosections of skin and epidermal equivalents. (2019) Journal of Investigative Dermatology https://doi.org/10.1016/j.jid.2019.07.255

Miller A, Nagy C, Knapp B, Laengle J, Ponweiser E, Groeger M, Starkl P, Bergmann M, Wagner O, Haschemi A; Exploring Metabolic Configurations of Single Cells within Complex Tissue Microenvironments. (2017) Cell Metabolism https://doi.org/10.1016/j.cmet.2017.08.014

Linke M, Pham HT, Katholnig K, Schnöller T, Miller A, Demel F, Schütz B, Rosner M, Kovacic B, Sukhbaatar N, Niederreiter B, Blüml S, Kuess P, Sexl V, Müller M, Mikula M, Weckwerth W, Haschemi A, Susani M, Hengstschläger M, Gambello MJ, Weichhart T; Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression. (2017) Nature Immunology https://doi.org/10.1038/ni.3655