Julia Sauer

Identification of a NUAK1/2 Inhibitor as a Macrophage-Polarizing Compound by a Machine Learning-Based Phenotypic Cell Painting Screen

Johanna B. Brüggenthies-Brunner, Jakob Dittmer, Julia Sauer, Sarah Groetzner et autres

Disease-associated macrophage states contribute to the pathogenesis of numerous inflammatory disorders. While small molecule-mediated macrophage repolarization represents a promising strategy to restore homeostasis, current approaches often rely on predefined molecular markers and may therefore overlook previously unrecognized modulators of macrophage plasticity. To …

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Metabolic adaptations of inflammatory macrophages govern ferroptosis susceptibility via the GCH1–BH4–iNOS axis

Julia Sauer, Patricia P. Ogger, Jasmina Dukic, A Nessensohn et autres

In inflammatory tissue niches, macrophages encounter intense oxidative stress due to their own production of reactive oxygen and nitrogen species as part of antimicrobial defense. Our findings reveal that inflammatory macrophages deploy distinct, context-dependent redox-protective mechanisms to survive this self-inflicted stress, thereby …

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B77-10 Disrupting the CTGF-MMP7 Axis in Pulmonary Fibrosis: A Novel High-affinity Antibody Outperforms Pamrevlumab in Patient-derived Models

Muriel Lizé, M Myzithras, Fidel Ramírez, R Sheehan et autres

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with significant clinical burden characterized by aberrant epithelial remodeling and excessive extracellular matrix deposition. Connective tissue growth factor (CTGF/CCN2), a key mediator of fibrogenesis, is consistently upregulated in IPF and is …

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Disrupting the CTGF–MMP7 Axis in Pulmonary Fibrosis: A Novel High-Affinity Antibody Outperforms Pamrevlumab in Patient-Derived Models

Maria Myzithras, Fidel Ramírez, Ryan Sheehan, Priyanka Gupta et autres

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant epithelial remodeling and extracellular matrix deposition. Connective tissue growth factor (CTGF), is upregulated in IPF and linked to disease onset and progression. However, the recent failure of pamrevlumab, an …

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Redox-Driven Metabolic Adaptations in Macrophages : Links to Disease and Cell Death

Julia Sauer

published

iPSC-derived macrophages: An in vitro model to study human disease-relevant macrophage biology

Julia Sauer, Daniela Schloesser, Katja Koeppen, Katrin Fundel‐Clemens et autres

Human macrophages differ from their mouse counterparts in multiple metabolic pathways, surface protein expression, and transcription factor biology. Monocyte-derived macrophages (MDMs) from blood are generally used to study human macrophage biology in vitro. However, the use of MDMs as a human macrophage …

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Role of Ferroptosis in the interplay between metabolically distinct macrophages and lungs cells in the context of Idiopathic Pulmonary Fibrosis

Julia Sauer, Christoph H. Mayr, Lukasz Miloslaw Boryn, Patricia P. Ogger et autres

Idiopathic Pulmonary Fibrosis (IPF), a major global health issue, is marked by epithelial dysfunction, fibroblast activation, extracellular matrix accumulation, and macrophages playing crucial role in the deranged communication. Macrophage phenotypes, defined by distinct metabolic states, have been shown to impact neighboring cells, …

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Insights into the Identification of iPSC- and Monocyte-Derived Macrophage-Polarizing Compounds by AI-Fueled Cell Painting Analysis Tools

Johanna B. Brüggenthies, Jakob Dittmer, Eva Maria Garrido-Martin, Igor Zingman et autres

Macrophage polarization critically contributes to a multitude of human pathologies. Hence, modulating macrophage polarization is a promising approach with enormous therapeutic potential. Macrophages are characterized by a remarkable functional and phenotypic plasticity, with pro-inflammatory (M1) and anti-inflammatory (M2) states at the extremes …

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Diverse potential of secretome from natural killer cells and monocyte-derived macrophages in activating stellate cells

Julia Sauer, Agnes A. Steixner-Kumar, Svenja Gabler, Maciej Motyka et autres

Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune …

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Application of human iPSC-derived macrophages in a miniaturized high-content-imaging-based efferocytosis assay

Sarah Bitzer, Mozhgan Dehghan Harati, Karim Christian El Kasmi, Daniela Schloesser et autres

Macrophages play a pivotal role in drug discovery due to their key regulatory functions in health and disease. Overcoming the limited availability and donor variability of human monocyte-derived macrophages (MDMs), human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) could provide a promising …

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Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis

Daniela Schloesser, Laura Lindenthal, Julia Sauer, Kyoung‐Jin Chung et autres

Progressive accrual of senescent cells in aging and chronic diseases is associated with detrimental effects in tissue homeostasis. We found that senescent fibroblasts and epithelia were not only refractory to macrophage-mediated engulfment and removal, but they also paralyzed the ability of macrophages …

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