Fabian Schumacher

Fabian Schumacher
Freie Universität Berlin | FUB · Institute of Pharmacy

Dr. rer. nat.
Researcher, Lecturer, Co-Head of MS Core-Facility Subunit

About

166
Publications
20,783
Reads
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1,670
Citations
Citations since 2016
128 Research Items
1583 Citations
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20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
Additional affiliations
January 2014 - August 2020
University Hospital Essen
Position
  • PostDoc Position
October 2013 - December 2013
Universität Potsdam
Position
  • PostDoc Position
June 2009 - September 2013
German Institute of Human Nutrition
Position
  • PhD Student
Description
  • Mass spectrometric determination of DNA adducts originating from the Brassica constituent 1-methoxy-3-indolylmethyl glucosinolate (neoglucobrassicin) in vitro, in animal models and in humans
Education
June 2009 - September 2013
German Institute of Human Nutrition
Field of study
  • Nutritional Toxicology
October 2003 - May 2009
University of Leipzig
Field of study
  • Chemistry

Publications

Publications (166)
Article
Full-text available
Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced...
Article
Full-text available
Major depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of ~ 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate th...
Article
Full-text available
Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice wi...
Article
Full-text available
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, esp...
Article
Full-text available
Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes. However, the impact of cell-intrinsic ceramide...
Preprint
Full-text available
Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes. However, the impact of cell intrinsic ceramide...
Article
Full-text available
Antidepressants have been reported to enhance stroke recovery independent of the presence of depressive symptoms. They have recently been proposed to exert their mood-stabilizing actions by inhibition of acid sphingomyelinase (ASM), which catalyzes the hydrolysis of sphingomyelin to ceramide. Their restorative action post-ischemia/reperfusion (I/R)...
Article
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A fine balance of regulatory (Treg) and conventional CD4+ T cells (Tconv) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the Treg/Tconv balance. However, our understanding of ho...
Article
Two challenges in topical drug delivery to the skin include solubilizing hydrophobic drugs in water-based formulations and increasing drug penetration into the skin. Polymeric core-multishell nanocarrier (CMS), particularly the novel biodegradable CMS (bCMS = hPG-PCL1.1K-mPEG2k-CMS) have shown both advantages on excised skin ex vivo. Here, we inves...
Article
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Background Ex-vivo lung perfusion (EVLP) is a save way to verify performance of donor lungs prior to implantation. A major problem of lung transplantation is a donor-to-recipient-transmission of bacterial cultures. Thus, a broadspectrum anti-infective treatment with sphingosine in EVLP might be a novel way to prevent such infections. Sphingosine in...
Article
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Starch binding domain-containing protein 1 (STBD1) is an endoplasmic reticulum (ER)-resident, glycogen-binding protein. In addition to glycogen, STBD1 has been shown to interact with several proteins implicated in glycogen synthesis and degradation, yet its function in glycogen metabolism remains largely unknown. In addition to the bulk of the ER,...
Article
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Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium chann...
Article
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In brief Hochrein et al. report that inflammatory T cells express high levels of GLUT3. Ablation of GLUT3 curtailed Th17-cell-mediated immune responses and protected mice from autoimmune colitis and encephalomyelitis. GLUT3-dependent glucose metabolism controls the generation of nucleo-cytosolic acetyl-CoA and the epigenetic regulation of cytokine...
Preprint
Full-text available
Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice wi...
Article
Full-text available
Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscle, has insulin-sensitizing and anti-inflammatory properties. Sphingosine 1-phosphate (S1P) is reported to act as effector of diverse biological actions of Adn in different tissues. S1P is a bioactive sphingolipid synthesized by the phosphorylation of s...
Article
Background Sphingolipids, in particular ceramides, play an important role in the pathogenesis of cystic fibrosis (CF) lung disease. Ceramides seem to be dysregulated in people with CF (PWCF): An elevated ratio of ceramides C16Cer/ C24Cer has been linked to inflammation and disease severity. CFTR modulators might influence sphingolipid dysregulation...
Preprint
Full-text available
In the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), a better understanding of the underlying mechanisms is essential to reduce morbidity and mortality and treat post-COVID-19 disease. Here, we analyzed alterations of sphingolipids and their metabolizing enzymes in 125 men and 74 women tested...
Article
Voriconazole (VRC) pharmacokinetics, in particular its complex metabolism, is still not fully understood which challenges its optimal therapeutic use. To increase knowledge on the pharmacokinetics of this antifungal drug, it is essential to broaden the perspective and expand in vitro and clinical in vivo investigations in particular to aspects such...
Article
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Sphingosine‑1‑phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating m...
Article
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Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46–...
Article
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Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, is generated from sphingosine by sphingosine kinases (SPHKs) 1 and 2 and is metabolized to ∆2-hexadecenal (∆2-HDE) and ethanolamine phosphate by S1P lyase (S1PL) in mammalian cells. We have recently demonstrated the activation of nuclear SPHK2 and the generation of S1P in the nucleus of lun...
Article
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As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles...
Article
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Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein–Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having re...
Article
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Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an...
Article
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Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3+ regulatory T cell frequencies among CD4+ T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to...
Preprint
Functional inhibitors of acid sphingomyelinase are clinically used as anti-depressants since ~60 years. Here, we show that acid sphingomyelinase inhibition by the antidepressants amitriptyline, fluoxetine and desipramine protects from ischemia/reperfusion and elicits a profound brain remodeling response with increased angiogenesis, improved blood-b...
Article
Full-text available
Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechani...
Preprint
Full-text available
Background: Ex-vivo lung perfusion (EVLP) systems like XVIVOâ are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial...
Article
Insulin is the main anabolic hormone secreted by β-cells of the pancreas stimulating the assimilation and storage of glucose in muscle and fat cells. It modulates the postprandial balance of carbohydrates, lipids and proteins via enhancing lipogenesis, glycogen and protein synthesis and suppressing glucose generation and its release from the liver....
Article
Here were report the combination of biocompatible click chemistry of ω-azidosphinganine with fluorescence microscopy and mass spectrometry as a powerful tool to elaborate the sphingolipid metabolism. The azide probe was efficiently synthesized over 13 steps starting from L-serine in an overall yield of 20% and was used for live-cell fluorescence im...
Article
Infection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis towards CXCL1 ex vivo. Additionally, we...
Article
Full-text available
The acid sphingomyelinase (ASM)/ceramide system exhibits a crucial role in the pathology of major depressive disorder (MDD). ASM hydrolyzes the abundant membrane lipid sphingomyelin to ceramide that regulates the clustering of membrane proteins via microdomain and lipid raft organization. Several commonly used antidepressants, such as fluoxetine, r...
Article
Full-text available
Acid sphingomyelinase (ASM) is a potential drug target and involved in rapid lipid signalling events. However, there are no tools available to adequately study such processes. Based on a non cell-permeable PtdIns(3,5)P2 inhibitor of ASM, we developed a compound with o-nitrobenzyl photocages and butyryl esters to transiently mask hydroxyl groups. Th...
Article
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Ceramide transfer protein (CERT) mediates non‐vesicular transfer of ceramide from endoplasmic reticulum to Golgi apparatus and thus catalyzes the rate‐limiting step of sphingomyelin biosynthesis. Usually, CERT ligands are evaluated in tedious binding assays or non‐homogenous transfer assays using radiolabeled ceramides. In this study, we present a...
Article
Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mec...
Article
Full-text available
Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine p...
Article
Full-text available
Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tgfb) that is restricted to the forebrain to rule out any systemic effects of Asm over...
Article
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Background & Aims The cause of fatty liver is multifactorial, including genetic and environmental factors. Currently, only a few genetic variants explain the heritability of the disease. QTL analysis of mouse strains enables the identification of genes causing complex human diseases. In a backcross of New Zealand obese (NZO) and C57BL/6J (B6) mice...
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Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. H...
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Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid c...
Article
Full-text available
Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis...
Article
Long-chain fatty aldehydes are present in low concentrations in mammalian cells and serve as intermediates in the interconversion between fatty acids and fatty alcohols. The long-chain fatty aldehydes are generated by enzymatic hydrolysis of 1-alkyl-, and 1-alkenyl-glycerophospholipids by alkylglycerol monooxygenase, plasmalogenase or lysoplasmalog...
Article
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Background/aims: Pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus) are of utmost clinical relevance in patients with cystic fibrosis, chronic obstructive pulmonary disease, after trauma and burn, upon ventilation or in immuno-compromised patients. Many P. aeruginosa and S. aureus strains are resi...