A5084852985- Cancer, Lipids, and Metabolism
- Mitochondrial Function and Pathology
- Lung Cancer Research Studies
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Carcinogens and Genotoxicity Assessment
- Cancer, Hypoxia, and Metabolism
- Glutathione Transferases and Polymorphisms
- Genetic Neurodegenerative Diseases
- Sphingolipid Metabolism and Signaling
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Effects and risks of endocrine disrupting chemicals
- Protein Kinase Regulation and GTPase Signaling
- HIV/AIDS drug development and treatment
- Metabolomics and Mass Spectrometry Studies
- Heavy Metal Exposure and Toxicity
- Hereditary Neurological Disorders
TU Dortmund University
2009-2019
Leibniz Research Centre for Working Environment and Human Factors
2009-2019
University of Southampton
2012-2017
University of Auckland
2013
Newcastle University
2007-2012
Wellcome Centre for Mitochondrial Research
2008-2012
University Hospital Frankfurt
2012
Goethe University Frankfurt
2012
Leibniz Institute for Neurobiology
2012
Churchill Hospital
2010
Additional neurological features have recently been described in seven families transmitting pathogenic mutations OPA1, the most common cause of autosomal dominant optic atrophy. However, frequency these syndromal 'dominant atrophy plus' variants and extent involvement not established. In this large multi-centre study 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular complications are OPA1 disease, affect up to 20% all mutational carriers. Bilateral...
Mutations in nuclear genes involved mitochondrial DNA (mtDNA) maintenance cause a wide range of clinical phenotypes associated with the secondary accumulation multiple mtDNA deletions affected tissues. The majority families autosomal dominant progressive external ophthalmoplegia (PEO) harbour mutations encoding one three well-characterized proteins—polγ, Twinkle or Ant 1. Here we show that heterozygous mis-sense mutation OPA1 leads to skeletal muscle and mosaic defect cytochrome c oxidase...
Abstract Purpose: Although the central role of immune system for tumor prognosis is generally accepted, a single robust marker not yet available. Experimental Design: On basis receiver operating characteristic analyses, markers were identified from 60-gene B cell–derived metagene and analyzed in gene expression profiles 1,810 breast cancer; 1,056 non–small cell lung carcinoma (NSCLC); 513 colorectal; 426 ovarian cancer patients. Protein RNA levels examined paraffin-embedded tissue 330 The...
Sodium valproate (VPA) is widely used throughout the world to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy. VPA toxicity an uncommon but potentially fatal cause of idiosyncratic liver injury. Rare mutations in POLG, which codes for mitochondrial DNA polymerase γ (polγ), Alpers-Huttenlocher syndrome (AHS). AHS a neurometabolic disorder associated with increased risk developing hepatotoxicity. We therefore set out determine whether common genetic...
Metastasis from primary tumors remains a major problem for tumor therapy. In the search markers of metastasis and more effective therapies, metabolome is relevant because its importance to malignant phenotype metastatic capacity cells. Altered choline metabolism hallmark cancer. More specifically, decreased glycerophosphocholine (GPC) phosphocholine (PC) ratio was reported in breast, ovarian, prostate cancers. Improved strategies exploit this altered are therefore required. However, critical...
Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting accumulation multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)-deficient fibers skeletal muscle secondary to disorder mtDNA maintenance. Patients typically present with isolated extraocular involvement, little apparent evidence clinical heterogeneity documented other maintenance disorders, particular POLG-related disease.We...
We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for arrayed mass production highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, array impacts growth kinetics and can be tuned to produce ranging in diameter from 200 550 µm. diffusive limit competition media occurred with a pitch ≥1250 µm was used optimal array-based culture large, viable During...
<h3>Background</h3> Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological disc cupping and visual field defects. The <i>OPA1</i> gene encodes an inner mitochondrial membrane protein crucial for normal function, pathogenic mutations cause autosomal dominant atrophy specifically targeting cells. This raises distinct possibility that more subtle genetic variations in could alter risk developing glaucoma....
Abstract Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), enzymes that catabolize products determine which downstream pathway is relevant for migration. Our results clearly showed influenced migration via signaling lipid lysophosphatidic acid (LPA), linking it...
Endothelial lipase (LIPG) is a cell surface associated that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed breast cancer and support proliferation, tumourigenicity metastasis. Here we show severe oxidative stress leading AMPK activation triggers upregulation, resulting intracellular lipid droplet accumulation cells, which supports survival. Neutralizing abrogated upregulation the...
Mitochondrial DNA depletion syndrome, a frequent cause of childhood (hepato)encephalomyopathies, is defined as reduction mitochondrial copy number related to nuclear DNA. It was previously shown that mtDNA can be prevented by dAMP/dGMP supplementation in deoxyguanosine kinase-deficient fibroblasts. We investigated myotubes patients diagnosed with carrying pathogenic mutations DGUOK, POLG1 (Alpers syndrome) and TYMP . Differentiating all controls were supplemented different doses or...
<h3>Background:</h3> The <i>POLG1</i> gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial replication and repair. Mutations in have been linked to a spectrum clinical phenotypes, may account up 25% all adult presentations disease. <h3>Methods results:</h3> We present 14 patients, with characteristic features disease including progressive external ophthalmoplegia (PEO) Alpers–Huttenlocher syndrome laboratory findings indicative dysfunction, cytochrome...
Recently, epithelial to mesenchymal transition (EMT) has been shown represent a feature of dedifferentiating hepatocytes in vitro. Three-dimensional soft collagen gels can antagonize but not completely abolish this effect. Hormonal additives culture media are known maintain differentiated hepatocyte functions. Therefore, we studied whether insulin and dexamethasone EMT cultured hepatocytes. Both hormones antagonized abolished certain morphological features EMT. Dexamethasone acquisition...
<h3>Background</h3> Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present diagnostic challenge. <h3>Objective</h3> To determine the cause of CMT type 2 3 siblings. <h3>Design</h3> Case report. <h3>Setting</h3> Academic research. <h3>Participants</h3> Three siblings who subsequently developed profound cerebellar ataxia. <h3>Main Outcome Measures</h3> Muscle biopsy specimen genetic...
The instability of the mitochondrial genome in individuals harboring pathogenic mutations catalytic subunit DNA (mtDNA) polymerase gamma (POLG) is well recognized, but underlying molecular mechanisms remain to be elucidated. In 5 pediatric patients with severe myoclonic epilepsy and valproic acid-induced liver failure, we identified 1 novel 4 previously described linker region this enzyme. Although muscle biopsies these showed unremarkable histologic features, postmortem tissue available...
Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed association B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival untreated node-negative cancer patients.IGKC expression was evaluated by immunostaining a cohort 335 patients with median follow-up 152 months. The significance IGKC for disease-free (DFS) cancer-specific overall (OS) Kaplan-Meier analysis well univariate multivariate Cox adjusted age at diagnosis, pT...
Endometrial carcinoma differential 3 (EDI3) was the first member of glycerophosphodiesterase (GDE) protein family shown to be associated with cancer. Our initial work demonstrated that endometrial and ovarian cancer patients primary tumors overexpressing EDI3 had a higher risk developing metastasis decreased survival. Further analysis indicated cleaves glycerophosphocholine choline glycerol-3-phosphate, increases levels active PKC, enhances migratory activity tumor cells. Despite these...
We analyzed all cases of community-onset Staphylococcus aureus skin and soft tissue infection in children presenting to our hospital between 2007 2010. A total 1860 were included. There was significant sociodemographic disparity, with the incidence disproportionately higher Maori Pacific Island residing deprived areas.
ATP-binding cassette 50 (ABC50; also known as ABCF1) binds to eukaryotic initiation factor 2 (eIF2) and is required for efficient translation initiation. An essential step of this process accurate recognition selection the codon. It widely accepted that presence movement eIF1, eIF1A eIF5 are key factors in modulating stringency start-site selection, which normally requires an AUG codon appropriate sequence context. In present study, we show expression ABC50 mutants, cannot hydrolyse ATP,...