A5040394315- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Glycogen Storage Diseases and Myoclonus
- Molecular Communication and Nanonetworks
- Pain Mechanisms and Treatments
- Photoreceptor and optogenetics research
- Ion Channels and Receptors
- Parkinson's Disease Mechanisms and Treatments
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Biotin and Related Studies
- Pharmacological Effects of Natural Compounds
- Botulinum Toxin and Related Neurological Disorders
- Retinal Development and Disorders
- Trypanosoma species research and implications
- Nerve injury and regeneration
- Photosynthetic Processes and Mechanisms
- Carbohydrate Chemistry and Synthesis
- Autophagy in Disease and Therapy
Universitätsklinikum Würzburg
2023-2025
University of Würzburg
2022-2023
Max Planck Institute of Biophysics
2021
Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation globotriaosylceramide. To study underlying pathomechanism Fabry-associated neuropathy, we generated neuronal
Acral and triggerable pain is a hallmark of diseases involving small nerve fiber impairment, yet the underlying cellular mechanisms remain elusive. A key role attributed to pain-related proteins located within neuronal plasma membrane nociceptive neurons. To explore this, we employed human induced pluripotent stem cell-derived sensory-like neurons enriched their surface by biotinylation. Samples from three independent cell differentiations were analyzed via liquid chromatography tandem mass...
Fabry disease (FD) is an X-linked genetic disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and intracellular globotriaosylceramide (Gb3) accumulation. To study FD-associated pathomechanisms, we generated isogenic control induced pluripotent stem cell (iPSC) line (IsoFD-1) from a patient-derived FD-iPSC (FD-1) carrying c.1069C>T mutation. Using CRISPR/Cas9 gene correction, restored wild-type sequence, confirmed Sanger sequencing absence of Gb3 deposits....
Fabry disease (FD) is a lysosomal storage disorder of X-linked inheritance. Mutations in the α-galactosidase A gene lead to cellular globotriaosylceramide (Gb3) depositions and triggerable acral burning pain both sexes as an early FD symptom unknown pathophysiology. We aimed at elucidating link between skin cells nociceptor sensitization contributing sex-associated manner. used cultured keratinocytes fibroblasts 27 adult patients 20 healthy controls. Epidermal dermal were immunoreacted...
Fabry disease (FD) is an X-linked multiorgan disorder caused by variants in the alpha-galactosidase A gene (GLA). Depending on variant, phenotypes range from benign to life-threatening. More than 1000 GLA are known, but a link between genotype and phenotype FD has not yet been established for all. p.A143T, p.D313Y, p.S126G frequent examples of unknown significance (VUS). We have investigated potential pathogenicity these VUS combining clinical data with obtained human cellular vitro systems....
Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with characteristic pain phenotype. Impaired GLA production or function leads to accumulation cell membrane compound globotriaosylceramide (Gb3) in neurons dorsal root ganglia (DRG) FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue knockout (KO) mouse model FD, we address question how Gb3 may...
Abstract The new class of microbial rhodopsins, called xenorhodopsins (XeRs), [1] extends the versatility this family by inward H + pumps. [2–4] These pumps are an alternative optogenetic tool to light‐gated ion channels (e.g. ChR1,2), because activation electrically excitable cells XeRs is independent from surrounding physiological conditions. In work we functionally and spectroscopically characterized XeR Nanosalina ( Ns XeR). photodynamic behavior was investigated on ps s time scale...
Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency caused variants in the gene GLA. Variants of unknown significance (VUS) are frequently found GLA and challenge clinical management. Here, we investigated 49-year old man with cryptogenic lacunar cerebral stroke chance finding VUS S126G, who was sent to our center for diagnosis initiation costly life-long FD-specific...
Abstract Acral burning pain triggered by fever, thermal hyposensitivity, and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation globotriaosylceramide (Gb3). To study underlying pathomechanism Fabry-associated neuropathy, we generated neuronal vitro disease model using patient-derived induced...
Human dermal fibroblasts (HDF) were obtained by skin punch biopsy from a 51-year old man with suspected Fabry disease (FD), carrying the hemizygous c.376A > G variant in α-galactosidase A gene (GLA). Cultured HDF reprogrammed to induced pluripotent stem cells (iPSC) using non-modified RNA-based transfection protocol. GLA-S126G-iPSC exhibit typical embryonic cell-like morphology, normal karyotype, expression of all tested pluripotency markers, and three germ layer differentiation potential....
Abstract Die neue Klasse der mikrobiellen Rhodopsine, genannt Xenorhodopine (XeR), [1] besitzen die besondere Eigenschaft des einwärtsgerichteten H + ‐Pumpens. [2–4] Diese Pumpen stellen eine Alternative zu den in Optogenetik etablierten Ionenkanäle ( z. B . ChR1,2) dar, denn Aktivierung von elektrisch anregbaren Zellen mit XeR ist unabhängig physiologischen Bedingungen ihrer Umgebung. In dieser Arbeit haben wir aus Nanosalina Ns XeR) funktionell und spektroskopisch charakterisiert. Das...