Uwe Kornak
A5006161077- Connective tissue disorders research
- Bone Metabolism and Diseases
- Bone health and treatments
- Dermatological and Skeletal Disorders
- Ubiquitin and proteasome pathways
- Bone and Dental Protein Studies
- Genomics and Rare Diseases
- Trace Elements in Health
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Nuclear Structure and Function
- Genomic variations and chromosomal abnormalities
- Skin and Cellular Biology Research
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Genetic factors in colorectal cancer
- Ion channel regulation and function
- ATP Synthase and ATPases Research
- Erythrocyte Function and Pathophysiology
- Digestive system and related health
- Congenital heart defects research
- Bone health and osteoporosis research
- Cellular Mechanics and Interactions
- Alkaline Phosphatase Research Studies
- Cell death mechanisms and regulation
Universitätsmedizin Göttingen
2020-2025
Endokrinologikum
2025
Humboldt-Universität zu Berlin
2006-2024
Charité - Universitätsmedizin Berlin
2015-2024
Max Planck Institute for Molecular Genetics
2015-2024
Freie Universität Berlin
2010-2024
German Medical Association
2024
Cincinnati Children's Hospital Medical Center
2024
National Hospital for Neurology and Neurosurgery
2024
University College London
2024
Chloride channels play important roles in the plasma membrane and intracellular organelles. Mice deficient for ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis retinal degeneration. Although osteoclasts are present normal numbers, they fail to resorb bone because cannot acidify extracellular resorption lacuna. resides late endosomal lysosomal compartments. In osteoclasts, it is highly ruffled membrane, formed by fusion of H(+)-ATPase-containing vesicles, that secretes...
Patients with genetic disease of unknown causes can be rapidly diagnosed by bioinformatic analysis disease-associated DNA sequences and phenotype.
Although the gene defects for several mouse mutants with severe osteopetrosis are known, genes underlying human infantile malignant recessive remain elusive. Osteopetrosis is thought to be caused by a defect in osteoclast function. These cells degrade bone material tightly sealed extracellular compartment that acidified vacuolar (V)-type H+-ATPase. Genes encoding components of acidification machinery candidate osteopetrosis. In five ten patients osteopetrosis, we now demonstrate different...
During lysosomal acidification, proton-pump currents are thought to be shunted by a chloride ion (Cl-) channel, tentatively identified as ClC-7. Surprisingly, recent data suggest that ClC-7 instead mediates Cl-/proton (H+) exchange. We generated mice carrying point mutation converting into an uncoupled (unc) Cl- conductor. Despite maintaining conductance and normal pH, these Clcn7(unc/unc) showed storage disease like lacking However, their osteopetrosis was milder, they lacked coat color...
Osteoporosis is one of the most common degenerative diseases. It characterized by reduced bone mineral density (BMD) with an increased risk for fractures. There a substantial genetic contribution to BMD, although factors involved in pathogenesis human osteoporosis are largely unknown. Mice targeted deletion either cannabinoid receptor type 1 (Cnr1) or 2 (Cnr2) gene show alteration mass, and pharmacological modification both receptors can regulate osteoclast activity BMD. We therefore...
Mammalian CLC proteins function as Cl(-) channels or electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane intracellular vesicles. We now show that ClC-6 protein is almost exclusively expressed neurons of central peripheral nervous systems, with a particularly high expression dorsal root ganglia. colocalized markers for late endosomes neuronal cell bodies. The disruption mice reduced their pain sensitivity caused moderate behavioral abnormalities. Neuronal tissues showed...
Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay redundant, inelastic skin, is caused by mutations in the a2 subunit vesicular ATPase H+-pump (ATP6V0A2). The goal this study was to define disease mechanisms that lead connective tissue lesions ARCL2. In new cohort 17 patients, DNA sequencing ATP6V0A2 detected either homozygous or compound heterozygous mutations. Considerable allelic phenotypic heterogeneity observed, with missense mutation moderately...
Abstract During vertebrate skeletal development, osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix. Anoctamin6/Tmem16F (Ano6) belongs to conserved family transmembrane proteins with chloride channel properties. In addition, Ano6 has been linked phosphatidylserine (PS) scrambling plasma membrane. skeletogenesis, mRNA is expressed differentiating and mature osteoblasts. Deletion mice results reduced skeleton size deformities....
Many neurodegenerative disorders present with sensory loss. In the group of hereditary and autonomic neuropathies loss nociception is one disease hallmarks. To determine underlying factors neurodegeneration we performed whole-exome sequencing in affected individuals disorder. a family neuropathy pain perception destruction pedal skeleton report missense mutation highly conserved amino acid residue atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same (p.Tyr192Cys) was...
PurposePhenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible bioinformatics workflows after encoding into clinical terms by expert dysmorphologists.MethodsHere, we introduce an approach driven artificial intelligence that uses portrait photographs exome data. We measured value added computer-assisted image analysis to diagnostic yield on a cohort consisting 679 individuals with 105 different monogenic disorders. For each case in...
Multipotent stromal cells are considered attractive sources for cell therapy and tissue engineering. Despite numerous experimental clinical studies, broad application of therapeutics is not yet emerging. A major challenge the functional diversity available sources. Here, we investigated regenerative potential clinically relevant human from bone marrow (BMSCs), white adipose tissue, umbilical cord compared with mature chondrocytes skin fibroblasts in vitro vivo. Although all types could...
Abstract Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, 3-year prospective study, we evaluated novel diagnostic concept based on multidisciplinary expertise in Germany. Here present the systematic investigation of phenotypic and molecular genetic data 1,577 patients who had undergone exome sequencing were partially analyzed next-generation phenotyping approaches....
Poly-alanine (Ala) tract expansions in transcription factors have been shown to be associated with human birth defects such as malformations of the brain, digits, and other structures. Expansions a poly-Ala from 15 22 (+7)–29 (+14) Ala Hoxd13, for example, result limb malformation synpolydactyly humans mice [synpolydactyly homolog (spdh)]. Here, we show that an increase repeat above certain length (22 Ala) is shift localization Hoxd13 nuclear cytoplasmic, where it forms large amorphous...
Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder primarily characterized by the formation of neurofibromas, café-au-lait spots and freckling. Skeletal abnormalities such as short stature or bowing/pseudarthrosis tibia are relatively common. To investigate role neurofibromin in skeletal development, we crossed Nf1flox mice with Prx1Cre to inactivate Nf1 undifferentiated mesenchymal cells developing limbs. Similar NF1 affected individuals, Nf1Prx1 show bowing diminished growth....