A5042911910- Signaling Pathways in Disease
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Ion channel regulation and function
- Cardiac Fibrosis and Remodeling
- Planarian Biology and Electrostimulation
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- Cancer-related gene regulation
- Neurogenesis and neuroplasticity mechanisms
- Cardiomyopathy and Myosin Studies
- Alzheimer's disease research and treatments
- Cardiac electrophysiology and arrhythmias
- Cardiac Ischemia and Reperfusion
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- Animal Genetics and Reproduction
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- HIV/AIDS drug development and treatment
- Tissue Engineering and Regenerative Medicine
- Biochemical and Molecular Research
- Histone Deacetylase Inhibitors Research
ShanghaiTech University
2017-2024
Technische Universität Dresden
2009-2024
University Hospital Carl Gustav Carus
2017
Max Planck Institute for Developmental Biology
2004-2009
The University of Texas Southwestern Medical Center
1998-2006
University of California, Los Angeles
2006
Harvard University
2004
Tufts University
2004
Southwestern Medical Center
2003
University of Würzburg
2003
Environmental stresses converge on the mitochondria that can trigger or inhibit cell death. Excitable, postmitotic cells, in response to sublethal noxious stress, engage mechanisms afford protection from subsequent insults. We show reoxygenation after prolonged hypoxia reduces reactive oxygen species (ROS) threshold for mitochondrial permeability transition (MPT) cardiomyocytes and survival is steeply negatively correlated with fraction of depolarized mitochondria. Cell exhibits a memory...
The adult myocardium responds to a variety of pathologic stimuli by hypertrophic growth that frequently progresses heart failure. calcium/calmodulin-dependent protein phosphatase calcineurin is potent transducer stimuli. Calcineurin dephosphorylates members the nuclear factor activated T cell (NFAT) family transcription factors, which results in their translocation nucleus and activation calcium-dependent genes. Glycogen synthase kinase-3 (GSK-3) phosphorylates NFAT proteins antagonizes...
ABSTRACT We have produced null mutant mouse embryonic stem cells for the cell adhesion molecule E-cadherin. Such E-cadherin−/− ES are defective in aggregation; this defect can be corrected by transfection with cDNA either E-cadherin or N-cadherin driven a constitutive promoter. The presence (or absence) of regulates expression transcription factor T-brachyury, indicating that cadherins play role linking surface receptors and gene expression. Comparative analysis parental genetically altered...
Signaling events controlled by calcineurin promote cardiac hypertrophy, but the degree to which such pathways are required transduce effects of various hypertrophic stimuli remains uncertain. In particular, administration immunosuppressive drugs that inhibit has inconsistent in blocking hypertrophy animal models. As an alternative approach inhibiting hearts intact animals, transgenic mice were engineered overexpress a human cDNA encoding calcineurin-binding protein, myocyte-enriched...
β-Adrenergic receptor (βAR) signaling, which elevates intracellular cAMP and enhances cardiac contractility, is severely impaired in the failing heart. Protein kinase A (PKA) activated by cAMP, but long-term physiological effect of PKA activation on function unclear. To investigate consequences chronic absence upstream events associated with βAR we generated transgenic mice that expressed catalytic subunit These developed dilated cardiomyopathy reduced arrhythmias, susceptibility to sudden...
Postnatal cardiac myocytes respond to stress signals by hypertrophic growth and activation of a fetal gene program. Recently, we showed that class II histone deacetylases (HDACs) suppress hypertrophy, mice lacking the HDAC, HDAC9, are sensitized signals. To further define roles HDACs in analyzed effects HDAC inhibitors on responsiveness primary cardiomyocytes agonists. Paradoxically, imposed dose-dependent blockade hypertrophy activation. We conclude distinct play positive or negative...
The transcription factor NFAT5/TonEBP, a member of the NFAT/Rel family factors, has been implicated in diverse cellular responses, including response to osmotic stress, integrin-dependent cell migration, T activation, and Ras pathway Drosophila . To clarify vivo role NFAT5, we generated NFAT5-null mice. Homozygous mutants were genetically underrepresented after embryonic day 14.5. Surviving mice manifested progressive profound atrophy kidney medulla with impaired activation several...
In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly sarcomeres, and cellular enlargement. We show that signals stimulate the expression transcriptional activity myocardin, cardiac smooth muscle-specific coactivator serum factor (SRF). Consistent with role for myocardin as transducer forced in is sufficient substitute induce cardiomyocyte hypertrophy program. Conversely, dominant-negative mutant form...
The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although sequences structures of TEAD highly conserved, each isoform has unique physiological pathological functions. Therefore, development discovery subtype selective inhibitors for protein will provide important chemical probes TEAD-related function studies diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072)...
Environmental stresses converge on the mitochondria that can trigger or inhibit cell death. Excitable, postmitotic cells, in response to sublethal noxious stress, engage mechanisms afford protection from subsequent insults. We show reoxygenation after prolonged hypoxia reduces reactive oxygen species (ROS) threshold for mitochondrial permeability transition (MPT) cardiomyocytes and survival is steeply negatively correlated with fraction of depolarized mitochondria. Cell exhibits a memory...
Although beta-adrenergic receptor (AR) blockade therapy is beneficial in the treatment of heart failure, little known regarding transcriptional mechanisms underlying this salutary action.In present study, we screened mice overexpressing Gsalpha, beta1AR, beta2AR, or protein kinase A to test if a common genomic pathway exists different models with enhanced signaling. In differentially expressed genes were identified by mRNA profiling. addition well-known markers cardiac hypertrophy (atrial...
Abstract Microtubule-associated TAU protein is a pathological hallmark in Alzheimer’s disease (AD), where hyperphosphorylation of generates neurofibrillary tangles. To investigate the effects regenerative adult vertebrate brain system, we generated cre/lox-based transgenic model zebrafish that chronically expresses human P301L , which variant forms tangles mouse models and humans. Interestingly, found although chronic abundant expression starting from early embryonic development led to...
Canonical β-catenin-dependent Wnt signal transduction is important for several biological phenomena, such as cell fate determination, proliferation, stem maintenance and anterior-posterior axis formation. The hallmark of canonical signaling the translocation β-catenin into nucleus where it activates gene transcription. However, mechanisms regulating nuclear localization are poorly understood. We show that Simplet/Fam53B (Smp) required by positively localization. In zebrafish embryo, loss smp...
The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth adult zebrafish appendages. However, it remains unknown how this and its bioelectric is regulated to scale these anatomical structures. We show activation sufficient activate several genes that are part important development programs. provide vivo transplantation evidence gene transcription cell autonomous. also will induce expression different subsets tested developmental cultured...
Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy (HCM) that is characterized by hypertrophy, histopathology, contractile dysfunction, and sudden death. The signaling pathways involved the pathology of HCM have not been elucidated, an unresolved question whether blocking growth may be maladaptive or beneficial. To address these questions, a mouse model was crossed with antihypertrophic constitutive activated glycogen synthase kinase-3beta (caGSK-3beta). Active...