A5017948966- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related Molecular Pathways
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Axon Guidance and Neuronal Signaling
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Signaling Pathways in Disease
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Pluripotent Stem Cells Research
- Microtubule and mitosis dynamics
- Neurological disorders and treatments
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
Cancer Genetics (United States)
2016-2025
Center for Cancer Research
2016-2025
National Cancer Institute
2015-2024
National Institutes of Health
2015-2024
MRC Laboratory of Molecular Biology
2022
Frederick National Laboratory for Cancer Research
2007-2019
Cancer Institute (WIA)
2009-2019
Garvan Institute of Medical Research
2010
Walter and Eliza Hall Institute of Medical Research
2010
Eötvös Loránd University
2010
Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with recruitment factors damaged DNA. To help clarify physiological role H2AX, we targeted in mice. Although not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, immune deficient, mutant males infertile. These pleiotropic phenotypes chromosomal...
Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, role of endogenous BDNF development and function these not been established vivo because early postnatal lethality null mice. In present study, we use heterozygous +/− mice that have a normal life span show animals develop enhanced intermale aggressiveness hyperphagia accompanied by significant weight gain adulthood; behavioral abnormalities are known to...
Abstract Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic environmental factors. It known that exposure an enriched environment enhances number of newly generated neurons dentate gyrus. However, mechanisms which housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice brain‐derived neurotrophic factor (BDNF +/– ) lacking neurotrophin‐4 (NT‐4 –/– together with their wild‐type...
ABSTRACT The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of developing embryo. function these along axis embryo has generally interpreted in context positional specification homeotic transformation axial structures. way which are expressed during development axes, particularly limb, is less clear. In order provide a reference understanding role limb patterning, we isolated clones 23 development, characterized their expression patterns...
Transactivating response region DNA binding protein (TDP-43) is the major component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with inclusions. Two ALS-causing mutants (TDP-43(Q331K) TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon neuron death when expressed mice at levels a cell type-selective pattern similar endogenous TDP-43. Mutant...
A large number of intercellular signaling molecules have been identified that orchestrate female reproductive physiology. However, with the exception steroid hormone receptors, little information exists about transcriptional regulators mediate cellular responses to these signals. The transcription factor C/EBPβ ( C CAAT/ e nhancer- b inding p rotein β ) is expressed in ovaries and testes, as well many other tissues adult mice. Here we show mice carrying a targeted deletion gene exhibit...
B R Stanton, A S Perkins, L Tessarollo, D Sassoon, and F Parada Molecular Embryology Section, National Cancer Institute-Frederick Research Development Center, Maryland 21702-1201.
Cyclin-dependent kinase 1 (Cdk1) is an archetypical and a central regulator that drives cells through G2 phase mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the vivo functions Cdk1 not been fully explored mammals. Here we generated conditional-knockout mouse model to study vivo. Ablation leads arrest embryonic development around blastocyst stage. Interestingly, liver-specific deletion well tolerated, liver regeneration after partial hepatectomy impaired,...
Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some which are causally involved in tumorigenesis (drivers) others that have little functional impact (passengers). To help distinguish between these two classes we used transposon-based screen mice to identify candidate genes for CRC. Mice harboring mutagenic Sleeping Beauty (SB) transposons were crossed with expressing SB transposase gastrointestinal tract epithelium. Most the offspring developed...
Abstract Since the start of COVID-19 pandemic, SARS-CoV-2 has caused millions deaths worldwide. Although a number vaccines have been deployed, continual evolution receptor-binding domain (RBD) virus challenged their efficacy. In particular, emerging variants B.1.1.7, B.1.351 and P.1 (first detected in UK, South Africa Brazil, respectively) compromised efficacy sera from patients who recovered immunotherapies that received emergency use authorization 1–3 . One potential alternative to avert...
Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine levels, both wild-type and ALS-causing frontotemporal dementia (FTD)-causing mutations complement essential function(s) FUS. Replacement with mutant, but not wild-type, causes stress-mediated induction chaperones, decreased expression ion channels transporters for synaptic function, reduced activity without loss nuclear or its cytoplasmic aggregation. Most...
Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the adult brain and can prevent severe loss of cortical 5-HT axons caused by neurotoxin p -chloroamphetamine (PCA). However, it not been determined whether BDNF promotes survival during PCA-insult or facilitates their regenerative sprouting after injury. We show here that fails to protect most from PCA-induced degeneration. Instead, chronic infusions markedly stimulate both intact PCA-lesioned...
Recent studies in Saccharomyces cerevisiae suggest that the delivery of copper to Cu/Zn superoxide dismutase (SOD1) is mediated by a cytosolic protein termed chaperone for (CCS). To determine role CCS mammalian homeostasis, we generated mice with targeted disruption alleles ( −/− mice). Although are viable and possess normal levels SOD1 protein, they reveal marked reductions activity when compared control littermates. Metabolic labeling 64 Cu demonstrated reduction direct result impaired...
The cytokine interferon (IFN)-γ regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. Recently, a family IFN-γ–induced genes has been identified that encode 48-kD GTP-binding proteins localize to endoplasmic reticulum cells. prototype this family, IGTP, shown be required for host defense against acute infections with protozoan parasite Toxoplasma gondii, but not normal bacterium Listeria monocytogenes murine...