A5073858666- Cell death mechanisms and regulation
- Mitochondrial Function and Pathology
- Glioma Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Phagocytosis and Immune Regulation
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Circular RNAs in diseases
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Anesthesia and Neurotoxicity Research
- Alzheimer's disease research and treatments
- Inflammasome and immune disorders
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Parkinson's Disease Mechanisms and Treatments
University of North Carolina at Chapel Hill
2016-2025
Institute of Neurobiology
2022-2024
Icahn School of Medicine at Mount Sinai
2023
Emory University
2023
Communities In Schools of Orange County
2012-2023
University of North Carolina Health Care
2016-2022
UNC Lineberger Comprehensive Cancer Center
2012-2015
University of Illinois Urbana-Champaign
2014
Stanford University
2014
Segeberger Kliniken
2013
Programmed cell death (apoptosis) is a normal process in the developing nervous system. Recent data suggest that certain features seen of programmed may be favored versus adult brain response to different injuries. In well characterized model neonatal hypoxia-ischemia, we demonstrate marked but delayed which there prominent DNA laddering, TUNEL-labeling, and nuclei with condensed chromatin. Caspase activation, required many cases apoptotic death, also followed time course after...
Dissociated cerebellar granule cells maintained in medium containing 25 mM potassium undergo an apoptotic death when switched to with 5 potassium. Granule from mice which Bax, a proapoptotic Bcl-2 family member, had been deleted, did not apoptosis potassium, yet excitotoxic cell response stimulation 30 or 100 μM NMDA. Within 2 h after switching K+, both wild-type and Bax-deficient decreased glucose uptake <20% of control. Protein synthesis also rapidly 50% control within 12 Both Bax...
Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between makes it challenging to replicate key findings integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC deeply characterized their genetic properties using whole genome sequencing, genomic stability upon CRISPR-Cas9-based gene editing, including differentiation commonly used types. These studies...
Members of the BCL-2 family proteins either promote or repress programmed cell death. Here we report that neonatal sympathetic neurons undergoing apoptosis after nerve growth factor (NGF) deprivation exhibited a protein synthesis-dependent, caspase-independent subcellular redistribution BAX from cytosol to mitochondria, followed by loss mitochondrial cytochrome c and Treatment with elevated concentrations neuroprotectants KCl cAMP at time prevented translocation release. However,...
Sympathetic neurons undergo programmed cell death (PCD) when deprived of NGF. We used an inhibitor to examine the function interleukin-1 beta-converting enzyme (ICE) family proteases during sympathetic neuronal and assess metabolic genetic status saved by such inhibition. Bocaspartyl(OMe)-fluoromethylketone (BAF), a cell-permeable ICE cysteine proteases, inhibited CPP32 (IC50 approximately 4 microM) in vitro blocked Fas-mediated apoptosis thymocytes (EC50 10 microM). At similar...
The execution of apoptosis is critical for proper development the nervous system. However, it equally important that neurons strictly inhibit after to ensure their survival throughout lifetime organism. Here we show a microRNA, miR-29b, markedly induced with neuronal maturation and functions as novel inhibitor apoptosis. prosurvival function miR-29b mediated by targeting genes in proapoptotic BH3-only family. Our results identify unique strategy evolved maturing uses single microRNA...
The 5' ends of eukaryotic mRNAs are blocked by a cap structure, m7GpppX (where X is any nucleotide). interaction the structure with cap-binding protein complex required for efficient ribosome binding to mRNA. In Saccharomyces cerevisiae, heterodimer composed two subunits molecular masses 24 (eIF-4E, CDC33) and 150 (p150) kDa. p150 presumed be yeast homolog p220 component mammalian eIF-4F. this report, we describe isolation gene TIF4631, which encodes p150, closely related gene, TIF4632....
Significance Protein aggregation is a hallmark of neurodegenerative disease and hypothesized to cause neuron death. Despite extensive study disease-associated aggregating proteins, mechanisms death remain mystery, no cures or effective treatments yet exist. Here, we demonstrate the toxicity small aggregate Cu,Zn superoxide dismutase (SOD1) protein, associated with amyotrophic lateral sclerosis (ALS). We present an experimentally verified structural model this toxic species show that SOD1...
Nerve growth factor (NGF) deprivation induces a Bax-dependent, caspase-dependent programmed cell death in sympathetic neurons. We examined whether the release of cytochrome c was accompanied by loss mitochondrial membrane potential during neuronal death. NGF- deprived, caspase inhibitor–treated mouse neurons maintained poten-tial for 25–30 h after releasing c. deprived became committed to die, as measured inability cells be rescued NGF readdition, at time release. In presence inhibitor,...
In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release activate caspases. Thus, although cells die rapidly with cytosolic alone, neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor protein (XIAP) as essential postcytochrome regulator caspase activation these neurons. contrast wild-type that injection c,...
Ribosomal protein L1 from Saccharomyces cerevisiae binds 5S rRNA and can be released intact 60S ribosomal subunits as an L1-5S ribonucleoprotein (RNP) particle. To understand the nature of interaction between to assess role in ribosome assembly function, we cloned RPL1 gene encoding L1. We have shown that is essential single-copy gene. A conditional null mutant which only copy under control repressible GAL1 promoter was constructed. Depletion causes instability newly synthesized vivo. Cells...
While aerobic glycolysis is linked to unconstrained proliferation in cancer, less known about its physiological role. Why this metabolic program that promotes tumor growth preserved the genome has thus been unresolved. We tested hypothesis derives from developmental processes regulate rapid proliferation.