A5062470823- RNA Research and Splicing
- RNA modifications and cancer
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- PARP inhibition in cancer therapy
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Chromosomal and Genetic Variations
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Intracranial Aneurysms: Treatment and Complications
- Reproductive Biology and Fertility
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- Advanced biosensing and bioanalysis techniques
- Immunotherapy and Immune Responses
- DNA Repair Mechanisms
- Sperm and Testicular Function
University of Edinburgh
2024-2025
Max Planck Institute for Brain Research
2018-2022
University of California San Diego Medical Center
2020
Emory University
2013-2018
National Institutes of Health
2017
Institute of Cell Biology
2016
AID Atlanta
2013
The cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark the amyotrophic lateral sclerosis frontotemporal dementia disease spectrum (ALS/FTD). However, composition aggregates their contribution to process remain unknown. Here we used proximity-dependent biotin identification (BioID) interrogate interactome detergent-insoluble TDP-43 found them enriched for components nuclear pore complex nucleocytoplasmic transport...
Local translation in presynaptic terminals Proteins carry out most of the functions cells, including neurons, which are one morphologically complex cell types body. This poses challenges for how proteins can be supplied to remote regions where connections (synapses) made with other neurons. One solution neuron protein-supply problem involves local synthesis from messenger RNA (mRNA) molecules located at or near synapses. Hafner et al. used sequencing methods and superresolution microscopy...
Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It caused by reduced levels of the survival neuron (SMN) protein, which plays an essential role in biogenesis spliceosomal small nuclear ribonucleoproteins all tissues. The etiology specific defects circuitry SMA still unclear, but SMN has also been implicated mediating axonal localization mRNA-protein complexes, may contribute to degeneration observed SMA. Here, we report that deficiency...
Significance Local protein synthesis is important for neuronal function and synaptic plasticity. Thousands of mRNAs are found in axons dendrites, it believed that regulating their dynamic transport distribution a key determinant where when proteins made. In this work we quantitatively assessed the three synaptically localized live cultured neurons without exogenous stimulation following induction two distinct forms Coupling observations mRNA dynamics with imaging endogenous dynamics,...
Spinal muscular atrophy (SMA) is a lethal neurodegenerative disease specifically affecting spinal motor neurons. SMA caused by the homozygous deletion or mutation of survival neuron 1 (SMN1) gene. The SMN protein plays an essential role in assembly spliceosomal ribonucleoproteins. However, it still unclear how low levels ubiquitously expressed lead to selective degeneration An additional for regulation axonal transport mRNA-binding proteins (mRBPs) and their target mRNAs has been proposed....
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival (SMN) protein. SMN part multiprotein complex that facilitates assembly spliceosomal small nuclear ribonucleoproteins (snRNPs). has also been found to associate with mRNA-binding proteins, but nature this association was unknown. Here, we have employed combination biochemical and advanced imaging methods demonstrate promotes molecular interaction between IMP1 protein 3′ UTR zipcode region β-actin...
We examined the feedback between major protein degradation pathway, ubiquitin-proteasome system (UPS), and synthesis in rat mouse neurons. When was inhibited, we observed a coordinate dramatic reduction nascent neuronal cell bodies dendrites. The mechanism for translation inhibition involved phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated inhibitor (HRI). Under basal conditions, expression HRI is barely detectable. Following proteasome inhibition, levels...
DREF was first characterized for its role in the regulation of transcription genes encoding proteins involved DNA replication and found to interact with sequences similar recognition motif BEAF-32 insulator protein. Insulators are DNA-protein complexes that mediate intra- inter-chromosome interactions. Several DNA-binding have been described Drosophila, including BEAF-32, dCTCF Su(Hw). Here we find co-localize at same genomic sites, but their enrichment shows an inverse correlation....
Posttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 variant CENP-A, few have been reported, their functions remain largely unexplored. In this multidisciplinary report, we utilize silico computational vivo approaches to dissect lysine 124 human which was previously reported be acetylated advance replication. Computational modeling...
The proper regulation of spermatogenesis is crucial to ensure the continued production sperm and fertility. Here, we investigated function H3K4me2 demethylase KDM1A/LSD1 during in developing adult mice. Conditional deletion Kdm1a testis just prior birth leads fewer spermatogonia germ cell loss before 3 weeks age. These results demonstrate that KDM1A required for spermatogonial differentiation, as well survival, testis. In addition, inducible abnormal accumulation meiotic spermatocytes,...
Fragile X syndrome (FXS), a commonly inherited form of autism and intellectual disability, is associated with emotional symptoms that implicate dysfunction the amygdala. However, current understanding pathogenesis disease based primarily on studies in hippocampus neocortex, where FXS defects have been corrected by inhibiting group I metabotropic glutamate receptors (mGluRs). Here, we observe activation, rather than inhibition, mGluRs basolateral amygdala reverses impairments rat model FXS....
Herein, we present a new class of Q-dye molecular beacons (MBs) that can be locally activated with visible light in hippocampal neurons. Our novel architecture increases the available monitoring time for neuronal mRNA from several minutes to 14 hours, since lower light-sampling rate is required tracking.
Abstract Decades of work have demonstrated that mRNAs are localized and translated within neuronal dendrites axons to provide proteins for remodeling maintaining growth cones or synapses. It remains unknown, however, whether specific forms plasticity differentially regulate the dynamics translation individual mRNA species. To address these issues, we targeted three synaptically-localized mRNAs, CamkIIa , Beta actin Psd95 used molecular beacons track endogenous movements reporters Crispr-Cas9...
Abstract There is ample evidence for localized mRNAs and protein synthesis in neuronal dendrites, however, demonstrations of these processes presynaptic terminals are limited. We used expansion microscopy to resolve pre- postsynaptic compartments brain slices. Most the hippocampus forebrain contained mRNA ribosomes. sorted fluorescently labeled synaptosomes from mouse then sequenced hundreds species present within excitatory boutons. After brief metabolic labeling, more them 30% all...