Flora M. Vaccarino
A5020168218- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Neuroscience and Neuropharmacology Research
- Obsessive-Compulsive Spectrum Disorders
- Neonatal and fetal brain pathology
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Genomics and Rare Diseases
- Fibroblast Growth Factor Research
- Neonatal Respiratory Health Research
- Autism Spectrum Disorder Research
- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- MicroRNA in disease regulation
- RNA Research and Splicing
- Renal and related cancers
- Ion channel regulation and function
- Anesthesia and Neurotoxicity Research
- Genetic Associations and Epidemiology
- Axon Guidance and Neuronal Signaling
Yale University
2016-2025
Kavli Institute for Theoretical Sciences
2023
Yale Cancer Center
2023
University of New Haven
2023
University at Buffalo, State University of New York
2020
Massachusetts General Hospital
2005-2020
University of Siena
2018
Institute of Medicinal Plant Development
2018
Medical Genetics Center
2018
Child Development Center
2000-2017
Genes overlap across psychiatric disease Many genome-wide studies have examined genes associated with a range of neuropsychiatric disorders. However, the degree to which genetic underpinnings these diseases differ or is unknown. Gandal et al. performed meta-analyses transcriptomic covering five major disorders and compared cases controls identify coexpressed gene modules. From this, they found that some share global expression patterns. This in polygenic traits may allow for better diagnosis...
Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterized by motor and vocal tics. Imaging studies found alterations in caudate (Cd) putamen volumes. To investigate possible cell populations, postmortem basal ganglia tissue from individuals with TS normal controls was analyzed using unbiased stereological techniques. A markedly higher total neuron number the globus pallidus pars interna (GPi) of TS. In contrast, lower density observed externa Cd. An increased proportion...
Human induced pluripotent stem cells (hiPSCs) are emerging as a tool for understanding human brain development at cellular, molecular, and genomic levels. Here we show that hiPSCs grown in suspension the presence of rostral neuralizing factors can generate 3D structures containing polarized radial glia, intermediate progenitors, spectrum layer-specific cortical neurons reminiscent their organization vivo. The hiPSC-derived multilayered express gene expression profile typical embryonic...
Abstract Corticobasal ganglia neuronal ensembles bring automatic motor skills into voluntary control and integrate them ongoing behavior. A 5% decrease in caudate (Cd) nucleus volume is the most consistent structural finding brain of patients with Tourette syndrome (TS), but cellular abnormalities that underlie this are unclear. In study density different types interneurons medium spiny neurons (MSNs) striatum was assessed postmortem brains 5 TS subjects as compared normal controls (NC) by...
Little is known about regionally specific signals that control the number of neuronal progenitor cells in vivo . We have previously shown germline mutation basic fibroblast growth factor (Fgf2) gene results a reduction cortical neurons adult. show here Fgf2 expressed pseudostratified ventricular epithelium (PVE) dorsoventral gradient and its receptor, Fgfr-1, are downregulated by mid to late stages neurogenesis. In knockout mice, volume cell dorsal PVE (the cerebral anlage) substantially...
The lifelong addition of neurons to the hippocampus is a remarkable form structural plasticity, yet molecular controls over proliferation, neuronal fate determination, survival, and maturation are poorly understood. Expression Notch1 was found change dynamically depending on differentiation state neural precursor cells. Through use inducible gain- loss-of-function mice we show that this membrane receptor essential these distinct processes. We in vivo activated overexpression induces whereas...
Genes implicated in neuropsychiatric disorders are active human fetal brain, yet difficult to study a longitudinal fashion. We demonstrate that organoids from pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially genes and enhancers, with greatest changes occurring at transition stem progenitors. Networks of converging gene enhancer modules were assembled into six four global patterns...
Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes single cells from forebrains three fetuses (15 to 21 weeks postconception) using clonal cell populations. detected 200 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found cancer genomes, indicating a role background mutagenesis cancer. SNVs with frequency >2% were also present spleen, revealing pregastrulation origin. reconstructed lineages for first five...
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays primary human cells from mid-gestation cortex cerebral organoids, we interrogated the cis-regulatory activity 102,767 open chromatin regions, including thousands sequences with cell type-specific accessibility variants associated brain regulation. In cells, identified 46,802 active enhancer 164 that alter activity. Activity was comparable...
In primary cultures of cerebellar granule cells, protein kinase C (PKC) translocation and activation can be triggered by the stimulation excitatory amino acid neurotransmitter receptors. Glutamate evokes a dose-related 4-beta-[3H]phorbol 12,13-dibutyrate ([3H]-P(BtO)2) binding sites from cytosol to neuronal membrane stimulates incorporation 32P into number proteins, particularly bands in range 80, 50, 40 kDa. The glutamate-evoked PKC is Mg2+ sensitive, prevented 2-amino-5-phosphonovalerate...
To identify the fates that astroglial cells can attain in postnatal brain, we generated mice carrying an inducible Cre recombinase (Cre-ER T2 ) controlled by human GFAP promoter ( hGFAP ). In GCE (hGFAP-Cre-ER transgene, OHT (4-hydroxy-tamoxifen) injections induced recombination at day 5 and allowed us to permanently tag these with reporter genes. Three days after recombination, reporter-tagged were quiescent expressed stem cell marker LeX subventricular zone (SVZ) dentate gyrus (DG). After...
Cells within the subventricular zone (SVZ) express basic Fgf <i>(Fgf2)</i> and receptor proteins. We show that absence of <i>Fgf2</i> gene products reduces by 50% dividing progenitor population anterior SVZ (SVZa) without changing their cell cycle time. Every 2–3 cycles SVZa population, 30,000 newly generated neurons capable long-term survival are added to glomerular layer olfactory bulb. knockout mice have smaller bulbs due decreased output these cells into bulbs. A...
Previous studies have shown that oligodendroglial progenitor cells (OPCs) can give rise to neurons in vitro and perinatal cerebral cortex vivo . We now report OPCs adult murine piriform express low levels of doublecortin, a marker for migratory immature neurons. Additionally, these Sox2, neural stem cell marker, Pax6, transcription factor characteristic progenitors cortical glutamatergic Genetic fate-mapping by means an inducible Cre–LoxP recombination system proved differentiate into...