Caroline Dias
A5005173482- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Neurotransmitter Receptor Influence on Behavior
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Single-cell and spatial transcriptomics
- Adipose Tissue and Metabolism
- Genetic Neurodegenerative Diseases
- Genomics and Chromatin Dynamics
- Wnt/β-catenin signaling in development and cancer
- Prenatal Screening and Diagnostics
- Mitochondrial Function and Pathology
- Renal and related cancers
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
- Tryptophan and brain disorders
- Nuclear Receptors and Signaling
- PARP inhibition in cancer therapy
University of Colorado Anschutz Medical Campus
2023-2025
Harvard University
2019-2024
Boston Children's Hospital
2018-2024
University of Colorado System
2024
Howard Hughes Medical Institute
2020-2023
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2023
University of Colorado Denver
2023
Children's Hospital Colorado
2023
Icahn School of Medicine at Mount Sinai
2011-2019
Allen Institute for Brain Science
2012-2017
Abstract Background Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on brain, and recent work has demonstrated involvement chromatin modifications these alterations. However, all such studies to date have been restricted by their reliance microarray technologies that intrinsic limitations. Results We use next generation sequencing methods, RNA-seq ChIP-seq RNA polymerase II several histone methylation marks, obtain more complete...
Based on earlier gene expression and chromatin array data, we identified the protein, dishevelled (DVL)-2, as being regulated in nucleus accumbens (NAc), a key brain reward region, mouse social defeat model of depression. Here, validate these findings by showing that DVL2 mRNA protein levels are downregulated NAc mice susceptible to stress, effects not seen resilient mice. Other DVL isoforms, DVL1 DVL3, show similar patterns regulation. Downregulation was also demonstrated depressed humans...
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 schizophrenia, and 59 autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, had 20 60 detectable single-nucleotide mutations, but ~6% harbored hundreds mutations. Hypermutability was associated age damaging in genes implicated cancers and, some brains, reflected vivo clonal expansions. Somatic duplications, likely arising during development, were found ~5% normal...
Numerous studies have found that chronic cocaine increases dendritic spine density of medium spiny neurons in the nucleus accumbens (NAc). Here, we used single-cell microinjections and advanced 3D imaging analysis techniques to extend these findings several important ways: by assessing regulation spines core versus shell subregions NAc mouse, over a broad time course (4 h, 24 or 28 d) withdrawal from cocaine, with particular focus on proximal distal dendrites. Our data demonstrate...
Regulator of G protein signaling 4 (Rgs4) is a signal transduction that controls the function monoamine, opiate, muscarinic, and other protein-coupled receptors via interactions with Gα subunits. Rgs4 expressed in several brain regions involved mood, movement, cognition, addiction regulated by psychotropic drugs, stress, corticosteroids. In this study, we use genetic mouse models viral-mediated gene transfer to examine role actions antidepressant medications. We first analyzed human...
Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast methylation, role Arg (R) remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) its associated mark, asymmetric dimethylation R2 H3 (H3R2me2a), are decreased NAc mice rats after repeated exposure,...
Summary We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies disruptive variants in individuals ascertained for severe neurodevelopmental delay, while 53 ASD; comparing ASD cases mutations groups reveals phenotypic differences....
Many of the long-term effects cocaine on brain's reward circuitry have been shown to be mediated by alterations in gene expression. Several chromatin modifications, including histone acetylation and methylation, implicated this regulation, but effect other modifications remains poorly understood. Poly(ADP-ribose) polymerase-1 (PARP-1), a ubiquitous abundant nuclear protein, catalyzes synthesis negatively charged polymer called poly(ADP-ribose) or PAR histones substrate proteins forms...
NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic diversification vertebrates. In this study, through combination exome sequencing autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants NTNG2; these present shared features neurodevelopmental disorder consisting global developmental delay, severe to profound intellectual disability,...
Short trinucleotide expansions at the FMR1 locus are associated with late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from X (associated longer expansions), no clear molecular explanation for these marked differences. One prevailing theory posits that shorter, premutation expansion uniquely causes extreme neurotoxic increases in mRNA (i.e., four to eightfold increases), but evidence support this hypothesis...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...
ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models several psychiatric disorders. Here, we demonstrate that Baz1b , an accessory subunit ISWI family complexes, is upregulated nucleus accumbens (NAc), a key brain reward region, both chronic cocaine-treated mice and resilient to social defeat stress. In contrast, no seen susceptible this Viral-mediated overexpression along with its associated Smarca5 mouse NAc...