A5036110952- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Autism Spectrum Disorder Research
- CRISPR and Genetic Engineering
- Fibroblast Growth Factor Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Ubiquitin and proteasome pathways
- Kruppel-like factors research
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- interferon and immune responses
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neural Engineering
- HIV Research and Treatment
- Genetic Syndromes and Imprinting
- Signaling Pathways in Disease
- Genetic and Kidney Cyst Diseases
- IL-33, ST2, and ILC Pathways
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Rare Diseases
- Genetics, Aging, and Longevity in Model Organisms
John Brown University
2012-2025
Brown University
2012-2024
Allen Institute for Brain Science
2012-2024
University of South Carolina
2015-2023
University of South Carolina Sumter
2022
Bradley Hospital
2015
Harvard University
2008-2014
Howard Hughes Medical Institute
2001-2014
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2014
Boston Children's Hospital
2014
Microcephaly affects ∼1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures. We analyzed mechanisms underlying brain size determination a mouse model human microcephaly. The Hertwig's anemia (an) mutant shows peripheral blood cytopenias, spontaneous aneuploidy predisposition to hematopoietic tumors. found that an mutation genomic inversion exon 4 Cdk5rap2, resulting in-frame deletion from mRNA. finding CDK5RAP2 mutations cause microcephaly...
Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well seizures, suggesting shared developmental mechanisms. regulates multiple intracellular signaling pathways, found its strongest effect be on transcription factor nuclear...
Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed males than females. Core features of ASD are impaired social interactions, repetitive behaviors deficits verbal communication. a highly heterogeneous heritable disorder, yet its underlying genetic causes account only for up to 80% the cases. Hence, subset cases could be influenced by environmental risk factors. Maternal immune activation (MIA) response inflammation during pregnancy, which can lead increased...
While genetic screens have identified many genes essential for neurite outgrowth, they been limited in their ability to identify neural that also earlier critical roles the gastrula, or which maternally contributed RNA compensates gene mutations zygote. To address this, we developed methods screen Drosophila genome using RNA-interference (RNAi) on primary cells and present results of first full-genome RNAi neurons. We used live-cell imaging quantitative image analysis characterize...
Significance We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) a neurological syndrome involving intellectual disability, reduced brain growth, and progressive motor symptoms. show that inactivate enzyme. GPT2 catalyzes reversible addition of an amino group from to pyruvate, yielding alanine α-ketoglutarate. The gene demonstrates expression postnatally, protein localizes mitochondria. As humans, Gpt2 -null mice exhibit growth. Furthermore, mutant...
To understand brain phenotypes associated with ASH1L, we used a mouse model, performing analysis in different genetic backgrounds: C57BL/6 and CD-1. We found that both lines, ASH1L mutations result seizures. Mice from lines have microcephaly, also less complex dendritic morphology. differential effects of between CD-1 strains on number measures identifying aspects function may be influenced by background. When analyzed human subjects based biological sex, for epilepsy, intellectual...
Neurons from patient-derived iPSCs demonstrate mutation-specific responses to potential therapeutic strategies for Christianson syndrome.
Autism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants ASD. Disruption of the chromatin environment leads to widespread dysregulation gene expression, which is traditionally thought as a mechanism disease pathogenesis associated with Alternatively, alterations dynamics could also lead alternative splicing, understudied ASD pathogenesis. The anticonvulsant valproic acid (VPA) well-known...
Maskin is the Xenopus homolog of transforming acidic coiled coil (TACC)-family microtubule and centrosome-interacting proteins. Members this family share a ∼200 amino acid motif at their C-termini, but have only limited homology outside domain. In all species examined thus far, perturbations TACC proteins lead to disruptions cell cycle progression and/or embryonic lethality. Drosophila, Caenorhabditis elegans, humans, these been attributed mitotic spindle assembly defects, in organisms are...
Abstract Christianson syndrome (CS) is an X-linked disorder resulting from loss-of-function mutations in SLC9A6 , which encodes the endosomal Na + /H exchanger 6 (NHE6). Symptoms include early developmental delay, seizures, intellectual disability, nonverbal status, autistic features, postnatal microcephaly, and progressive ataxia. Neuronal development impaired CS, involving defects neuronal arborization synaptogenesis, likely underlying diminished brain growth postnatally. In addition to...
Research Article19 October 2017Open Access Transparent process iPhemap: an atlas of phenotype to genotype relationships human iPSC models neurological diseases Ethan W Hollingsworth Laboratory for Neural Stem Cells and Functional Neurogenetics, Division Neuroimmunology Multiple Sclerosis, The Ohio State University Wexner Medical Center, Columbus, OH, USA Departments Neurology Neuroscience, Search more papers by this author Jacob E Vaughn Josh C Orack Chelsea Skinner Jamil Khouri Sofia B...
Abstract HIV-1 Associated Neurocognitive Disorder (HAND) is commonly seen in HIV-infected patients. Viral proteins including Tat cause neuronal toxicity and worsened by drugs of abuse. To uncover potential targets for anti-HAND therapy, we employed a literature mining system, MOLIERE. Here, validated Dead Box RNA Helicase 3 (DDX3) as target to treat HAND via selective DDX3 inhibitor, RK-33. The combined neurotoxicity protein cocaine was blocked RK-33 rat mouse cortical cultures....
Microcephaly affects approximately 1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures. We analyzed mechanisms underlying brain size determination a mouse model human microcephaly. The Hertwig's anemia (an) mutant shows peripheral blood cytopenias, spontaneous aneuploidy predisposition to hematopoietic tumors. found that an mutation genomic inversion exon 4 Cdk5rap2, resulting in-frame deletion from mRNA. finding CDK5RAP2 mutations cause...
The cerebral cortex directs higher cognitive functions. This six layered structure is generated in an inside-first, outside-last manner, which the first born neurons remain closer to ventricle while last migrate past towards surface of brain1. In addition neuronal migration2, a key process for normal cortical function regulation morphogenesis3. While morphogenesis can be studied vitro primary cultures, there much learned from how these processes are regulated tissue environments. We describe...
Precise regulation of the chromatin environment through post-translational histone modification modulates transcription and controls brain development. Not surprisingly, mutations in a large number histone-modifying enzymes underlie complex disorders. In particular, methyltransferase ASH1L modifies marks linked to transcriptional activation has been implicated multiple neuropsychiatric However, mechanisms underlying pathobiology ASH1L-asociated disease remain underexplored. We generated...