A5071928757- Circadian rhythm and melatonin
- Genetics, Aging, and Longevity in Model Organisms
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Neuroendocrine regulation and behavior
- Genetic and Kidney Cyst Diseases
- Erythrocyte Function and Pathophysiology
- Wnt/β-catenin signaling in development and cancer
- Neuroscience of respiration and sleep
- Kruppel-like factors research
- Sleep and related disorders
- Sleep and Wakefulness Research
- Fibroblast Growth Factor Research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Genetic Syndromes and Imprinting
- Cellular transport and secretion
University of Pennsylvania
2023-2024
Center for Autism and Related Disorders
2024
University of South Carolina
2018-2023
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...
Structural neuroplasticity (changes in the size, strength, number, and targets of synaptic connections) can be modified by sleep disruption. However, causal relationships between genetic perturbations, loss, neuroplasticity, behavior remain unclear. The
Neurexins are synaptic adhesion molecules that play diverse roles in development, function, maintenance, and plasticity. Neurexin genes have been associated with changes human behavior, where variants NRXN1 autism, schizophrenia, Tourette syndrome. While NRXN1, NRXN2, NRXN3 all encode major α β isoforms, uniquely encodes a γ isoform, for which mechanistic behavior yet to be defined. Here, we show both isoforms of neurexin/nrx-1 required the C. elegans behavioral response food deprivation,...
SUMMARY Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and highly heritable. Genetic findings suggest that there is an overrepresentation of chromatin regulatory genes among the ASD. ASH1 like histone lysine methyltransferase (ASH1L) was identified as a major risk factor for autism. ASH1L methylates Histone H3 on Lysine 36, which proposed to result primarily transcriptional activation. However, how mutations lead deficits autism pathogenesis not known....
ABSTRACT Animal foraging is an essential and evolutionarily conserved behavior that occurs in social solitary contexts, but the underlying molecular pathways are not well defined. We discover autism-associated genes ( NRXN1(nrx-1) , NLGN3(nlg-1) GRIA1,2,3(glr-1) GRIA2(glr-2) GLRA2,GABRA3(avr-15)) regulate aggregate feeding C. elegans a simple behavior. NRX-1 functions chemosensory neurons (ADL ASH) independently of its postsynaptic partner NLG-1 to feeding. Glutamate from these also crucial...
RAB3GAP1 is GTPase activating protein localized to the ER and Golgi compartments. In humans, mutations in are most common cause of Warburg Micro syndrome, a neurodevelopmental disorder associated with intellectual disability, microcephaly, agenesis corpus callosum. We found that downregulation leads reduction neurite outgrowth complexity human stem cell derived neurons. To further define cellular function RAB3GAP1, we sought identify novel interacting proteins. used combination mass...
Abstract Human genetic disorders provide a powerful lens to understanding the human brain. Induced pluripotent stem cells (iPSC) represent an important, new resource for mechanistic studies and therapeutic development. Christianson syndrome (CS), X-linked neurological disorder with attenuation of brain growth postnatally (postnatal microcephaly), is caused by mutations in SLC9A6, gene encoding endosomal Na + /H exchanger 6 (NHE6). We developed CS iPSC lines from patients mutational spectrum,...