A5043364190- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Cell Image Analysis Techniques
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Epigenetics and DNA Methylation
- interferon and immune responses
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Gene expression and cancer classification
- Bone Metabolism and Diseases
- Histone Deacetylase Inhibitors Research
- Bioinformatics and Genomic Networks
- Spectroscopy Techniques in Biomedical and Chemical Research
- Memory and Neural Mechanisms
- Autophagy in Disease and Therapy
- Molecular Biology Techniques and Applications
- Genetics, Aging, and Longevity in Model Organisms
Lieber Institute for Brain Development
2021-2025
Johns Hopkins University
2025
University of Alabama at Birmingham
2016-2024
Wake Forest University
2014-2018
The lateral septum (LS) is a midline, subcortical structure that critical regulator of social behaviors. Mouse studies have identified molecularly distinct neuronal populations within the LS, which control specific facets behavior. Despite its known molecular heterogeneity in mouse and role regulating behavior, comprehensive profiling human LS has not been performed. Here, we conducted single-nucleus RNA sequencing (snRNA-seq) to generate transcriptomic profiles compared recently collected...
CRISPR-based technology has provided new avenues to interrogate gene function, but difficulties in transgene expression post-mitotic neurons delayed incorporation of these tools the central nervous system (CNS). Here, we demonstrate a highly efficient, neuron-optimized dual lentiviral transcriptional activation (CRISPRa) capable robust, modular, and tunable induction multiplexed regulation across several primary rodent neuron culture systems. CRISPRa targeting unique promoters complex...
Proteolysis by the ubiquitin-proteasome pathway appears to have a complex role in synaptic plasticity, but its various functions remain be elucidated. Using late phase long-term potentiation (L-LTP) hippocampus of mouse as model for we previously showed that inhibition proteasome enhances induction blocks maintenance L-LTP. In this study, investigated possible mechanisms which has opposite effects on L-LTP and maintenance. Our results show inhibiting phosphatidyl inositol-3 kinase or...
Alzheimer's disease (AD) therapies predominantly focus on β-amyloid (Aβ), but Aβ effects may be maximal before clinical symptoms appear. Downstream of Aβ, dendritic spine loss correlates most strongly with cognitive decline in AD. Rho-associated kinases (ROCK1 and ROCK2) regulate the actin cytoskeleton, ROCK1 ROCK2 protein abundances are increased early Here, we found that abundance cultured primary rat hippocampal neurons reduced length through a myosin-based pathway, whereas induced serine...
Abstract The hippocampus contains many unique cell types, which serve the structure’s specialized functions, including learning, memory and cognition. These cells have distinct spatial topography, morphology, physiology, connectivity, highlighting need for transcriptome-wide profiling strategies that retain cytoarchitectural organization. Here, we generated spatially-resolved transcriptomics (SRT) single-nucleus RNA-sequencing (snRNA-seq) data from adjacent tissue sections of anterior human...
Abstract Brain‐derived neurotrophic factor ( Bdnf ) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well learning and memory. The rodent gene contains nine 5′ non‐coding exons I – IXa ), which are spliced to common 3′ coding exon IX ). Transcription of individual variants, all encode the same BDNF protein, is initiated at unique promoters upstream each exon, enabling precise spatiotemporal activity‐dependent regulation expression. Although prior evidence...
The expression of genetic material governs brain development, differentiation, and function, targeted manipulation gene is required to understand contributions function health disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled transcriptional repression at selected genomic sites, integrating these techniques for use non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus system express CRISPR-based...
Abstract Pathophysiology of many neuropsychiatric disorders, including schizophrenia (SCZD), is linked to habenula (Hb) function. While pharmacotherapies and deep brain stimulation targeting the Hb are emerging as promising therapeutic treatments, little known about cell type-specific transcriptomic organization human or how it altered in SCZD. Here we define molecular neuroanatomy identify changes individuals with SCZD compared neurotypical controls. Utilizing Hb-enriched postmortem tissue,...
Recent developments in CRISPR-based gene editing have provided new avenues to interrogate function. However, application of these tools the central nervous system has been delayed due difficulties transgene expression post-mitotic neurons. Here, we present a highly efficient, neuron-optimized dual lentiviral transcriptional activation (CRISPRa) drive primary neuronal cultures and adult brain rodent model systems. We demonstrate robust, modular, tunable induction endogenous target genes as...
The lateral septum (LS) is a midline, subcortical structure, which regulates social behaviors that are frequently impaired in neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Mouse studies have identified neuronal populations within the LS express variety of molecular markers, vasopressin receptor, oxytocin corticotropin releasing hormone control specific facets behavior. Despite its critical role regulating behavior notable gene expression patterns,...
Abstract Background Multispectral fluorescence imaging coupled with linear unmixing is a form of image data collection and analysis that allows for measuring multiple molecular signals in single biological sample. Multiple fluorescent dyes, each unique molecule, are simultaneously measured subsequently “unmixed” to provide read-out signal. This strategy highly multiplexed capture session, such as proteins or RNAs tissue slices cultured cells, but can often result mixed bleed-through problems...
The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular anatomical features that are specialized in amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis constituent cell populations. We analyzed five nuclear subdivisions primate with single-nucleus RNA sequencing macaques, baboons, humans to examine gene expression profiles for excitatory inhibitory neurons confirmed our results single-molecule FISH...
Summary Brain-derived neurotrophic factor ( Bdnf ) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well learning and memory. The rodent gene contains nine 5′ non-coding exons I-IXa ), which are spliced to common 3′ coding exon IX ). Transcription of individual variants, all encode the same BDNF protein, is initiated at unique promoters upstream each exon, enabling precise spatiotemporal activity-dependent regulation expression. Although prior evidence...
Abstract Background Visium is a widely-used spatially-resolved transcriptomics assay available from 10x Genomics. Standard capture areas (6.5mm by 6.5mm) limit the survey of larger tissue structures, but combining overlapping images and associated gene expression data allow for more complex study designs. Current software can handle nested or partial image overlaps, designed merging up to two areas, cannot account some technical scenarios related area alignment. Results We generated...
Abstract Background Visium is a widely-used spatially-resolved transcriptomics assay available from 10x Genomics. Standard capture areas (6.5mm by 6.5mm) limit the survey of larger tissue structures, but combining overlapping images and associated gene expression data allow for more complex study designs. Current software can handle nested or partial image overlaps, designed merging up to two areas, cannot account some technical scenarios related area alignment. Results We generated...
Abstract The hypothalamus contains multiple regions, including the ventromedial (VMH) and arcuate (ARC), which are responsible for sex-differentiated functions such as endocrine signaling, metabolism, reproductive behaviors. While molecular, anatomic, features of rodent well-established, much less is known about these regions in humans. Here we provide a spatially-resolved single cell atlas sex-differentially expressed (sex-DE) genes human VMH ARC. We identify neuronal populations governing...
The expression of genetic material governs brain development, differentiation, and function, targeted manipulation gene is required to understand contributions function health disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled transcriptional repression at selected genomic sites, integrating these techniques for use non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus system express CRISPR-based...
Alzheimer's disease (AD) therapies predominantly focus on amyloid-β (Aβ), but Aβ effects may be maximal before clinical symptoms. Downstream of Aβ, dendritic spine loss correlates most strongly with cognitive decline in AD. Synaptic strength and activity are inseparably linked to morphology. Recent discoveries indicate that structure remodeling is a plausible mechanism maintain synapses provide resilience patients an apolipoprotein E (APOE) ε4 allele and/or AD pathology. induces degeneration...