A5000558908- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Zebrafish Biomedical Research Applications
- Circadian rhythm and melatonin
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Wnt/β-catenin signaling in development and cancer
- Sleep and Wakefulness Research
- Molecular Biology Techniques and Applications
- Neurogenesis and neuroplasticity mechanisms
- Advanced Fluorescence Microscopy Techniques
- Ethics and Legal Issues in Pediatric Healthcare
- Neural dynamics and brain function
- Genetic Syndromes and Imprinting
- Health, Environment, Cognitive Aging
- Spaceflight effects on biology
- RNA modifications and cancer
- MicroRNA in disease regulation
Lieber Institute for Brain Development
2021-2025
Johns Hopkins Medicine
2022-2023
Johns Hopkins University
2022-2023
The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data...
Abstract The molecular organization of the human neocortex has been historically studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally-defined domains that move beyond classic cytoarchitecture. Here we used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex (DLPFC). Integration with paired single nucleus...
Drugs of abuse activate defined neuronal populations in reward structures such as the nucleus accumbens (NAc), which promote enduring synaptic, circuit, and behavioral consequences drug exposure. While molecular cellular effects arising from experience with drugs like cocaine are increasingly well understood, mechanisms that dictate NAc recruitment remain unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling targeted situ detection to identify Reln (encoding secreted...
Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety behavioral...
Cellular deconvolution of bulk RNA-sequencing (RNA-seq) data using single cell or nuclei RNA-seq (sc/snRNA-seq) reference is an important strategy for estimating type composition in heterogeneous tissues, such as human brain. Computational methods have been developed and benchmarked against simulated data, pseudobulked sc/snRNA-seq immunohistochemistry data. A major limitation developing improved algorithms has the lack integrated datasets with orthogonal measurements gene expression...
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,...
Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety behavioral...
Abstract We define and identify a new class of control genes for next-generation sequencing called total RNA expression (TREGs), which correlate with abundance in cell types different sizes transcriptional activity. provide data-driven method to TREGs from single-cell data, allowing the estimation amount when restricted quantifying limited number genes. demonstrate our postmortem human brain using multiplex single-molecule fluorescent situ hybridization compare candidate against classic...
Norepinephrine (NE) neurons in the locus coeruleus (LC) project widely throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety behavioral functions, detailed...
Abstract Next-generation sequencing technologies have facilitated data-driven identification of gene sets with different features including genes stable expression, cell-type specific or spatially variable expression. Here, we aimed to define and identify a new class “control” called Total RNA Expression Genes (TREGs), which correlate total abundance in heterogeneous cell types sizes transcriptional activity. We provide method TREGs from single RNA-sequencing (RNA-seq) data, available as an...
Abstract Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety...
Summary Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote enduring synaptic, circuit, and behavioral consequences drug exposure. While molecular cellular effects arising from experience with drugs like cocaine increasingly well understood, mechanisms that sculpt NAc ensemble participation largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling identify expression...
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...
Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety behavioral...