A5048087515- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- SARS-CoV-2 and COVID-19 Research
- Genomics and Chromatin Dynamics
- Genetic Mapping and Diversity in Plants and Animals
- Chromosomal and Genetic Variations
- Alkaloids: synthesis and pharmacology
- Neuroscience and Neural Engineering
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Stress Responses and Cortisol
- HIV Research and Treatment
- Nutrition, Genetics, and Disease
- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Estrogen and related hormone effects
- Acute Myocardial Infarction Research
- Cytomegalovirus and herpesvirus research
- Adipose Tissue and Metabolism
- Venous Thromboembolism Diagnosis and Management
- Antiplatelet Therapy and Cardiovascular Diseases
Icahn School of Medicine at Mount Sinai
2020-2025
Allen Institute for Brain Science
2020-2025
New York Proton Center
2022
The host response to SARS-CoV-2, the etiologic agent of COVID-19 pandemic, demonstrates significant interindividual variability. In addition showing more disease in males, elderly, and individuals with underlying comorbidities, SARS-CoV-2 can seemingly afflict healthy profound clinical complications. We hypothesize that, viral load antibody repertoire, genetic variants influence vulnerability infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models CRISPR engineering...
Abstract Dynamic interactions of neurons and glia in the ventral midbrain mediate reward addiction behavior. We studied gene expression 212,713 single nuclei from 95 individuals with history opioid misuse, without drug exposure. Chronic exposure to opioids was not associated change proportions glial neuronal subtypes, however transcriptomes were broadly altered, involving 9.5 − 6.2% expressed genes within microglia, oligodendrocytes, astrocytes. Genes activation immune response including...
Abstract Background Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain’s neuronal population and mediate cognition, food intake, metabolism. MDN are also posited to underlay neurobiological dysfunction schizophrenia (SCZ), a severe neuropsychiatric disorder that is characterized by psychosis as well multifactorial medical co-morbidities, including metabolic disease, contributing markedly increased morbidity mortality. Paradoxically, however, genetic risk sequences traits...
Abstract Regulatory mechanisms associated with repeat-rich sequences and chromosomal conformations in mature neurons remain unexplored. Here, we map cell-type specific chromatin domain organization adult mouse cerebral cortex report strong enrichment of Endogenous Retrovirus 2 (ERV2) repeat the neuron-specific heterochromatic B NeuN+ megabase-scaling subcompartment. Single molecule long-read sequencing comparative Hi-C contact mapping wild-derived SPRET/EiJ ( Mus spretus ) laboratory inbred...
ABSTRACT The host response to SARS-CoV-2, the etiologic agent of COVID-19 pandemic, demonstrates significant inter-individual variability. In addition showing more disease in males, elderly, and individuals with underlying co-morbidities, SARS-CoV-2 can seemingly render healthy profound clinical complications. We hypothesize that, viral load antibody repertoire, genetic variants also impact vulnerability infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models...
Dynamic interactions of neurons and glia in the ventral midbrain (VM) mediate reward addiction behavior. We studied gene expression 212,713 VM single nuclei from 95 human opioid overdose cases drug-free controls. Chronic exposure to opioids left numerical proportions glial neuronal subtypes unaltered, while broadly affecting transcriptomes, involving 9.5 - 6.2% expressed genes within microglia, oligodendrocytes, astrocytes, with prominent activation immune response including interferon, NFkB...
ABSTRACT Dopaminergic neurons are critical to movement, mood, addiction, and stress. Current techniques for generating dopaminergic from human induced pluripotent stem cells (hiPSCs) yield heterogenous cell populations with variable purity inconsistent reproducibility between donors, hiPSC clones, experiments. Here, we report the rapid (5 weeks) efficient (~90%) induction of (iDANs) through transient overexpression lineage-promoting transcription factors combined stringent selection across...
<title>Abstract</title> Ventral midbrain dopaminergic neurons are a key cell type for schizophrenia pathophysiology but information about type-specific genomic dysregulation in diseased brains is missing. We generated unique functional genomics resource with 111 RNA-seq and 34 Hi-C chromosomal contact libraries Nurr1+/NeuN + their surrounding Nurr1-/NeuN- nuclei, collected from donors diagnosed (SCZ) compared to neurotypical controls bipolar disorder (BD). Among the N = 340 dopamine neuron...
ABSTRACT Opioid dependence is a highly heterogeneous disease driven by variety of genetic and environmental risk factors which have yet to be fully elucidated. We interrogated the effects opioid on brain using ChIP-seq quantify patterns H3K27 acetylation in dorsolateral prefrontal cortical neurons isolated from 51 opioid-overdose cases accidental death controls. Among cases, we observed global hypoacetylation identified 388 putative enhancers consistently depleted for H3K27ac. Machine...
Abstract Exploration of genome organization and function in the HIV infected brain is critical to aid development treatments for HIV-associated neurocognitive disorder (HAND) cure strategies. Here, we generated a resource comprised single nuclei transcriptomics, complemented by cell-type-specific Hi-C chromosomal conformation (‘3D genome’) viral integration site sequencing (IS-seq) frontal tissues from individuals with encephalitis (HIVE), HIV-infected people without (HIV+), uninfected...
Abstract Cigarette smoking and alcohol use are among the most prevalent substances used worldwide account for a substantial proportion of preventable morbidity mortality, underscoring public health significance understanding their etiology. Genome-wide association studies (GWAS) have successfully identified genetic variants associated with cigarette traits. However, vast majority risk reside in non-coding regions genome, target genes neurobiological mechanisms unknown. Chromosomal...