A5081022208- Stress Responses and Cortisol
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Birth, Development, and Health
- Glioma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Resilience and Mental Health
- Tryptophan and brain disorders
- Metabolomics and Mass Spectrometry Studies
- SARS-CoV-2 and COVID-19 Research
- Neurofibromatosis and Schwannoma Cases
- Health, Environment, Cognitive Aging
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cognitive Abilities and Testing
- Mitochondrial Function and Pathology
- Intracerebral and Subarachnoid Hemorrhage Research
- Anesthesia and Neurotoxicity Research
- Radiomics and Machine Learning in Medical Imaging
- Meningioma and schwannoma management
- COVID-19 Clinical Research Studies
- Adipose Tissue and Metabolism
- Racial and Ethnic Identity Research
- Ferroptosis and cancer prognosis
- Spine and Intervertebral Disc Pathology
Icahn School of Medicine at Mount Sinai
2020-2025
Yale University
2022-2024
Mount Sinai Health System
2024
Allen Institute for Brain Science
2021-2023
Linkou Chang Gung Memorial Hospital
2023
Salk Institute for Biological Studies
2023
Mount Sinai Medical Center
2021
University of Southern California
2019
Broad Center
2018-2019
Abstract Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute individual clinical outcomes is unknown. Here, we compared transcriptional responses hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD ( n = 19 hiPSC 20 PBMC donors) controls donors). In only, observed...
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with diverse etiologies. Therefore, the identification of common mechanisms and therapeutics targeting these could dramatically improve clinical outcomes. To this end, we developed induced (iMN) models from C9ORF72 sporadic ALS (sALS) patients to identify targets that are effective against types cases, which together comprise ~90% patients. We find iMNs several share two defects - impaired autophagosome formation aberrant...
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 Background Patients with malignancy are particularly vulnerable to infection Severe Acute Respiratory Disease‐Coronavirus‐2 (SARS‐CoV‐2) given their immunodeficiency secondary underlying disease and cancer‐directed therapy. We report a case series of patients cancer who received convalescent plasma, an investigational therapy for severe Coronavirus Disease 2019 (COVID‐19). Methods were identified plasma. Enrolled had confirmed COVID‐19 or life‐threatening transfused plasma from...
Funding: The INSIGHT Registry is funded by Penumbra. Introduction: Thrombi have shown to modify and be modified their microenvironment throughout the pathogenesis of ischemic stroke. molecular mechanisms which this occurs how it corresponds symptomatic presentation unknown. Here, we identify a transcriptomic signature in thrombi associated with increased NIHSS severity at presentation, suggesting mechanistic role for immune clearance clinical Methods: registry prospective, multicenter,...
Funding: The INSIGHT Registry is funded by Penumbra. Introduction: Rapid and precise determination of the etiology acute ischemic stroke crucial in long-term management prevention recurrence. Identification etiology-associated molecular biomarkers following thrombectomy may allow for personalized intervention. Here, we examine transcriptomics cardioembolic thrombi as a result atrial fibrillation, identifying distinct transcriptomic signature relative to other causes stroke. Methods: registry...
Introduction: Vein of Galen malformations (VOGM) are embryonic choroid plexus-derived arteriovenous which may develop secondary to mosaicism. Sequencing peripheral whole blood is often ineffective in identifying novel mutations responsible for VOGM development. Whole typically considered be a transcriptionally homogenous tissue, although vascular microenvironments impart site-specific transcriptional changes. Here, we investigated whether peripherally collected samples would yield different...
Introduction: Vein of Galen malformations (VOGM) are challenging congenital arteriovenous (AVMs) to treat. During management, for unknown reasons, VOGM may develop fine angiogenic networks feeding vessels within subarachnoid spaces. This is associated with increased symptom burden and complicates treatment. Here, we temporally characterized the evolution during endovascular therapy investigate changes in gene expression onset cessation angiogenesis. Methods: Whole blood was prospectively...
Introduction: The optimal therapeutic window for evacuation of intracerebral hemorrhage (ICH) is controversial, balancing risk prolonged exposure to blood-induced neurotoxicity against post-operative rebleeding. Pharmacologic mitigators have the potential lengthen this window, extending opportunity favorable surgical outcomes. Here, we identify a transcriptomic signature in an organoid model ICH and perform silico screen reversers toxicity. Methods: Single-cell RNA sequencing was performed...
Chronic pain, defined as pain that persists for greater than three months, is a common, understudied condition affect an estimated 20-30% of the population. Despite high prevalence and distressing physical psychological symptoms, research lacking in appropriate long-term pharmaceutical treatment chronic at rates even with intervention. Recent genome-wide association studies (GWAS) indicate can be studied distinct neuropsychiatric illness genetic risk. Here we develop genetics-informed...
INTRODUCTION: Accurate preoperative prediction of histopathological and molecular profiles diffuse gliomas using MRI images could be essential for personalized treatment planning. METHODS: The TCGA-GBM TCGA-LGG datasets were used analysis. Radiomic features extracted PyRadiomics from T1, T1 with contrast, T2, FLAIR sequences. LASSO regression was employed feature selection. TabPFN algorithm model development, a 10-repeat stratified 5-fold-cross-validation approach evaluation. A framework...
INTRODUCTION: Lumbar disc degeneration is heritable, with twin studies estimating a heritability of up to 74%. Despite family history explaining substantial proportion variance in incidence, severity, and progression, little known about the genetic variants underlying risk how they functionally contribute disease. METHODS: We applied transcriptomic imputation methods identify tissue-specific drivers lumbar from static genotypes. skeletal muscle spinal cord-specific models (from GTEx...
INTRODUCTION: Cervical myelopathy is a degenerative spinal condition that can lead to severe neurological dysfunction. Despite its pathophysiology, family history has shown be largely important factor in incidence and progression, suggesting inherent genetic predisposition may play role pathophysiology. METHODS: In large, diverse, urban biobank of 32,031 individuals, with 558 individuals cervical myopathy, we applied transcriptomic imputation identify genetically regulated gene expression...
Genetic studies of schizophrenia (SCZ) reveal a complex polygenic risk architecture comprised hundreds variants, the majority which are common in population at-large and confer only modest increases disorder risk. Precisely how genetic variants with individually small predicted effects on gene expression combine to yield substantial clinical impacts aggregate is unclear. Towards this, we previously reported that combinatorial perturbation four SCZ genes ("eGenes", whose regulated by...
To explain why individuals exposed to identical stressors experience divergent clinical outcomes, we determine how molecular encoding of stress modifies genetic risk for brain disorders. Analysis post-mortem (n=304) revealed 8557 stress-interactive expression quantitative trait loci (eQTLs) that dysregulate 915 eGenes in response stress, and lie stress-related transcription factor binding sites. Response is robust across experimental paradigms: up 50% validate glucocorticoid treated...
ABSTRACT Genetic studies of schizophrenia reveal a complex polygenic risk architecture comprised hundreds variants; most are common in the population at-large, non-coding, and act by genetically regulating expression one or more gene targets (“eGenes”). It remains unclear how genetic variants predicted to confer individually small effects combine yield substantial clinical impacts aggregate. Here, we demonstrate that eGenes have shared downstream transcriptomic (“convergence”) may underlie...
Abstract Background Chronic pain affects one fifth of American adults, contributing significant public health burden. mechanisms can be further understood through investigating brain gene expression. Methods We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, with genetic risk four regions (dACC, DLPFC, MeA, BLA) imputed cell type expression data from 304 postmortem donors. compared findings across traits independent...
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...