A5000640857- Multiple Sclerosis Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Functional Brain Connectivity Studies
- Epigenetics and DNA Methylation
- interferon and immune responses
- Retinoids in leukemia and cellular processes
- Neurological Disease Mechanisms and Treatments
- Cytomegalovirus and herpesvirus research
- Psoriasis: Treatment and Pathogenesis
- Nutrition, Genetics, and Disease
- Immune cells in cancer
- Vestibular and auditory disorders
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Folate and B Vitamins Research
- Advanced Neuroimaging Techniques and Applications
- Immune Response and Inflammation
- Sphingolipid Metabolism and Signaling
- Immunotherapy and Immune Responses
Columbia University Irving Medical Center
2017-2024
Columbia University
2021-2022
Tehran University of Medical Sciences
2012-2018
Broad Institute
2017-2018
Centre for Addiction and Mental Health
2015-2018
Sina Hospital
2014-2018
University of Toronto
2015-2018
Imam Khomeini Hospital
2015-2016
McGill University
2016
Thomas Jefferson University
2016
Abstract Microglia, the resident immune cells of brain, have important roles in brain health. However, little is known about regulation and consequences microglial activation aging human brain. Here we report that proportion morphologically activated microglia (PAM) postmortem cortical tissue strongly associated with β-amyloid, tau-related neuropathology, rate cognitive decline. Effect sizes for PAM measures are substantial, comparable to APOE ε4, strongest genetic risk factor Alzheimer’s...
Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are limited languages other than English. We aimed to translate, cross-culturally adapt, validate, assess reliability of Minimal Assessment Function MS (MACFIMS) Persian. The MACFIMS a well-constructed battery the literature. was adapted Persian accordance with available guidelines. A total 158 patients 90 controls underwent neuropsychological assessment. For assessment re-administered subset 41 after short...
The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field. Although is necessary pathologic diagnosis AD, it not sufficient to make or cause dementia. We sought identify genetic modifiers relation cortical burden (measured using [18F]Florbetapir-PET) dysfunction ADAS-cog) by conducting genome-wide interaction study on baseline data from participants in Disease Neuroimaging Initiative (ADNI) phases...
Neuromyelitis optica (NMO) exhibits substantial similarities to multiple sclerosis (MS) in clinical manifestations and imaging results has long been considered a variant of MS. With the advent specific biomarker NMO, known as anti-aquaporin 4, this assumption changed; however, differential diagnosis remains challenging it is still not clear whether combination neuroimaging data could be used aid decision-making. Computer-aided rapidly evolving process that holds great promise facilitate...
Abstract Human microglia play a pivotal role in neurological diseases, but few targeted therapies that directly modulate microglial state or function exist due to an incomplete understanding of heterogeneity. We use single-cell RNA sequencing profile live human from autopsies surgical resections across diverse diseases and central nervous system regions. observe divide between oxidative heterocyclic metabolism identify subsets associated with antigen presentation, motility, proliferation....
Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the fragile CSF by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh was collected from twenty-one participants two independent sites. Each sample split into fractions: one processed fresh, while second cryopreserved months and profiled after thawing. B T cell receptor also performed. Our...
<h3>Objective:</h3> To determine the motor-behavioral and neural correlates of putative functional common variants in sodium-channel Na<sub>V</sub>1.8 encoding gene (<i>SCN10A</i>) vivo patients with multiple sclerosis (MS). <h3>Methods:</h3> We recruited 161 relapsing-onset MS 94 demographically comparable healthy participants. All underwent structural MRI clinical examinations (Expanded Disability Status Scale [EDSS] Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise...
Abstract Identifying the effects of genetic variation on epigenome in disease-relevant cell types can help advance our understanding first molecular contributions susceptibility to disease onset. Here, we establish a genome-wide map DNA methylation quantitative trait loci CD4 + T-cells isolated from multiple sclerosis patients. Utilizing this colocalization analysis, identify 19 where same haplotype drives both and local methylation. We also two distant loci: chromosome 16 locus affects...
Background: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration brains patients with multiple sclerosis (MS). C3 is a central element the complement cascades. A common coding variant gene (rs2230199, C3R102G) affects activity. Objectives: To assess effects rs2230199 on MS severity using clinical, cognitive, imaging measures. Methods: In total, 161 relapse-onset (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical...
Abstract Cerebrospinal fluid (CSF) biomarkers are important for multiple sclerosis (MS) diagnosis. Moreover, absent of autopsy or biopsy tissue, CSF is the most relevant source studying immune cells involved in MS pathophysiology. Single-cell RNA sequencing (scRNA-seq) provides new opportunities to advance our understanding disease-associated changes cells. Here, using scRNA-seq data generated from 58 and 10 PBMC samples, we provide an updated atlas present human other neuroinflammatory...
Serum urate levels have been associated with risk for and progression of Parkinson's disease (PD). Urate-related compounds are therapeutic candidates in neuroprotective efforts to slow PD progression. A urate-elevating agent is currently under investigation as a potential disease-modifying strategy people PD. However, heterogeneous disorder, genetic variation may explain divergence severity progression.We conducted genome-wide association study identify gene variant × serum interaction...
Abstract Microglia, the resident immune cells of brain, have important roles in brain health. However, little is known about regulation and consequences microglial activation aging human brain. We assessed effect by calculating proportion activated microglia (PAM), based on morphologically defined stages four regions sampled postmortem from up to 225 elderly individuals. found that cortical not subcortical PAM measures were strongly associated with β-amyloid, tau-related neuropathology,...
Abstract The polygenic and multi-cellular nature of multiple sclerosis (MS) immunopathology necessitates cell-type-specific molecular studies in order to improve our understanding the diverse mechanisms underlying immune cell dysfunction MS. Here, by generating a dataset 1,075 transcriptomes from 209 participants (167 MS 42 healthy), we assessed MS-associated transcriptional changes six implicated cell-type-states: naïve memory helper T cells classical monocytes purified peripheral blood,...