A5063771423- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Synthesis and properties of polymers
- Polymer crystallization and properties
- Immune cells in cancer
- biodegradable polymer synthesis and properties
- Neurological Disease Mechanisms and Treatments
- Genetic Associations and Epidemiology
- Peroxisome Proliferator-Activated Receptors
- Adsorption, diffusion, and thermodynamic properties of materials
- Bacteriophages and microbial interactions
- Dementia and Cognitive Impairment Research
- Inflammation biomarkers and pathways
- Genetic and Kidney Cyst Diseases
- Organometallic Complex Synthesis and Catalysis
- Advanced Polymer Synthesis and Characterization
- Animal Virus Infections Studies
- Ferroptosis and cancer prognosis
- Alcohol Consumption and Health Effects
- Chemical Thermodynamics and Molecular Structure
- Atmospheric aerosols and clouds
- Environmental and Industrial Safety
- Textile materials and evaluations
Icahn School of Medicine at Mount Sinai
2019-2024
Pediatrics and Genetics
2023
Allen Institute for Brain Science
2021
Purdue University West Lafayette
2016-2018
Synthetic Rubber Research Institute named after S. V. Lebedeva
1969-1987
Scientific Research Institute of the Rubber Industry
1965
Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer's disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that risk alleles are enriched in myeloid-specific epigenomic annotations. Here, show they specifically active enhancers monocytes, macrophages microglia. We integrated GWAS myeloid transcriptomic datasets using...
Abstract Genetic and experimental evidence suggests that Alzheimer’s disease (AD) risk alleles genes may influence susceptibility by altering the transcriptional cellular responses of macrophages, including microglia, to damage lipid-rich tissues like brain. Recently, sc/nRNA sequencing studies identified similar activation states in subpopulations macrophages aging degenerating brains other diseased tissues. We collectively refer these microglia peripheral as DLAMs. Using macrophage...
Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts modulate therapeutically. Here, we characterize the activities three agonist antibodies in multiple mixed-sex mouse models Alzheimer's disease (AD) pathology remyelination. Receptor activation downstream signaling are explored vitro, active dose ranges determined vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-β (Aβ)...
Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology alcohol use disorder (AUD) drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex obtain biological insights disease mechanisms. In this study, we multi-omics approaches, fine-map AUD DPW associations at single SNP resolution demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA...
New intravesical treatment approaches for bladder cancer are needed as currently approved treatments show several side effects and high tumor recurrence rate. Our study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated cellulosic nanobubbles a novel agent imaging ultrasound guided drug delivery. In this study, we that (ONB) can be propelled (up 40 mm/s) precisely in vivo the by an beam. Nanobubble velocity controlled altering power of Doppler beam, while nanobubble...
Astrocytes play a pivotal role in central nervous system homeostasis and neuroinflammation. Despite advancements single-cell analyses, the heterogeneity of reactive astrocytes neurodegenerative diseases, particularly across species, remains understudied. Here, we present an integrated atlas 187,000 from mouse models Alzheimer's (AD) multiple sclerosis (MS) alongside 438,000 AD, MS, Parkinson's (PD) patients. Our analysis identified four distinct astrocyte clusters, including two...
<title>Abstract</title> Astrocytes play a pivotal role in central nervous system homeostasis and neuroinflammation. Despite advancements single-cell analyses, the heterogeneity of reactive astrocytes neurodegenerative diseases, particularly across species, remains understudied. Here, we present an integrated atlas 187,000 from mouse models Alzheimer's (AD) multiple sclerosis (MS) alongside 438,000 AD, MS, Parkinson's (PD) patients. Our analysis identified four distinct astrocyte clusters,...
Abstract Genome-wide association studies (GWAS) have identified more than thirty loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown thus impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that risk alleles are enriched in myeloid-specific epigenomic annotations. Here, show they specifically active enhancers monocytes, macrophages microglia. We integrated GWAS signals myeloid...
Abstract Targeting of tau pathology has long been proposed as a potential therapeutic strategy for Alzheimer’s disease (AD). Semorinemab is humanized IgG4 monoclonal antibody that binds to all known isoforms full-length with high affinity and specificity. Semorinemab’s safety efficacy have studied in two Phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trials: Tauriel (prodromal-to-mild AD; NCT03289143 ) Lauriet (mild-to-moderate NCT03828747 ). CSF was collected...
The vast unexplored virus biodiversity makes the application of templates to nanomaterial synthesis especially promising. Here, a new biotemplate, Barley stripe mosaic (BSMV) was successfully used synthesize organic-metal nanorods similarly high quality those produced with Tobacco (TMV). mineralization behavior characterized in terms reduction and adsorption precursor nanocrystal formation processes. BSMV surface-mediated Pd(2+) proceeded via first-order kinetics both BSMV. equilibrium...
Abstract Background Genetic and experimental evidence strongly implicates myeloid cells in the etiology of AD suggests that AD-associated alleles genes may modulate disease risk by altering transcriptional cellular responses macrophages (like microglia) to damage lipid-rich tissues brain). Specifically, recent single-cell/nucleus RNA sequencing (sc/nRNA-seq) studies identified a transcriptionally distinct state subsets aging or degenerating brains (usually referred as disease- associated...
Abstract INTRODUCTION Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease‐modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials. METHODS We conducted multi‐omic analyses paired non‐human primate brain cerebrospinal fluid (CSF), stimulation of human induced pluripotent stem cell–derived...
Abstract Background Genome‐wide association studies (GWAS) have identified more than forty loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements and genes remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Method We used an integrative genomic approach to determine epigenomic annotations enriched for risk variants applied summary‐data based Mendelian Randomization link myeloid enhancer activity target gene expression...
In recent years, large-scale and hypothesis-free genetic studies have identified ∼30 genomic regions that pass the genome-wide significance threshold for association with Alzheimer's disease (AD). These risk loci contain hundreds of genes and, since vast majority variants in these are non-coding, it is difficult to identify causal confidence. Indeed, compelling evidence exists only a handful where functional coding been (e.g., APOE, TREM2, ABCA7), which expressed execute key functions...