A5029194549- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genetic Associations and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- Genetics and Physical Performance
- Bioinformatics and Genomic Networks
- Neurological Disease Mechanisms and Treatments
- RNA Research and Splicing
- Immune cells in cancer
- Gene expression and cancer classification
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Diabetes and associated disorders
- Neuroblastoma Research and Treatments
- Error Correcting Code Techniques
- Genetic Mapping and Diversity in Plants and Animals
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Congenital Ear and Nasal Anomalies
- Hedgehog Signaling Pathway Studies
- ATP Synthase and ATPases Research
- Ginkgo biloba and Cashew Applications
Washington University in St. Louis
2021-2024
University of Michigan
2016-2022
Hope Center for Neurological Disorders
2021-2022
Michigan United
2018
Universidade Federal do Rio Grande do Sul
2013-2014
Instituto de Saúde
2014
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, pathogenic mechanisms most these remain elusive. Here, we examined genomic, epigenomic, transcriptomic profiles in human pancreatic islets to understand links between genetic variation, chromatin landscape, gene expression context T2D. We first integrated genome transcriptome variation across 112 islet samples produce dense cis-expression...
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, cell-specific effect these is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from parietal cortex AD autosomal dominant (APP PSEN1) risk-modifying variant (APOE, TREM2 MS4A) carriers. Within individual cell types, capture commonly dysregulated across groups. specific...
Abstract Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of >100 variants associated with T2D related traits in genome-wide association studies (GWAS), >90% occur non-coding regions, suggesting a strong regulatory component to risk. Here understand how status, metabolic variation influence gene expression, we analyse skeletal muscle biopsies 271 well-phenotyped Finnish participants glucose tolerance ranging...
Abstract Genome-wide association studies (GWAS) have identified many modifiers of Alzheimer disease (AD) risk enriched in microglia. Two these are common variants the MS4A locus (rs1582763: protective and rs6591561: risk) serve as major regulators CSF sTREM2 levels. To understand their functional impact on AD, we used single nucleus transcriptomics to profile brains from carriers variants. We discovered a “chemokine” microglial subpopulation that is altered variant for which MS4A4A...
Abstract Interactions between transcription factors and chromatin are fundamental to genome organization regulation and, ultimately, cell state. Here, we use information theory measure signatures of organized resulting from factor-chromatin interactions encoded in the patterns accessible genome, which term enrichment (CIE). We calculate CIE for hundreds factor motifs across human samples identify two classes: low high CIE. The 10–20% common tissue-specific motifs, associate with higher...
Abstract CHARGE syndrome, a rare multiple congenital anomaly condition, is caused by haploinsufficiency of the chromatin remodeling protein gene CHD7 (Chromodomain helicase DNA binding 7). Brain abnormalities and intellectual disability are commonly observed in individuals with CHARGE, neuronal differentiation reduced patient-derived iPSCs conditional knockout mouse brains. However, mechanisms function nervous system development not well understood. In this study, we asked whether promotes...
In tropical America, principally in Northeastern Brazil, the leaf extract of Anacardium occidentale is traditionally used for treatment different diseases. However, chemical and biological properties activities are poorly investigated known. Here, we evaluated antioxidant anti‐inflammatory “in vitro” from occidentale. Our results show that exhibits activity when to treat RAW 264.7 macrophage cells. Antioxidant effects were observed by decrease oxidative damage cells treated with 0.5 µ g/mL 5...
Abstract Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved, has been challenging. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles gene expression chromatin accessibility in healthy autoantibody+ (AAB+) human pancreatic...
Computational analyses identified<italic>TULP3</italic>as a master regulator of transcription in PDAC expression data and moreover its regulated genes, giving<italic>TULP3</italic>prognostic value.
From whole organisms to individual cells, responses environmental conditions are influenced by genetic makeup, where the effect of variation on a trait depends context. RNA-sequencing quantifies gene expression as molecular trait, and is capable capturing both effects. In this study, we explore opportunities using allele-specific (ASE) discover cis-acting genotype-environment interactions (GxE)—genetic effects that depend an condition. Treating 17 common, clinical traits approximations...
In vertebrates, multiple transcription factors (TFs) bind to gene regulatory elements (promoters, enhancers, and silencers) execute developmental expression changes. ChIP experiments are often used identify where TFs in the genome, but requirement of TF-specific antibodies hampers analyses tens at loci. Here we tested whether TF binding predictions using ATAC-seq can be infer identity that functionally validated enhancers Cd4, Cd8, Gata3 genes thymocytes. We performed four distinct stages...
In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types chronic diseases, such diabetes, hypertension, pain, and general inflammation. Despite its widespread use, little known about medicinal properties plants this genus. study, we evaluate antioxidant anti-inflammatory T. vitro model inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We...
Abstract The genetic determinants of fasting glucose (FG) and insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole sequencing analyses from fifteen cohorts NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals five race-ethnicities/populations (African, Asian, European, Hispanic Samoan) were included. Eight variants significantly FG or FI across...
Neuroblastoma is the most common extracranial tumor and a major cause of infant cancer mortality worldwide. Despite its importance, little known about molecular mechanisms. A striking feature this clinical heterogeneity. Possible outcomes range from aggressive invasion to other tissues, causing patient death, spontaneous disease regression or differentiation into benign ganglioneuromas. Several efforts have been made in order find progression markers. In work, we reconstructed neuroblastoma...
Abstract Cellular crosstalk, mediated by membrane receptors and their ligands, is crucial for brain homeostasis can contribute to neurodegenerative diseases such as Alzheimer’s disease (AD). To discover crosstalk dysregulations in AD, we reconstructed networks from single-nucleus transcriptional profiles 67 clinically neuropathologically well-characterized controls AD donors. We predicted a significant role TREM2 additional risk genes mediating neuron-microglia AD. The gene sub-network...
Identifying the tissue-specific molecular signatures of active regulatory elements is critical to understand gene mechanisms. Here, we identify transcription start sites (TSS) using cap analysis expression (CAGE) across 57 human pancreatic islet samples. We 9,954 reproducible CAGE tag clusters (TCs), ∼20% which are specific and occur mostly distal known TSS. integrated data with histone modification chromatin accessibility profiles epigenomic initiation. Using a massively parallel reporter...
Abstract Background Alzheimer disease (AD) has substantial genetic, molecular, and cellular heterogeneity associated with its etiology. Much of our current understanding the main AD molecular events amyloid hypothesis ( APP, PSEN1 PSEN2 ) neuroimmune modulation TREM2 MS4A is based on genetic studies including GWAS. However, functional genes, downstream transcriptional ramifications, cell-type-specific effects many GWAS loci remain poorly understood. Understanding these can point us to...
Orthology information has been used for searching patterns in high-dimensional data, allowing transferring functional between species. The key concept behind this strategy is that orthologous genes share ancestry to some extent. While reconstructing the history of a single gene feasible with existing computational resources, reconstruction entire biological systems remains challenging. In study, we present Bridge, new algorithm designed infer evolutionary root large-scale analyses. Bridge...
Type 2 diabetes is increasing in all ancestry groups 1 . Part of its genetic basis may reside among the rare (minor allele frequency <0.1%) variants that make up vast majority human variation We analyzed high-coverage (mean depth 38.2x) whole genome sequencing from 9,639 individuals with T2D and 34,994 controls NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program to show rare, non-coding are poorly captured by genotyping arrays or imputation panels contribute h =53% (P=4.2×10 −5 )...
Sepsis remains a leading cause of death in ICUs all over the world, with pediatric sepsis accounting for high percentage mortality ICUs. Its complexity makes it difficult to establish consensus on genetic biomarkers and therapeutic targets. A promising strategy is investigate regulatory mechanisms involved progression, but there are few studies regarding gene regulation sepsis. This work aimed reconstruct network identify transcription factors (TFs) driving transcriptional states, which we...
Chemoreception is among the most important sensory modalities in animals. Organisms use ability to perceive chemical compounds all major ecological activities. Recent studies have allowed characterization of chemoreceptor gene families. These genes present strikingly high variability copy numbers and pseudogenization degrees different species, but mechanisms underlying their evolution are not fully understood. We analyzed functional networks these genes, orthologs distribution, performed...