A5003753203- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Gut microbiota and health
- Neuroinflammation and Neurodegeneration Mechanisms
- Aquaculture disease management and microbiota
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- Diet and metabolism studies
- SARS-CoV-2 and COVID-19 Research
- Alzheimer's disease research and treatments
- Dietary Effects on Health
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Zebrafish Biomedical Research Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Clusterin in disease pathology
- RNA regulation and disease
- Genomics and Rare Diseases
- COVID-19 Clinical Research Studies
- interferon and immune responses
HudsonAlpha Institute for Biotechnology
2020-2024
North Carolina State University
2012-2020
Indiana University School of Medicine
2017-2018
Indiana University Northwest
2017-2018
Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer's disease (AD) and unaffected controls have been well documented, but few studies rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq plus snATAC-seq) on 105,332 nuclei isolated cortical 7 AD 8 to identify candidate
Variant detection from long-read genome sequencing (lrGS) has proven to be more accurate and comprehensive than variant short-read (srGS). However, the rate at which lrGS can increase molecular diagnostic yield for rare disease is not yet precisely characterized. We performed using Pacific Biosciences HiFi technology on 96 short-read-negative probands with diseases that were suspected genetic. generated hg38-aligned variants de novo phased assemblies, subsequently annotated, filtered,...
Genetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known be resistant high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of innate immunity antibacterial gene Nod2 abolishes this resistance, as -/- developed HFD-dependent hallmark features syndrome. HFD hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, steatosis, with large lipid droplets their hepatocytes. These...
Abstract INTRODUCTION Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants therapeutic applications. We present a large Colombian kindred autosomal dominant AD (ADAD) as unique opportunity to discover AAO associations. METHODS A association study was conducted examine ADAD in 340 individuals the PSEN1 E280A mutation via TOPMed array imputation. Replication assessed two cohorts, one sporadic early‐onset and four late‐onset studies. RESULTS 13 had...
ABSTRACT Mitochondria are known primarily as the location of electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis inflammation. Reactive oxygen species (ROS) generated by-products within significantly impact cellular pathways. Because toxic nature ROS, possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), neutralize ROS. If mitochondrial enzymes overwhelmed during severe infections, dysfunction can...
Abstract An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause this rampage yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling essential for hyperinflammation, and blocking proinflammatory axis could be an effective therapeutic approach to protect against Here provide exploratory evidence abatacept, a drug blocks co-stimulation, produces changes at systemic level are highly antagonistic processes...
Abstract Background In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to chronic inflammation synovium. Here, we perform an in-depth quantitative analysis seven chains that comprise adaptive immune receptor repertoire (AIRR) in RA. Results comparison controls, show RA patients have multiple strong differences including reduced diversity as well altered isotype, chain, segment frequencies. We demonstrate therapeutic tumor necrosis factor...
Currently, assessment of the potential immunotoxicity a given agent involves tiered approach for hazard identification and mechanistic studies, including observational evaluation immune function, measurement susceptibility to infectious neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due their rapid development, ease maintenance, homology system function development. Larval zebrafish also are...
The novel immune-type receptors (NITRs), which have been described in numerous bony fish species, are encoded by multigene families of inhibitory and activating predicted to be functional orthologs the mammalian natural killer cell (NKRs). Within zebrafish NITR family, nitr9 is only gene encode an receptor. However, alternative RNA splicing generates three distinct transcripts, each encodes a different isoform. Although transcripts detected lymphocytes, specific hematopoietic lineage(s) that...
Abstract The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity system its interdependent innate adaptive functionality, an understanding whole-organism pathogen exposure remains unresolved. Zebrafish larvae a unique model for overcoming this obstacle, because are protected pathogens while lacking functional during first few weeks life. were exposed agonists various lengths...
Abstract Transcription factors (TFs) orchestrate gene expression programs crucial for cell physiology, but our knowledge of their function in the brain is limited. Using bulk tissues and sorted nuclei from multiple human post-mortem regions, we generated a multi-omic resource (1121 total experiments) that includes binding maps more than 100 TFs. We demonstrate improved measurements TF activity, including motif recognition modeling, upon identification removal regions high occupancy. Further,...
ABSTRACT Background Tauopathies are a group of neurodegenerative diseases driven by abnormal aggregates tau, microtubule associated protein encoded the MAPT gene. expression is absent in neural progenitor cells (NPCs) and increases during differentiation. This temporally dynamic pattern suggests that controlled transcription factors cis-regulatory elements specific to differentiated cell types. Given relevance neurodegeneration pathogenesis, identification such relevant understanding genetic...
Summary Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer’s disease (AD) and unaffected controls have been well-documented, but few studies rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq+snATAC-seq) on 105,332 nuclei isolated cortical 7 AD 8 to identify candidate cis -regulatory elements (CREs) involved in AD-associated changes. detected 319,861 significant...
Transcription factors (TFs) regulate gene expression by facilitating or disrupting the formation of transcription initiation machinery at particular genomic loci. Because TF occupancy is driven in part recognition DNA sequence, genetic variation can influence TF–DNA associations and regulation. To identify variants that impact binding human brain tissues, we assessed allele-specific (ASB) heterozygous for 94 TFs nine regions from two donors. Leveraging graph genomes constructed phased...
Transcription Factors (TFs) influence gene expression by facilitating or disrupting the formation of transcription initiation machinery at particular genomic loci. Because localization TFs is in part driven TF recognition DNA sequence, variation binding sites can disrupt TF-DNA associations and affect regulation. To identify variants that impact human brain tissues, we quantified allele bias for 93 analyzed with ChIP-seq experiments multiple structural regions from two donors. Using graph...
Abstract INTRODUCTION Genetic associations with Alzheimer’s disease (AD) age at onset (AAO) could reveal genetic variants therapeutic applications. We present a large Colombian kindred autosomal dominant AD (ADAD) as unique opportunity to discover AAO associations. METHODS A association study was conducted for ADAD dementia in 340 individuals the PSEN1 E280A mutation via TOPMed array imputation. Replication assessed two cohorts, one sporadic EOAD study, and four late studies. RESULTS 13 had...
In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need identify therapies treat prevent symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be effective therapeutic...
ABSTRACT Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease characterized by a defective adaptive immune receptor repertoire (AIRR) that fails to distinguish self from non-self antigens. The AIRR vast, encompassing four T cell (TCR) and three B (BCR) chains, each of which displays extraordinary amino acid sequence variability in the antigen-binding site. How concerted action clones associated with development clinical evolution diseases still not known. Using new...
Abstract Background Tau is encoded by MAPT and abnormal aggregates of tau are a hallmark many neurodegenerative diseases. highly expressed in neurons but much more lowly other cell types, including neural precursor cells (NPCs), suggesting that its expression may be controlled neuron‐specific transcription factors cis‐regulatory elements. reduction, even endogenous tau, current therapeutic strategy both model systems humans; therefore, understanding regulation point to new strategies achieve...