A5039254521- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Influenza Virus Research Studies
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Microbial Metabolic Engineering and Bioproduction
- interferon and immune responses
- Single-cell and spatial transcriptomics
- Genetics, Aging, and Longevity in Model Organisms
- HIV Research and Treatment
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
- Pancreatic function and diabetes
- Air Quality and Health Impacts
- Congenital Diaphragmatic Hernia Studies
- vaccines and immunoinformatics approaches
- Atherosclerosis and Cardiovascular Diseases
- HIV-related health complications and treatments
- T-cell and B-cell Immunology
- Polyamine Metabolism and Applications
- Circadian rhythm and melatonin
- Evolution and Genetic Dynamics
- Health, Environment, Cognitive Aging
University of Rochester
2016-2025
University of Rochester Medical Center
2016-2025
Emory University
2019
Unifor
2019
Uniformed Services University of the Health Sciences
2016-2019
Walker (United States)
2019
Khan Academy
2019
Phipps Houses
2019
Jones College
2019
Clarkson University
2016
Modern life sciences research increasingly relies on computational solutions, from large scale data analyses to theoretical modeling. Within the models Boolean networks occupy an increasing role as they are eminently suited at mapping biological observations and hypotheses into a mathematical formalism. The conceptual underpinnings of modeling very accessible even without background in quantitative sciences, yet it allows scientists describe explore wide range surprisingly complex phenomena....
Enrichment analysis of gene sets is a popular approach that provides functional interpretation genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in high Type I error. The most widely used test, Gene Set Analysis, relies on computationally intensive permutations sample labels to generate null distribution preserves gene–gene correlations. A more recent approach, CAMERA, attempts correct for these correlations estimating variance inflation factor...
Defective viral genomes (DVGs) are generated ubiquitously in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide the potential for them be used novel antiviral therapies vaccine development.
Abstract Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA repertoire sequencing on paired synovial tissue blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + cells, including CCL5+ cells peripheral helper (Tph) which show a prominent transcriptomic signature of recent activation effector function. CD8 higher oligoclonality than with the largest clones enriched in GZMK+ possibly...
Many pathogens are able to manipulate the signaling pathways responsible for generation of host immune responses. Here we examine and model a respiratory infection system in which disruption functions or bacterial factors changes dynamics infection. We synthesize network interactions between components two closely related bacteria genus Bordetellae. incorporate existing experimental information on timing regulatory events into discrete dynamic model, verify by comparing effects simulated...
Co-infection by multiple parasites is common within individuals. Interactions between co-infecting include resource competition, direct competition and immune-mediated interactions each are likely to alter the dynamics of single parasites. We posit that co-infection a driver variation in parasite establishment growth, ultimately altering production transmission stages. To test this hypothesis, three different treatment groups laboratory mice were infected with gastrointestinal helminth...
To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age≥65) adults receiving two consecutive seasons identified those with strong or absent response to vaccine, including a subset of meeting criteria for frailty. PBMCs obtained prior vaccination (Day 0) at day 2 4, 7 28 post-vaccine were subjected microarray analysis. We defined signature also detected induction type I interferon plasma cell...
Abstract Background Neuroinflammation is thought to contribute the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We previously shown that sustained expression IL-1β hippocampus APP/PS1 mice decreases burden independent recruited CCR2 + myeloid cells, suggesting resident microglia as main phagocytic effectors IL-1β-induced To date, however, mechanisms clearance remain poorly understood....
Abstract Background Growing up on traditional, single‐family farms is associated with protection against asthma in school age, but the mechanisms early manifestations of atopic disease are largely unknown. We sought determine gut microbiome and metabolome composition rural Old Order Mennonite (OOM) infants at low risk Rochester, NY urban/suburban high for diseases. Methods In a cohort 65 OOM 39 Rochester mother‐infant pairs, 101 infant stool 61 human milk samples were assessed by 16S rRNA...
Co-infections alter the host immune response but how systemic and local processes at site of infection interact is still unclear. The majority studies on co-infections concentrate one infecting species, an function or group cells often focus initial phase infection. Here, we used a combination experiments mathematical modelling to investigate network responses against single with respiratory bacterium Bordetella bronchiseptica gastrointestinal helminth Trichostrongylus retortaeformis. Our...
Pathogenic bacteria such as Bordetella bronchiseptica modulate host immune responses to enable their establishment and persistence; however, the response is generally successful in clearing these bacteria. Here, we model dynamic outcome of interplay between components B. virulence factors. The extends our previously published interaction network includes existing experimental information on relative timing IL10 IFNγ activation form qualitative inequalities. current improves previous one two...
Abstract Eosinophils are found in the lungs of humans with allergic asthma, as well animals models this disease. Increasing evidence suggests that these cells integral to development asthma C57BL/6 mice. However, specific function eosinophils is required for event not known. In study, we experimentally validate a dynamic computational model and perform follow-up experimental observations determine mechanism eosinophil modulation T cell recruitment lung during asthma. We find deficient IL-13...
Infections with West Nile virus (WNV) are typically asymptomatic, but some patients experience severe neurological disease and even death. Over 1500 fatalities have resulted from the more than 37,000 WNV cases in USA between 1999 2012. While it is clear that age a significant risk factor, markers of immune status associated susceptibility to infections incompletely defined. We taken advantage stable characteristics individual profile stratified cohort healthy subjects history asymptomatic or...
Background Injection drug use is a growing major public health concern. users (IDUs) have higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response critical for optimal homeostasis protection from infection; however, the impact injection heroin on immunity poorly understood. We hypothesized that IDUs altered B cell antibody profiles. Methods Findings A comprehensive systems biology-based cross-sectional assessment 130 peripheral blood...
Abstract Introduction The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes severity COVID-19 disease. Additionally, is influenced by age and has more severe presentations older individuals. This raises questions about innate as a function lung development age. Method Therefore, we investigated transcriptome different cell populations epithelium using pediatric adult tissue samples from LungMAP Human Tissue Core Biorepository. Specifically, lobes were...
While durable antibody responses from long-lived plasma cell (LLPC) populations are important for protection against pathogens, LLPC may be harmful if they produce antibodies self-proteins or self-nuclear antigens as occurs in autoimmune diseases such systemic lupus erythematosus (SLE). Thus, the elimination of autoreactive improve treatment antibody-driven diseases. However, remain a challenging therapeutic target. Here, we compare matched bone marrow (BM) and peripheral blood (PBL) (PC)...
ABSTRACT Influenza viruses continue to present global threats human health. Antigenic drift and shift, genetic reassortment, cross-species transmission generate new strains with differences in epidemiology clinical severity. We compared the temporal transcriptional responses of dendritic cells (DC) infection two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response included stronger...
Gene set enrichment analyses (GSEAs) are widely used in genomic research to identify underlying biological mechanisms (defined by the gene sets), such as Ontology terms and molecular pathways. There two caveats currently available methods: (i) they typically designed for group comparisons or regression analyses, which do not utilize temporal information efficiently time-series of transcriptomics measurements; (ii) genes overlapping multiple pathways considered times hypothesis testing.We...
Objective: To determine if service members deployed to locations with open air burn pits have different serum microRNA (miRNA) profiles after deployment compared length-of-service matched, non-deployed individuals. We also tested for correlations between miRNA and levels of Polychlorinated Dibenzo-p-Dioxins/Dibenzofurans (PCDD/PCDFs). Methods: MiRNAs were isolated quantified by PCR array. Groups analyzed differences in expression. Correlations PCDD/PCDFs assessed a linear regression model....
The aim of this study was to investigate whether serum samples from the Department Defense Serum Repository (DoDSR) are sufficient quality detect microRNAs (miRNAs), cytokines, immunoglobulin E (IgE), and polycyclic aromatic hydrocarbons (PAHs).MiRNAs were isolated quantified by polymerase chain reaction (PCR) array. Cytokines chemokines related inflammation measured using multiplex immunoassays. Cotinine IgE detected enzyme-linked immunoassay (ELISA) PAHs Liquid Chromatography/Mass...