A5007972878- Pancreatic function and diabetes
- Diabetes Management and Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Lupus Erythematosus Research
- Viral gastroenteritis research and epidemiology
- Bacillus and Francisella bacterial research
- Probiotics and Fermented Foods
- Gut microbiota and health
- Immune Response and Inflammation
- Inflammation biomarkers and pathways
- Clostridium difficile and Clostridium perfringens research
- Coenzyme Q10 studies and effects
- Bioactive Compounds and Antitumor Agents
- Escherichia coli research studies
- High Altitude and Hypoxia
- Barrier Structure and Function Studies
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Sphingolipid Metabolism and Signaling
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
National Institutes of Health
2016-2024
The University of Texas MD Anderson Cancer Center
2018-2023
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2016-2020
University of Florida
2011-2015
Florida College
2011-2012
Cancer Genetics (United States)
2012
<h3>Objectives</h3> To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. <h3>Methods</h3> Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated biopsies obtained at time diagnosis microdissected into glomerular tubulointerstitial compartments. Microarray-derived differential 88 genes...
Objectives The presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified systemic lupus erythematosus (SLE). Because LDG PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cohort patients SLE. Methods normal-density (NDG) isolated from fresh blood healthy donors (HD) Associations...
Significance Tissues exposed to the environment are sites of exposure symbiotic microbes including fungi that continuously sensed by immune system. Here, we show immunity commensal skin can significantly aggravate tissue inflammation. Enhanced pathology caused preexposure depends on lymphocytes able produce cytokine IL-17 and formation extracellular traps neutrophils. We also found fungal prior experimental modeling psoriasis recapitulates features transcriptional landscape human lesional...
The peptidylarginine deiminases PAD2 and PAD4 are implicated in the pathogenesis of several autoimmune diseases. may be pathogenic systemic lupus erythematosus (SLE) through its role neutrophil extracellular trap (NET) formation that promotes autoantigen externalization, immune dysregulation, organ damage. this enzyme mouse models autoimmunity remains unclear, as pan-PAD chemical inhibitors improve clinical phenotype, whereas PAD4-KO have given conflicting results. SLE has not been...
The intestinal epithelium is equipped with sensing receptor mechanisms that interact luminal microorganisms and nutrients to regulate barrier function gut immune responses, thereby maintaining homeostasis. Herein, we clarify the role of extracellular calcium‐sensing (CaSR) using epithelium‐specific Casr −/− mice. Epithelial CaSR deficiency diminished function, altered microbiota composition, skewed responses towards proinflammatory. Consequently, mice were significantly more prone chemically...
A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog an antioxidant that used humans to treat diverse diseases which function impaired. This study was undertaken assess whether idebenone ameliorates murine models.Idebenone administered orally MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 idebenone-containing diet) 8 weeks. At peak...
OBJECTIVE A progressive decline in insulin responses to glucose was noted individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred prediabetic NOD mice—the prototypic model for human RESEARCH DESIGN AND METHODS Morning blood measured every other day a cohort females. Glucose tolerance and secretion were longitudinally by intraperitoneal tests NOD/ShiLtJ BALB/cJ mice 6 14 weeks age. Arginine-stimulated sensitivity assessed during arginine or tests....
Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) female NOD/ShiLtJ mice starting at 8 weeks age until onset or 26 age. Consistent with notion, majority developed (354 489 [72%]) displayed increase transient excursions...
Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at genome-wide significant AD-risk locus and its reduced expression associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia human AD patients found an enrichment PU.1-binding motifs the differentially expressed genes. In hippocampal tissues transgenic mice neurodegeneration, we vastly increased...
Background Currently, sufficient data exist to support the use of lactobacilli as candidates for development new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing protective antigen (PA) component anthrax toxin genetically fused a dendritic cell (DC)-binding peptide (DCpep) induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge. Methodology/Principal Finding In present study, investigated...
As highlighted by the development of intestinal autoinflammatory disorders when tolerance is lost, homeostatic interactions between gut microbiota, resident immune cells, and epithelium are key in maintenance gastrointestinal health. Gut responses, whether stimulatory or regulatory, dictated activated dendritic cells (DCs) that first interact with microorganisms their gene products to then elicit T B cell responses. Previously, we have demonstrated treatment genetically modified...
Mitochondria are indispensable in the life and death of many types eukaryotic cells. In pancreatic beta cells, mitochondria play an essential role secretion insulin, a hormone that regulates blood glucose levels. Unregulated is hallmark symptom diabetes. The onset Type 1 diabetes preceded by autoimmune-mediated destruction However, exact has not been assessed cell death. this study, we examine both Fas- proinflammatory cytokine-mediated human line, βLox5. IFNγ primed βLox5 cells for...
Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis. Herein, we investigated pathogenesis GI in animals orally infected with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2-) spores that resulted rapid animal death. induced significant breakdown intestinal barrier function and led to gut dysbiosis, resulting systemic dissemination not only anthracis, but also commensals. Disease progression significantly correlated deterioration innate T cell...
Ingestion of Bacillus anthracis spores causes gastrointestinal (GI) anthrax. Humoral immune responses, particularly immunoglobulin A (IgA)–secreting B-1 cells, play a critical role in the clearance GI pathogens. Here, we investigated whether B. impacts function colonic cells to establish active infection. anthrax led significant inhibition immunoglobulins (eg, IgA) and increased expression program death 1 on cells. Furthermore, infection also diminished type 2 innate lymphoid (ILC2) their...
Herein, we describe a method to purify higher buoyancy neutrophils
Abstract Background Genome‐wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) within the membrane‐spanning 4‐domains subfamily A (MS4A) gene locus are linked with protection from Alzheimer’s Disease (AD) risk, delayed age‐at‐onset, and reduced expression of MS4A4A MS4A6A in myeloid cells. Recently, protective variants MS4A region been associated increased levels soluble triggering receptor expressed on cells 2 (sTREM2). Despite these associations,...
Abstract Background RIP Kinase 1 (RIPK1) is known to regulate necroptotic cell death in response pro‐inflammatory signaling cells where apoptotic has been compromised. Aberrant RIPK1 activation implicated several neurodegenerative disorders such as Alzheimer’s disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis. Method To investigate the role of regulating microglial demyelination, we administered a highly selective CNS penetrant inhibitor C57Bl6 mice fed with cuprizone. We...