A5036341163- Antifungal resistance and susceptibility
- Microbial Natural Products and Biosynthesis
- Fungal and yeast genetics research
- Fungal Infections and Studies
- Mycotoxins in Agriculture and Food
- Fungal Biology and Applications
- Peptidase Inhibition and Analysis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Biochemical and Structural Characterization
- Signaling Pathways in Disease
- Genomics and Phylogenetic Studies
- Microbial infections and disease research
- interferon and immune responses
- Immunotherapy and Immune Responses
- Adipose Tissue and Metabolism
- Viral Infections and Immunology Research
- Antimicrobial Peptides and Activities
- Plant-Microbe Interactions and Immunity
- Immune cells in cancer
- Gout, Hyperuricemia, Uric Acid
- Plant and Fungal Interactions Research
- Cytokine Signaling Pathways and Interactions
- bioluminescence and chemiluminescence research
- Nuclear Structure and Function
Clemson University
2020-2024
Dartmouth College
2014-2023
Northern Illinois University
2009-2016
Wrexham Maelor Hospital
2006
Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development systemic insulin resistance, yet changes their energy are currently unknown. We therefore set out to study metabolic signatures (ATMs) lean obese conditions. F4/80-positive ATMs were isolated from vs mice. High-fat feeding wild-type mice...
ABSTRACT Bacillus megaterium is deep-rooted in the phylogeny, making it an evolutionarily key species and of particular importance understanding genome evolution, dynamics, plasticity bacilli. B. a commercially available, nonpathogenic host for biotechnological production several substances, including vitamin B 12 , penicillin acylase, amylases. Here, we report analysis first complete sequences two important strains, plasmidless strain DSM319 QM B1551, which harbors seven indigenous...
Fumagillin 1 is a meroterpenoid from Aspergillus fumigatus that known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. The genetic and molecular basis biosynthesis of had been an enigma despite the availability A. genome sequence. Here, we report identification verification fma gene cluster, followed characterization polyketide synthase acyltransferase involved in dioic acid portion 1. More significantly, uncovered elusive β-trans-bergamotene as...
The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance virulence. latter phenotype especially striking, as loss results in complete virulence murine models invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate unknown, though it has been suggested that lack growth hypoxic conditions accounts attenuated To further understand role...
Fumagillin (1), a meroterpenoid from Aspergillus fumigatus, is known for its antiangiogenic activity due to binding human methionine aminopeptidase 2. 1 has highly oxygenated structure containing penta-substituted cyclohexane that generated by oxidative cleavage of the bicyclic sesquiterpene β-trans-bergamotene. The chemical nature, order, and biochemical mechanism all oxygenative tailoring reactions remained enigmatic despite identification biosynthetic gene cluster use targeted-gene...
Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects myeloid function, although the mechanism of cell-mediated immune surveillance remains unclear. By monitoring fungal physiology vivo, we demonstrate that lung neutrophils trigger programmed cell death apoptosis-like features Aspergillus fumigatus conidia, most prevalent human pathogen. An antiapoptotic protein,...
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical infection establishment are known, genes essential disease persistence and progression ill defined. We propose that promote navigation the rapidly changing nutrient structural landscape characteristic represent untapped clinically relevant therapeutic targets. To this end, we find A. requires carbon catabolite repression...
ABSTRACT Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immunocompromised patients. In this study, we show that veA , major conserved regulatory gene unique to fungi, necessary for normal morphogenesis medically relevant fungus. Although deletion results strain with reduced conidiation, overexpression further conidial production, indicating has role as regulator development A. and conidiation only sustained the presence wild-type VeA...
Secondary metabolism in the model fungus Aspergillus nidulans is controlled by conserved global regulator VeA, which also governs morphological differentiation. Among secondary metabolites regulated VeA mycotoxin sterigmatocystin (ST). The presence of necessary for biosynthesis this carcinogenic compound. We identified a revertant mutant able to synthesize ST intermediates absence VeA. point mutation occurred at coding region gene encoding novel putative C2H2 zinc finger domain transcription...
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that plays critical role in regulating myeloid cell host defense. In this study, we demonstrated GM-CSF signaling an essential antifungal defense against Aspergillus fumigatus. Mice lack the receptor β chain (GM-CSFRβ) developed invasive hyphal growth and exhibited impaired survival after pulmonary challenge with A. fumigatus conidia. GM-CSFRβ regulated recruitment of inflammatory monocytes to infected lungs,...
Aspergillus fumigatus is the causative agent of invasive aspergillosis, leading to infection-related mortality in immunocompromised patients. We previously showed that conserved and unique-to-fungi veA gene affects different cell processes such as morphological development, gliotoxin biosynthesis protease activity, suggesting a global regulatory effect on genome this medically relevant fungus. In study, RNA sequencing analysis revealed controls expression hundreds genes A. fumigatus,...
Trehalose biosynthesis is found in fungi but not humans. Proteins involved trehalose are essential for fungal pathogen virulence humans and plants through multiple mechanisms. Loss of canonical genes the human Aspergillus fumigatus significantly alters cell wall structure integrity, though mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA tslB, which encode proteins that contain domains similar to those corresponding...
Abstract RIG-I–like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate IFN responses against viruses. Whether RLR family has broader effects on host immunity other pathogen families remains be fully explored. In this study, we demonstrate MDA5/MAVS signaling was essential for resistance pulmonary Aspergillus fumigatus challenge regulation of antifungal leukocyte in mice. Activation driven by dsRNA from live A. serving as a key vitality-sensing pattern...
SREBP transcription factors play a critical role in fungal virulence; however, the mechanisms of sterol regulatory element binding protein (SREBP) activation pathogenic fungi remains ill-defined. Screening Neurospora crassa whole-genome deletion collection for genes involved hypoxia responses identified gene an uncharacterized rhomboid protease homolog, rbdB, required growth under hypoxic conditions. Loss rbdB Aspergillus fumigatus also inhibited In addition, A. ΔrbdB strain displayed...
Aspergillus fumigatus is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search novel genetic targets against we studied WOPR transcription factor OsaA. The deletion osaA gene resulted colony growth reduction. Conidiation also influenced by osaA; both and overexpression a decrease spore production. Wild-type expression levels are necessary for conidiation regulatory genes brlA, abaA, wetA. addition, normal cell wall...
Summary In Aspergillus nidulans the global regulatory gene veA is necessary for biosynthesis of several secondary metabolites, including mycotoxin sterigmatocystin (ST). order to identify additional ‐dependent genetic elements involved in regulating ST production, we performed a mutagenesis on deletion (Δ ) strain obtain revertant mutants (RM) that regained capability produce toxin. Genetic analysis and molecular characterization one mutants, RM3, revealed point mutation occurred at coding...
Regulation of fungal cell wall biosynthesis is critical to maintain integrity in dynamic infection microenvironments. Genes involved this response that impact fitness and host immune responses remain be fully defined. In study, we observed a yeast
Potassium, a widely accepted macronutrient, is vital for many physiological processes such as regulation of cell volume, maintenance intracellular pH, synthesis proteins and activation enzymes in filamentous fungi. Another cation, calcium, plays an essential role signaling from lower to higher eukaryotes. Imbalance the ionic levels potassium or calcium causes adverse effects on growth, morphology development, eventually death. Previous studies adaptation Aspergillus nidulans salt osmotic...
Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing 600,000 deaths every year. Aspergillus fumigatus causes pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases human infections. Thus, the development of new clinical modalities as stand-alone adjunctive therapy for improving IPA patient outcomes critically needed. Here we tested vitro vivo impacts hyperbaric oxygen (HBO)...
In fungi, conserved homeobox-domain proteins are transcriptional regulators governing development. Aspergillus species, several transcription factor genes have been identified, among them, hbxA / hbx1 . For instance, in the opportunistic human pathogen fumigatus , is involved conidial production and germination, as well virulence secondary metabolism, including of fumigaclavines, fumiquinazolines, chaetominine. agriculturally important fungus flavus disruption results fluffy aconidial...
Abstract Purpose of Review Non-coding RNAs (ncRNAs), including regulatory small (sRNAs) and long non-coding (lncRNAs), constitute a significant part eukaryotic genomes; however, their roles in fungi are just starting to emerge. ncRNAs have been shown regulate gene expression response varying environmental conditions (like stress) chemicals, antifungal drugs. In this review, I highlighted recent studies focusing on the functional pathogenic fungi. Recent Findings Emerging evidence suggests...