A5080209756- Antifungal resistance and susceptibility
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fungal Infections and Studies
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Blood disorders and treatments
- Cancer, Hypoxia, and Metabolism
- Immune Response and Inflammation
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Asthma and respiratory diseases
- COVID-19 epidemiological studies
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Neutropenia and Cancer Infections
- Probiotics and Fermented Foods
- Antimicrobial Resistance in Staphylococcus
- Parasites and Host Interactions
- COVID-19 Clinical Research Studies
- Streptococcal Infections and Treatments
- Plant-Microbe Interactions and Immunity
- Nitric Oxide and Endothelin Effects
- Photodynamic Therapy Research Studies
- Sepsis Diagnosis and Treatment
Massachusetts General Hospital
2019-2025
University of Vermont
2018
Purpose Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients COVID-19 assist patient management. The aim this study to evaluate whether procalcitonin (PCT) outcome and bacterial superinfection infected severe syndrome coronavirus-2 (SARS-CoV-2). Methods Adult diagnosed SARS-CoV-2 by nasopharyngeal PCR who were admitted tertiary care center Boston, MA infection between...
Breast cancer remains the most common malignant disease in women worldwide. Despite advances detection and therapies, studies are still needed to understand mechanisms underlying this cancer. Cancer stem cells (CSC) play an important role tumor formation, growth, drug resistance, recurrence. Here, it is demonstrated that transcription factor RUNX1, well known as essential for hematopoietic differentiation, represses breast cell (BCSC) phenotype suppresses growth vivo. The current show BCSCs...
Neutrophils are recognized to represent significant immune cell mediators for the clearance and elimination of human-pathogenic fungal pathogen Candida . The sensing fungi by innate cells is performed, in part, through lectin receptor recognition wall components downstream cellular activation signaling components, including spleen tyrosine kinase (Syk). While essential role Syk macrophages dendritic clear, there remains uncertainty with respect its contribution neutrophils. In this study, we...
Abstract In tissues, neutrophils neutralize Candida albicans through phagocytosis and delay C. hyphae growth by deploying neutrophil extracellular traps (NETs). However, in the bloodstream, dynamic interactions between NETs are far less understood. Here, we employ a microfluidic assay measure significant increase intact blood within 3 hours after adding yeast or hyphae. We show that can be captured efficiently on NETs, thereby delaying transition to hyphal growth. higher amounts of samples...
Neutrophils are the most abundant white blood cell in body and key participants defense against fungal infections. Fungal infections occur often patients with cirrhosis associated increased 30‐day 90‐day mortality. Previous studies have shown that specific neutrophil functions abnormal cirrhosis, although extent of dysfunction is not well understood. We tested ability neutrophils from 21 hospitalized 23 healthy control to kill Candida albicans , a common pathogen cirrhosis. Using an assay,...
Neutrophils are a vital component of the innate immune system and play an essential function in recognition clearance bacterial fungal pathogens. There is great interest understanding mechanisms neutrophil dysfunction setting disease deciphering potential side effects immunomodulatory drugs on function. We developed high throughput flow cytometry-based assay for detecting changes to four canonical functions following biological or chemical triggers. Our detects phagocytosis, reactive oxygen...
Abstract Background Solid organ transplant (SOT) and stem cell (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts. Here, we measure anti-Candida activity. Methods Twenty-one SOT 19 SCT were enrolled 2–4 months posttransplant compared to 23 healthy control patients (HC). Neutrophils coincubated with Candida albicans, percentage killing swarming responses measured. Results from had decreased fungicidal capacity HC (42%, 43%, 72% for SCT, SOT, HC,...
The use of mature neutrophil (granulocyte) transfusions for the treatment neutropenic patients with invasive fungal infections (IFIs) has been focus multiple clinical trials. Despite these efforts, transfusion neutrophils resulted in limited benefit, likely owing to problems insufficient numbers and very short lifespan donor cells. In this report, we employed a system conditionally immortalized murine progenitors that are capable continuous expansion, allowing generation unlimited homogenous...
Neutrophils are the largest population of white blood cells in circulation, and their primary function is to protect body from microbes. They can release chromatin nucleus, forming characteristic web structures trap microbes, contributing antimicrobial defenses. The webs known as neutrophil extracellular traps (NETs). Importantly, neutrophils also NETs pathological conditions related rheumatic diseases, atherosclerosis, cancer, sepsis. Thus, determining concentration increasingly important...
Hyphae formation is a key step for fungal penetration into epithelial cells and escaping from macrophages or neutrophils. We found that 405 nm light-induced catalase deactivation results in the inhibition of hyphae growth Candida albicans. The treatment capable inhibiting across multiple hyphae-producing species. Metabolic studies on light-treated C. albicans reveal light strong reduction both lipid protein metabolism. A significant decrease unsaturated saturated fatty acids was detected...
Abstract An impaired neutrophil response to pathogenic fungi puts patients at risk for fungal infections with a high of morbidity and mortality. Acquired dysfunction in the setting iatrogenic immune modulators can include inhibition critical kinases such as spleen tyrosine kinase (Syk). In this study, we used an established system conditionally immortalized mouse progenitors investigate ability augment Syk-deficient function against Candida albicans TLR agonist signaling. LPS, known...
Necrotizing fasciitis is a potentially fatal soft tissue infection that requires prompt clinical suspicion, pharmacological and surgical interventions. Bacterial pathogens, such as beta-hemolytic streptococcus Staphylococcus aureus, are the main etiology of necrotizing fasciitis, however, rare cases caused by fungal Candida albicans, have been reported following trauma. Here, we present first case C. albicans an elective procedure in immunocompetent adult.
ABSTRACT Neutrophils communicate with one another and amplify their destructive power through swarming, a collective process that synchronizes the activities of multiple neutrophils against target. The sequence contributing to swarming clusters fungi has been recently uncovered. However, molecular signals controlling neutrophils’ during are just emerging. Here, we report spleen tyrosine kinase (SYK) inhibitors severely impair neutrophil responses, resulting in complete loss fungal...
Summary Recent studies have revealed that mutations in the transcription factor Runx1 are prevalent breast tumors. Yet, how loss of contributes to cancer (BCa) remains unresolved. We demonstrate for first time represses stem cell (BCSC) phenotype and consequently, functions as a tumor suppressor cancer. ectopic expression MCF10AT1 MCF10CA1a BCa cells reduces (60%) migration, invasion vivo growth mouse mammary fat pad (P<0.05). is decreased BCSCs, overexpression suppresses tumorsphere...
ABSTRACT Once perceived to be homogenous effector cells, neutrophils have since been shown exhibit population heterogeneity. Here, we established an experimental model of clonal neutrophil heterogeneity using conditionally immortalized granulocyte monocyte progenitors (GMPs) and their mature progeny. Transcriptional epigenetic profiling showed conserved genome-wide signatures transcription chromatin accessibility that were specific individual GMP clones paired progeny, suggesting clone...
<div>Abstract<p>Breast cancer remains the most common malignant disease in women worldwide. Despite advances detection and therapies, studies are still needed to understand mechanisms underlying this cancer. Cancer stem cells (CSC) play an important role tumor formation, growth, drug resistance, recurrence. Here, it is demonstrated that transcription factor RUNX1, well known as essential for hematopoietic differentiation, represses breast cell (BCSC) phenotype suppresses growth...
<p>S1. RUNX1 mRNA is decreased during breast cancer progression. S2. does not change cell proliferation. S3. represses tumor growth in mammary fat pad. S4. Gate for MCF10AT1 sorting. S5. CD24high Cells have high expression cells. S6. Loss of promotes stemness MCF10A and MCF7 S7. Overexpression MCF10CA1a cells BCSC population. S8. Zeb1 expressed at low level S9. Schematic diagram ChIP qPCR primers amplicons over ChIP-qPCR. S10. Knockdown ns stem phenotypes.</p>
<p>S1. RUNX1 mRNA is decreased during breast cancer progression. S2. does not change cell proliferation. S3. represses tumor growth in mammary fat pad. S4. Gate for MCF10AT1 sorting. S5. CD24high Cells have high expression cells. S6. Loss of promotes stemness MCF10A and MCF7 S7. Overexpression MCF10CA1a cells BCSC population. S8. Zeb1 expressed at low level S9. Schematic diagram ChIP qPCR primers amplicons over ChIP-qPCR. S10. Knockdown ns stem phenotypes.</p>
<div>Abstract<p>Breast cancer remains the most common malignant disease in women worldwide. Despite advances detection and therapies, studies are still needed to understand mechanisms underlying this cancer. Cancer stem cells (CSC) play an important role tumor formation, growth, drug resistance, recurrence. Here, it is demonstrated that transcription factor RUNX1, well known as essential for hematopoietic differentiation, represses breast cell (BCSC) phenotype suppresses growth...
Abstract Background Solid-organ (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts in peripheral blood. However, the neutrophils function against fungi has not been completely defined. In this study, we measure human anti-candida activity SOT SCT recipients. Methods patients were identified consented from September 2018 until April 2019. Healthy control (HC) primary care clinics. EDTA-anticoagulated blood was...