- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- Genetic Associations and Epidemiology
- Biochemical and Structural Characterization
- melanin and skin pigmentation
- Nutrition, Genetics, and Disease
- Pediatric health and respiratory diseases
- Antimicrobial Resistance in Staphylococcus
- Acne and Rosacea Treatments and Effects
- Dermatology and Skin Diseases
- Invertebrate Immune Response Mechanisms
- Single-cell and spatial transcriptomics
- Skin Protection and Aging
- Histone Deacetylase Inhibitors Research
- Psoriasis: Treatment and Pathogenesis
- Nicotinic Acetylcholine Receptors Study
- COVID-19 Impact on Reproduction
- Antibiotic Use and Resistance
- Microscopic Colitis
- Bacterial Infections and Vaccines
- Asthma and respiratory diseases
- Immune cells in cancer
- Clostridium difficile and Clostridium perfringens research
- IL-33, ST2, and ILC Pathways
Children's Hospital of Philadelphia
2024-2025
University of California, San Diego
2017-2024
Takeda (United States)
2024
University of South Carolina
2024
Office of Infectious Diseases
2023
University of Iceland
2014-2017
It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions a milestone host viral clearance, impact remnant peptide fragments from high loads not known. Here, we...
Patients with chronic inflammatory disorders such as psoriasis have an increased risk of cardiovascular disease and elevated levels LL37, a cathelicidin host defense peptide that has both antimicrobial proinflammatory properties. To explore if LL37 could contribute to the heart disease, we examined its effects on lipoprotein metabolism show enhances LDL uptake in macrophages through LDLR, SR-B1 CD36. This interaction led cytosolic cholesterol changes expression lipid genes consistent uptake....
Under homeostatic conditions the release of self-RNA from dying cells does not promote inflammation. However, following injury or inflammatory skin diseases such as psoriasis and rosacea, expression cathelicidin antimicrobial peptide LL37 breaks tolerance to self-nucleic acids triggers Here we report that enables keratinocytes macrophages recognize self-non-coding U1 RNA by facilitating binding cell surface scavenger receptors enable recognition nucleic acid pattern within cell. The...
Inhibition of HDAC8 and HDAC9 impairs keratinocyte tolerance TLR ligand stimulation, leading to cutaneous inflammation.
The airway epithelium restricts the penetration of inhaled pathogens into underlying tissue and plays a crucial role in innate immune defense against respiratory infections. whooping cough agent,
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts revealed 19 independent signals trait; however, mechanism action these loci remains to be elucidated. To molecularly characterize loci, we sought determine underlying causal variants corresponding effector genes within...
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened collection diverse staphylococcus species domestic dogs and cats for activity against MRSP. A unique strain ( S. felis C4) was isolated feline inhibited MRSP multiple gram-positive pathogens....
Cathelicidins such as the human 37-amino acid peptide (LL-37) are peptides that not only potently kill microbes but also trigger inflammation by enabling immune recognition of endogenous nucleic acids. Here, a detailed structure–function analysis LL-37 was performed to understand details this process. Alanine scanning 34-amino (LL-34) showed some variants displayed increased antimicrobial activity against Staphylococcus aureus and group A Streptococcus. In contrast, different substitutions...
Mechanical ventilation (MV) of patients can cause damage to bronchoalveolar epithelium, leading a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects MV innate immune defense system human lung. In this study, we demonstrate that cyclic stretch bronchial epithelial cell lines VA10 BCi NS 1.1 leads down-regulation cathelicidin antimicrobial peptide (CAMP) gene expression. We show treatment cells with vitamin D3 and/or 4-phenyl...
ABSTRACT A portion of the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but GWAS do not reveal causal variants, effector genes, or cell types impacted disease-associated variation. We have generated 3D genomic datasets consisting promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq integrated these data with 16 traits to physically map variants genes they likely regulate in 57 human types. These maps gene cis -regulatory...
Objective: This study aims to determine sex differences in poststroke hypertriglyceridemia (serum triglyceride levels ⩾ 200 mg/dl) and high stroke severity ischemic patients. Method: Our analyzed data from 392 males 373 females with hypertriglyceridemia. Stroke on admission was measured using the National Institute of Health Scale (NIHSS) a value ⩽7 indicating more favorable post-stroke prognosis while score >7 indicates poorer outcomes. Logistic regression models adjusted for demographic...
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts revealed 19 independent signals trait; however, mechanism action these loci remains to be elucidated. To molecularly characterize we sought determine underlying causal variants corresponding effector genes within diverse...
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts revealed 19 independent signals trait; however, mechanism action these loci remains to be elucidated. To molecularly characterize loci, we sought determine underlying causal variants corresponding effector genes within...
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts revealed 19 independent signals trait; however, mechanism action these loci remains to be elucidated. To molecularly characterize we sought determine underlying causal variants corresponding effector genes within diverse...
Cancer-associated fibroblasts (CAFs) play pivotal roles in solid tumor initiation, growth, and immune evasion. However, the optimal biomimetic modeling conditions remain elusive. In this study, we investigated effects of 2D 3D culturing on human primary CAFs integrated into a modular microenvironment (TME). Using single-nucleus RNA sequencing (snRNAseq) Proteomics’ Proximity Extension Assays, characterized CAF transcriptomic profiles cytokine levels. Remarkably, when cultured 2D, exhibited...
Abstract Neutrophils are key first responders to Clostridioides difficile infection (CDI). Excessive tissue and blood neutrophils associated with worse histopathology adverse outcomes, however their functional role during CDI remains poorly defined. Utilizing intestinal epithelial cell (IEC)-neutrophil co-cultures a pre-clinical animal model of CDI, we show that exacerbate C. -induced IEC injury. We utilized cutting-edge single-cell transcriptomics illuminate neutrophil subtypes biological...