A5045705588- Diabetes and associated disorders
- Streptococcal Infections and Treatments
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Antimicrobial Resistance in Staphylococcus
- Infections and bacterial resistance
- Neonatal and Maternal Infections
- Burkholderia infections and melioidosis
- T-cell and B-cell Immunology
- Infective Endocarditis Diagnosis and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Galectins and Cancer Biology
- Bacterial Identification and Susceptibility Testing
- Brucella: diagnosis, epidemiology, treatment
- Wound Healing and Treatments
West Virginia University
2016-2024
Center for Rheumatology
2021-2024
Vanderbilt University Medical Center
2020-2023
Vanderbilt University
2020
Introduction Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer associated with an immunosuppressive environment. Neutrophil extracellular traps (NETs) were initially described in the context of infection but have more recently been implicated contributing to tolerogenic immune response PDAC. Thus, NETs are attractive target for new therapeutic strategies. Group A Streptococcus (GAS) has developed defensive strategies inhibit NETs. Methods In present work, we propose utilizing...
The streptococcal collagen-like proteins 1 and 2 (Scl1 Scl2) are major surface adhesins that ubiquitous among group A Streptococcus (GAS). Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i) an IS1548 element insertion promoter region (ii) a nonsense mutation within coding sequence. transcript is drastically reduced GAS, contrasting with high transcription level of allele invasive M1-type GAS. This leads to lack Scl1 expression M3 strains. In...
Keratinized epidermis constitutes a powerful barrier of the mucosa and skin, effectively preventing bacterial invasion, unless it is wounded no longer protective. Wound healing involves deposition distinct extracellular matrix (ECM) proteins enriched in cellular fibronectin (cFn) isoforms containing extra domain A (EDA). The streptococcal collagen-like protein 1 (Scl1) surface adhesin group Streptococcus (GAS), which contains an N-terminal variable (V) C-terminally located domain. During...
Summary The human‐adapted pathogen group A Streptococcus (GAS) utilizes wounds as portals of entry into host tissue, wherein surface adhesins interact with the extracellular matrix, enabling bacterial colonization. streptococcal collagen‐like protein 1 (Scl1) is a major adhesin GAS that selectively binds to two fibronectin type III (FnIII) repeats within cellular fibronectin, specifically alternatively spliced extra domains and B, FnIII tenascin‐C. Binding was mediated through conserved...
High-affinity islet autoantibodies predict type 1 diabetes in mice and humans implicate germinal centers (GCs) pathogenesis. T follicular helper (Tfh) cells are increased diabetic individuals alterations Tfh-like the peripheral blood predicted individual responses to abatacept. Tfh support GC depend on transcriptional repressor BCL6 for their maturation. We therefore hypothesized that CD4-driven deletion of Bcl6 would disrupt essential T-B lymphocyte interactions GCs prevent diabetes. To...
Signaling lymphocytic activation molecule-associated protein (SAP), a critical intracellular signaling molecule for T-B lymphocyte interactions, drives T follicular helper (Tfh) cell development in germinal centers (GCs). High-affinity islet autoantibodies predict type 1 diabetes (T1D) but do not cause β destruction. This paradox intimates Tfh cells as key pathologic effectors, consistent with an observed signature T1D. To understand how fully developed (GC Tfh) contribute to different...
Burkholderia pseudomallei is an infectious bacterium of clinical and biodefense concern, the causative agent melioidosis. The mortality rate can reach up to 50% affects 165,000 people per year; however, there currently no vaccine available. In this study, we examine antigen-specific immune response a formulated with antigens derived from outer membrane protein in B. pseudomallei, Bucl8. Here, employed number bioinformatic tools predict Bucl8-derived epitopes that are non-allergenic...
Bacterial efflux pumps are an important pathogenicity trait because they extrude a variety of xenobiotics. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) the hazardous pathogens pseudomallei and mallei . We hypothesize that Bucl8, which contains two predicted tandem outer membrane pump domains, is component putative pump. Unique to as compared other proteins, presence extended extracellular region containing (CL) domain non-collagenous C-terminus...
Abstract Bacterial efflux pumps are an important pathogenicity trait because they extrude a variety of xenobiotics. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) the Tier one select agents pseudomallei and mallei . We hypothesize that Bucl8, which contains two predicted tandem outer membrane pump domains, is component putative pump. Unique to as compared other proteins, presence extended extracellular region containing (CL) domain non-collagenous...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer associated with an immunosuppressive environment. Neutrophil extracellular traps (NETs) were initially described in the context of infection but have more recently been implicated contributing to tolerogenic immune response PDAC. Thus, NETs are attractive target for new therapeutic strategies. Group A Streptococcus (GAS) has developed defensive strategies inhibit NETs. In present work, we propose utilizing intra-tumoral GAS injection...
Islet autoantibodies, including those directed at insulin, predict type 1 diabetes (T1D) in mice and humans signal immune tolerance breach by B lymphocytes. High-affinity insulin autoantibodies T follicular helper cell involvement implicate germinal centers (GCs) T1D. The VH125SD BCR transgenic model, which 1-2% of peripheral lymphocytes recognize enables direct study insulin-binding cells. Our prior studies showed that anti-insulin receptor transgene site-directed to H chain locus fail...
<p dir="ltr">High-affinity islet autoantibodies predict type 1 diabetes in mice and humans implicate germinal centers (GCs) pathogenesis. T follicular helper (Tfh) cells are increased diabetic individuals alterations Tfh-like the peripheral blood predicted individual responses to abatacept. Tfh support GC depend on transcriptional repressor BCL6 for their maturation. We therefore hypothesized that CD4-driven deletion of <i>Bcl6</i> would disrupt essential T-B lymphocyte...
<p dir="ltr">High-affinity islet autoantibodies predict type 1 diabetes in mice and humans implicate germinal centers (GCs) pathogenesis. T follicular helper (Tfh) cells are increased diabetic individuals alterations Tfh-like the peripheral blood predicted individual responses to abatacept. Tfh support GC depend on transcriptional repressor BCL6 for their maturation. We therefore hypothesized that CD4-driven deletion of <i>Bcl6</i> would disrupt essential T-B lymphocyte...
Abstract Anti-insulin B lymphocytes (AIBCs) are key drivers of the autoimmune attack in type 1 diabetes (T1D) but their exact functions T1D pathogenesis, and point(s) during development where tolerance is lost, unknown. In class-switch-competent anti-insulin cell receptor transgenic non-obese diabetic (VH125SD.NOD) mice, 1–2% insulin-specific, which accelerates despite limited insulin autoantibody (IAA) production. Here we used VH125SD.NOD mice to determine immune lost throughout AIBC...
Abstract Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing beta cells. An essential role for B lymphocytes in the process and molecular signatures follicular helper cells (Tfhs) T1D point to importance T-B lymphocyte interactions pathological process. To understand mechanisms that underpin these interactions, we introduced deficiency signaling activation (SLAM)-associated protein (SAP) into VH125SD.NOD mice. In mice a targeted...