A5032619799- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- RNA regulation and disease
- Immune Cell Function and Interaction
- Multiple Sclerosis Research Studies
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Immunotherapy and Biomarkers
- Pharmacological Effects of Natural Compounds
- Barrier Structure and Function Studies
- Galectins and Cancer Biology
- Macrophage Migration Inhibitory Factor
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Advanced biosensing and bioanalysis techniques
- Extracellular vesicles in disease
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
Vanderbilt University
2023-2025
Vanderbilt University Medical Center
2024
John Wiley & Sons (United States)
2024
University of Florida
2020-2023
The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells effective tumor control. Correlations between stimulator interferon genes (STING) pathway activation spontaneous cell in human cancers led us evaluate effect STING-activating nanoparticles (STANs), which are a polymersome-based platform for delivery cyclic dinucleotide STING agonist, on attendant effects antitumor function. In multiple mouse models, intravenous...
Immune checkpoint blockade (ICB) has revolutionized cancer treatment and led to complete durable responses, but only for a minority of patients. Resistance ICB can largely be attributed insufficient number and/or function antitumor CD8+ T cells in the tumor microenvironment. Neoantigen targeted vaccines activate expand cell repertoire, historically, clinical responses have been poor because immunity against peptide antigens is typically weak, resulting activation cytotoxic cells. Herein, we...
The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated moderate-to-severe side effects, and the efficacy locally drugs short-lived. Here we show that can be suppressed by a fusion protein immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting diffusion IDO-Gal3 away from injection site. In rodent models endotoxin-induced inflammation, psoriasis, periodontal disease...
The networks of transcription factors (TFs) that control intestinal-resident memory CD8 + T (T RM ) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role TF Bcl11b in cells during infection with Listeria monocytogenes using mice post-activation, conditional deletion cells. Conditional resulted increased numbers intestinal their precursors as well decreased splenic circulating precursors. Loss was part due to homing −/− precursors,...
Stimulator of interferon genes (STING) is a promising target for potentiating antitumor immunity, but multiple pharmacological barriers limit the clinical utility, efficacy, and/or safety STING agonists. Here we describe modular platform systemic administration agonists based on nanobodies engineered
Mucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1 and play role in immune responses to infections tumors. We report here that absence of the transcription factor (TF) Bcl11b mice alters predominantly MAIT17 thymus further lung, both at steady state following Salmonella infection. Transcriptomics ChIP-seq analyses show direct control TCR signaling program position BCL11B upstream essential TFs program, including RORγt, ZBTB16 (PLZF), MAF....
Antigen-specific therapies hold promise for treating autoimmune diseases such as multiple sclerosis while avoiding the deleterious side effects of systemic immune suppression due to delivering disease-specific antigen part treatment. In this study, an antigen-specific dual-sized microparticle (dMP) treatment reversed hind limb paralysis when administered in mice with advanced experimental encephalomyelitis (EAE). Treatment reduced central nervous system (CNS) cell infiltration,...
The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity therefore plays an important role in cancer immune surveillance. This has prompted widespread development STING agonists for immunotherapy, but pharmacological barriers continue to limit the clinical impact motivate drug delivery systems improve their efficacy and/or safety. To address this challenge, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted...
The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity therefore plays an important role in cancer immune surveillance. This has prompted widespread development STING agonists for immunotherapy, but pharmacological barriers continue to limit the clinical impact motivate drug delivery systems improve their efficacy and/or safety. We developed SAPCon, a STING-activating polymer–drug conjugate platform based on strain-promoted azide–alkyne cycloaddition...
It was recently found that patients with relapsing remitting multiple sclerosis exhibit widespread loss of adenosine-to-inosine (A-to-I) RNA editing, which contributes to the accumulation immunostimulatory double-stranded Alu in circulating leukocytes and an attendant increase levels proinflammatory cytokines (e.g., type I IFNs). A specific (i.e., AluJb RNA) implicated activating RNA-sensing pathways be a potent innate immune agonist. Here, we have performed bioinformatic analysis A-to-I...
RNA ligands of retinoic acid-inducible gene I (RIG-I) are a promising class oligonucleotide therapeutics with broad potential as antiviral agents, vaccine adjuvants, and cancer immunotherapies. However, their translation has been limited by major drug delivery barriers, including poor cellular uptake, nuclease degradation, an inability to access the cytosol where RIG-I is localized. Here this challenge addressed engineering nanoparticles that harness covalent conjugation 5'-triphospate...
Summary paragraph Chronic inflammation underlies the onset, progression and associated pain of numerous diseases.( 1 ) Current anti-inflammatory treatments administered systemically are with moderate-to-severe side effects, while locally drugs have short-lived efficacy, neither approach successfully modifies underlying causality disease.( 2 We report a new way to modulate by fusing enzyme indoleamine 2,3-dioxygenase (IDO) galectin-3 (Gal3). A general regulator inflammation( 3 ), IDO is...
Abstract Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration immune across BBB is influenced by scaffold protein IQ motif containing GTPase activating 2 (IQGAP2). In mice and zebrafish,...
<p><i>In vitro</i> characterization of AluJb RNA (Left Arm)/D-PDB. <b>A,</b> Agarose gel Arm) with and without various amounts D-PDB, as indicated. 1 µg RNA/lane. The TrackIt 100 bp DNA Ladder was employed. <b>B,</b> DLS analysis Alu-NPs Edited (i.e., Arm)/D-PDB at an N/P ratio 4 Inactive AluJB 4) relative to D-PDB. <b>C,</b> TEM images D-PDB NPs, Alu-NPs, Alu-NPs. Scale bars, µm. RAW-Dual (<b>D</b>) THP1-Dual...
<p>Effects of Alu-NPs on the immune profile tumor microenvironment. <b>A,</b> qPCR analysis B16.F10 tumors 6 hours after a second intratumoral injection PBS or at dose corresponding to 2 µg RNA. An unpaired <i>t</i> test was used for statistical analysis. ** represents <i>P</i> < 0.01 when comparing with PBS. <b>B</b>, Representative IVIS images demonstrating IFN activity in IFN-LUC following single 100 µL either RNA dose....
<p>Bioinformatic analysis of A-to-I RNA editing in human melanoma. <b>A</b> and <b>B,</b> Negative correlation between AEI time to death. <b>A,</b> was determined from RNA-seq data using melanoma samples patients prior onset therapy (<i>N</i> = 23). <i>Y</i>-axis is for each sample, <i>X</i>-axis survival weeks. Spearman <i>r</i> calculated, the <i>P</i> value by Gaussian approximation. As...
<p>Effects of Alu-NPs on the immune profile tumor microenvironment. <b>A,</b> qPCR analysis B16.F10 tumors 6 hours after a second intratumoral injection PBS or at dose corresponding to 2 µg RNA. An unpaired <i>t</i> test was used for statistical analysis. ** represents <i>P</i> < 0.01 when comparing with PBS. <b>B</b>, Representative IVIS images demonstrating IFN activity in IFN-LUC following single 100 µL either RNA dose....
<div><p>It was recently found that patients with relapsing remitting multiple sclerosis exhibit widespread loss of adenosine-to-inosine (A-to-I) RNA editing, which contributes to the accumulation immunostimulatory double-stranded Alu in circulating leukocytes and an attendant increase levels proinflammatory cytokines (e.g., type I IFNs). A specific (i.e., AluJb RNA) implicated activating RNA-sensing pathways be a potent innate immune agonist. Here, we have performed bioinformatic...
<p>Alu-NPs relay antitumor effects. <b>A,</b> Tumor growth curves for B16.F10 tumors treated intratumorally with 100 µL of either PBS or Alu-NPs at a 2 µg RNA dose (<i>n</i> = 4 greater per treatment group). As indicated on the graph, treatments were administered three times every 3 days. The tumor curve each group was truncated to first day in which mouse any reached study endpoint. A two-way ANOVA Sidak test used statistical analysis. *, <i>P</i>...
<p>Correlation of AEI to mutation, neoantigen, neopeptide, and cytolytic scores</p>
<p>Alu-NPs relay antitumor effects. <b>A,</b> Tumor growth curves for B16.F10 tumors treated intratumorally with 100 µL of either PBS or Alu-NPs at a 2 µg RNA dose (<i>n</i> = 4 greater per treatment group). As indicated on the graph, treatments were administered three times every 3 days. The tumor curve each group was truncated to first day in which mouse any reached study endpoint. A two-way ANOVA Sidak test used statistical analysis. *, <i>P</i>...