A5010521347- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune cells in cancer
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Ferroptosis and cancer prognosis
- Chemokine receptors and signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- S100 Proteins and Annexins
- Galectins and Cancer Biology
- Respiratory viral infections research
- Pneumocystis jirovecii pneumonia detection and treatment
- Advanced Biosensing Techniques and Applications
- Gene expression and cancer classification
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Antibiotic Resistance in Bacteria
- Bacterial biofilms and quorum sensing
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
Dartmouth College
2011-2025
Dartmouth Hospital
2025
University of Kentucky
2006-2024
Dartmouth Cancer Center
2022-2024
Lexington VA Health Care System
2008-2015
King's College London
2014
Dartmouth–Hitchcock Medical Center
2014
Kings Health Partners
2014
Medical Research Council
2014
Guy's Hospital
2014
The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel structurally distinct Ig inhibitory ligand, whose extracellular domain bears homology to ligand PD-L1. This molecule is designated V-domain suppressor T cell activation (VISTA). VISTA primarily expressed on hematopoietic cells, expression highly regulated myeloid antigen-presenting cells (APCs) cells. A soluble VISTA-Ig fusion...
Abstract V-domain Ig suppressor of T-cell activation (VISTA) is a novel negative checkpoint ligand that homologous to PD-L1 and suppresses activation. This study demonstrates the multiple mechanisms whereby VISTA relieves regulation by hematopoietic cells enhances protective antitumor immunity. highly expressed on myeloid Foxp3+CD4+ regulatory cells, but not tumor within microenvironment (TME). monoclonal antibody (mAb) treatment increased number tumor-specific T in periphery enhanced...
Abstract V-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator T-cell function that expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses mice. In humans, related programmed death 1 (PD-1) pathway has shown great potential clinical immunotherapy trials. Here, we report structure human and examine lymphocyte regulation cancer. predominantly compartment with...
Abstract In the past few years, field of cancer immunotherapy has made great progress and is finally starting to change way treated. We are now learning that multiple negative checkpoint regulators (NCR) restrict ability T-cell responses effectively attack tumors. Releasing these brakes through antibody blockade, first with anti-CTLA4 followed by anti-PD1 anti-PDL1, emerged as an exciting strategy for treatment. More recently, a new NCR surfaced called V-domain immunoglobulin (Ig)-containing...
Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit development of autoimmunity. Unlike all other NCRs that are expressed on activated lymphocytes, V-type immunoglobulin domain-containing suppressor activation (VISTA) is naïve cells. We report an unexpected heterogeneity within compartment in mice, where loss VISTA disrupted major quiescent subset enhanced self-reactivity. Agonistic engagement increased tolerance by promoting antigen-induced...
Tumor hypoxia is a negative prognostic factor that implicated in oncogenic signal activation, immune escape, and resistance to treatment. Identifying the mechanistic role of escape immune-checkpoint inhibitors may aid identification therapeutic targets. We others have shown V-domain Ig suppressor T-cell activation (VISTA), checkpoint regulator B7 family, highly expressed tumor microenvironment models primary human cancers. In this study, we show VISTA HIF1α activity are correlated cohort...
We provide the first evidence for a link between polyamines and biofilm levels in Yersinia pestis, causative agent of plague. Polyamine-deficient mutants Y. pestis were generated with single deletion speA or speC double mutant. The genes code biosynthetic enzymes arginine decarboxylase ornithine decarboxylase, respectively. level polyamine putrescine compared to parental speA+ speC+ strain (KIM6+) was depleted progressively, highest found DeltaspeC mutant (55% reduction), followed by...
B cell-deficient mice are susceptible to infection by Pneumocystis carinii f. sp. muris (PC). To determine whether this susceptibility is due a requirement for cells prime T cells, we compared CD4 cell responses PC in bone marrow chimeric that express MHC class II (MHCII) on all APCs (wild-type (WT) chimeras) and MHCII except (MHCII(-/-) chimeras). Although was rapidly cleared WT mice, levels remained high lacked cells. In addition, although were primed the draining lymph nodes of MHCII(-/-)...
The stringent response is a mechanism by which bacteria adapt to nutritional deficiencies through the production of guanine nucleotides ppGpp and pppGpp, produced RelA enzyme. We investigated role relA gene in ability an extracellular pathogen, Pseudomonas aeruginosa, cause infection. Strains lacking were created from prototypical laboratory strain PAO1 as well mucoid cystic fibrosis isolate 6106, lacks functional quorum-sensing systems. absence abolished pppGpp under conditions amino acid...
The role of negative checkpoint regulators (NCRs) in human health and disease cannot be overstated. V-domain Ig-containing Suppressor T-cell Activation (VISTA) is an Ig superfamily protein predominantly expressed within the hematopoietic compartment has been studied for its regulation T cell responses. findings presented this study show that, unlike all other NCRs, VISTA deficiency dramatically impacts on macrophage cytokine chemokine production, as well chemotactic response VISTA-deficient...
While naïve CD4+ T cells have historically been considered a homogenous population, recent studies provided evidence that functional heterogeneity exists within this population. Using single cell RNA sequencing (scRNAseq), we identify five transcriptionally distinct subsets emerge the positive stage in thymus: quiescence cluster (TQ), memory-like (TMEM), TCR reactive (TTCR), an IFN responsive (TIFN), and undifferentiated (TUND). Elevated expression of transcription factors KLF2, Mx1, Nur77...
Influenza virus is a significant cause of mortality and morbidity in children; however, little known about the T cell response infant lungs. Neonatal mice are highly vulnerable to influenza only control very low doses virus. We compared infection between infected as adults or at 2 d old observed defective migration into lungs neonatal mice. In adult mice, numbers cells lung interstitia peaked 10 postinfection, whereas infiltration, activation, expression TNF-alpha was delayed until wk...
Overcoming immune suppression is a major barrier to eliciting potent CD8
Pneumocystis pneumonia was first diagnosed in malnourished children and has more recently been found with upper respiratory symptoms. We previously reported that there is a significant delay the immune response newborn mice infected compared to adults (Garvy BA, Harmsen AG, Infect. Immun. 64:3987-3992, 1996, Garvy Qureshi M, J. Immunol. 165:6480-6486, 2000). This characterized by failure of neonatal lungs upregulate proinflammatory cytokines attract T cells into alveoli. Here, we report...
We previously reported that neonatal mice infected with influenza A virus (IAV) develop interstitial pneumonia characterized by reduced lung cytokine and chemokine responses. The failure of T cells to infiltrate the airways neonates correlated delayed clearance sublethal IAV infections compared adults. hypothesized negative regulators in lungs such as cytokines or regulatory (Treg) are responsible for these differences. Neonates either deficient interleukin-10 (IL-10) unresponsive...
V-domain Ig Suppressor of T cell Activation (VISTA) is a negative immune checkpoint that expressed on multiple subsets and has been characterized in cells, macrophages, myeloid-derived suppressor cells. As the only naïve VISTA contributes to maintenance quiescence tolerance. also regulates myeloid activities such as chemotaxis, differentiation, migration. In context cancer, antagonistic monoclonal antibody targeting shown aid anti-tumor immunity. Furthermore, combination therapies include...
Abstract A growing body of evidence suggests that VISTA, an immune checkpoint inhibitory receptor, plays a central role in the regulation innate immunity settings inflammatory diseases and cancer. Neutrophils are among cells have highest membrane density surface VISTA. Targeting VISTA on neutrophils with agonist antibody resulted striking reduction their LPS-induced peripheral accumulation. Fc receptor engagement was required for anti-VISTA to mediate its effects neutrophils. Concomitant...
Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality delayed clearance of the virus. Generating effective CD8
While naive CD4+ T cells have historically been considered a homogenous population, recent studies provided evidence that functional heterogeneity exists within this population. Using single cell RNA sequencing (scRNAseq), we identify five transcriptionally distinct subsets emerge the positive stage in thymus: quiescence cluster (TQ), memory-like (TMEM), TCR reactive (TTCR), an IFN responsive (TIFN), and undifferentiated (TUND). Elevated expression of transcription factors KLF2, Mx1, Nur77...