A5044954572- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Autophagy in Disease and Therapy
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Nanoparticle-Based Drug Delivery
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Fibroblast Growth Factor Research
- Cytokine Signaling Pathways and Interactions
- Analytical chemistry methods development
- Telomeres, Telomerase, and Senescence
- Immunodeficiency and Autoimmune Disorders
- Advanced biosensing and bioanalysis techniques
- Sulfur Compounds in Biology
- Mesenchymal stem cell research
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
Newcastle University
2016-2025
NIHR Newcastle Biomedical Research Centre
2024-2025
Immune Regulation (United Kingdom)
2023-2024
University of Newcastle Australia
2023-2024
Center for Cancer Research
2008-2023
National Institutes of Health
2006-2015
National Cancer Institute
2007-2015
National Institutes of Health Clinical Center
2011
Crystal Research (United States)
2007
National Institute of Dental and Craniofacial Research
2006-2007
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially...
The inhibitory ligand PDL1 transforms immune cells from attackers into regulators.
Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement also requires its life cycle)-derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of retinal pigment epithelium in geographic atrophy, a type age-related macular degeneration. We found NRTIs inhibit P2X7-mediated activation independent inhibition. Multiple approved clinically relevant prevented caspase-1 activation,...
Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator KLRG1+ ILC-2 function both mice humans. Increase cell numbers was attributed intrinsic defect signaling, which resulted enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion subsets...
H(2)S is an endogenous signaling molecule that may act via protein sulfhydrylation to regulate various physiological functions. also a byproduct of dietary sulfate metabolism by gut bacteria. Inflammatory bowel diseases such as ulcerative colitis are associated with increase in the colonization intestine reducing bacteria along production. Consistent its increased production, implicated mediator both genesis or maintenance. As T cells well established mediators inflammatory disease, we...
Abstract The use of bone marrow-derived mesenchymal stromal cells (BMSC) in the treatment alloimmune and autoimmune conditions has generated much interest, yet an understanding therapeutic mechanism remains elusive. We therefore explored immune modulation by a clinical-grade BMSC product model human-into-mouse xenogeneic graft-versus-host disease (x-GVHD) mediated human CD4+ Th1 cells. reversed established, lethal x-GVHD through marked inhibition cell effector function. Gene marking studies...
Immunotherapy using regulatory T cells (Treg) has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that promote the generation myeloid dendritic (DC) with reduced capacity to stimulate effector cell responses. In a model xenogeneic graft-versus-host disease (GVHD), allogeneic DC conditioned suppressed activation completely abrogated posttransplant lethality. induced programmed death ligand-1 (PD-L1) expression on...
Abstract Background CD4 + CD25 T regulatory cells (Tregs) play an important role in regulating immune responses, and influencing human diseases such as HIV infection. It has been shown that Tregs can be induced vitro by TCR stimulation of - cells. However, the mechanism remains elusive, intriguingly, similar treatment murine did not induce Foxp3 unless exogenous TGF-β was added during stimulation. Thus, we investigated possible induction engagement. We also explored effects on HIV-1...
Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost can lead serious side effects including life-threatening allergic reactions. Here, these problems overcome via the engineering supramolecular agents that manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles...
Innate lymphoid cells (ILCs) play a key role in tissue-mediated immunity and can be controlled by coreceptor signaling. Here, we define subset of ILCs that are Tbet
ABSTRACT Regulatory T cells (Tregs) are important in maintaining tolerance and key players immunity. In aging, increased Treg function along with low‐grade inflammation has been reported. This dichotomy of enhanced highlights the importance understanding biology communication patterns very old. this proof‐of‐concept study, we demonstrate that aged Tregs (85 years) do not significantly communicate CD4 + CD8 effectors when compared healthy < 66‐year‐olds. Of note was CD3 CD56 CD161 −...
Murine T cells exposed to rapamycin maintain flexibility towards Th1/Tc1 differentiation, thereby indicating that promotion of regulatory (Tregs) is conditional. The degree which might inhibit human differentiation has not been evaluated. In the presence rapamycin, cell costimulation and polarization with IL-12 or IFN-α permitted CD4+ CD8+ a phenotype; activation STAT1 STAT4 pathways essential for polarity was preserved during mTOR blockade but instead abrogated by PI3 kinase inhibition....
The thymus is a major organ that generates "natural" CD4+CD25+ T regulatory cells (Tregs). However, the detailed pathway(s) by which Tregs are developed remain mystery. CD28-/- mice have profound decrease in Tregs, but underlying molecular events largely undefined.CD4+CD25+ thymocytes from wildtype and were cultured with T-cell receptor (TCR) transforming growth factor (TGF)-beta stimulation to generate CD25+ their phenotype function studied vitro vivo.TGF-beta induced Foxp3 expression...
Abstract Objective Transforming growth factor β (TGFβ) plays a key role in the onset and resolution of autoimmune diseases chronic inflammation. The aim this study was to delineate precise function TGFβ signaling salivary gland Methods We impaired mouse glands by conditionally inactivating expression receptor type I (TGFβRI), either using mammary tumor virus–Cre mice or delivering adenoviral vector containing Cre via retrograde infusion cannulated main excretory ducts submandibular glands....
We describe a novel animal model of nonmyeloablative bone marrow transplantation (BMT) using the purine analog pentostatin. Other cohorts mice received another analog, fludarabine, which we and others have previously evaluated in murine models. pentostatin for its ability to (1) operate synergistically with cyclophosphamide induce host T cell depletion; (2) suppression, as defined by modulation cytokine secretion vitro abrogation host-versus-graft reactivity vivo; (3) constrain recovery...
Telomerase is expressed in approximately 90% of breast cancers but not normal somatic cells. The catalytic subunit telomerase, human telomerase reverse transcriptase (hTERT), a widely tumour-associated antigen against which specific cytotoxic T lymphocyte (CTL) responses have been identified. Human CD8+ CTL shown to recognise hTERT synthetic peptides an HLA-restricted manner and lyse hTERT+ tumour This study has investigated the response defined cohort primary cancer patients 3 using...