A5040118446- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Ion channel regulation and function
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Lymphocytic Leukemia Research
- Calcium signaling and nucleotide metabolism
- Pancreatic and Hepatic Oncology Research
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Cardiac electrophysiology and arrhythmias
- Acute Lymphoblastic Leukemia research
- Receptor Mechanisms and Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- CAR-T cell therapy research
- Neuroscience and Neuropharmacology Research
- Chemokine receptors and signaling
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
German Center for Neurodegenerative Diseases
2019-2024
Queen Mary University of London
2010-2022
Cancer Research UK
2021
University of Leicester
2008-2010
MRC Toxicology Unit
2008-2009
Medical Research Council
2009
University of Nottingham
2006
Farmaceutici Damor (Italy)
2003-2005
Cancers are not just masses of malignant cells but complex 'rogue' organs, to which many other recruited and can be corrupted by the transformed cells. Interactions between non-transformed create tumor microenvironment (TME). The non-malignant TME have a dynamic often tumor-promoting function at all stages carcinogenesis (Hanahan Coussens, 2012). Intercellular communication is driven network cytokines, chemokines, growth factors, inflammatory matrix remodeling enzymes against background...
Abstract Purpose: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, precise role in antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize immune HGSOC metastases. Experimental Design: Unmatched pre post-chemotherapy studied. B-cell localization assessed by immunostaining. Their cytokines chemokines measured...
Phagocytosis of microbial invaders represents a fundamental defense mechanism the innate immune system. The subsequent killing microbes is initiated by respiratory burst, in which nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generates vast amounts superoxide anion, precursor to bactericidal reactive oxygen species. Cytoplasmic pH regulation crucial because NADPH functions optimally at neutral pH, yet produces enormous quantities protons. We monitored pH(i) individual human...
Background and aimsThe presence of tertiary lymphoid structures (TLSs) may confer survival benefit to patients with pancreatic ductal adenocarcinoma (PDAC), in an otherwise immunologically inert malignancy. Yet, the precise role PDAC has not been elucidated. Here, we aim investigate structure TLSs human murine cancer.MethodsMulticolor immunofluorescence immunohistochemistry were used fully characterize (transgenic [KPC (KrasG12D, p53R172H, Pdx-1-Cre)] orthotopic) cancer. An orthotopic model...
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells early disease stages remain ill defined. Chronic obstructive pulmonary (COPD) a major respiratory characterized by small-airway inflammation, emphysema, breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased early-stage COPD, molecular functional neutrophil states correlate with...
Significance B lymphocytes are crucial cells in immune responses. Their activity is regulated by signaling pathways involving reactive oxygen species (ROS). Voltage-gated proton channels modulate B-cell responses facilitating production of ROS. Here we compare the full-length channel HVCN1 L with a shorter protein isoform, S , which lacks first 20 amino acids. Cells display enhanced currents upon stimulation. In addition, internalized to lesser extent interactions receptor, resulting greater...
B cells are salient features of pancreatic ductal adenocarcinoma (PDAC) tumors, yet their role in this disease remains controversial. Murine studies have indicated a protumoral for cells, whereas clinical data show tumor-infiltrating positive prognostic factor, both PDAC and other cancers. This disparity needs to be clarified order develop effective immunotherapies. In study, we provide new evidence that reconcile human mouse highlight the importance using relevant preclinical tumor models...
Significance Brain cancer is one of the deadliest human tumors and characterized by several genetic changes leading to impairment tumor suppressive pathways oncogene activation. These alterations promote subsequent molecular changes, including modifications cellular metabolism, which are believed contribute pathogenesis. Conversely, role metabolic in regulation genomic stability brain has not been investigated. Our work shows that mitochondrial metabolism loss p53 suppressor transformation...
Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR complex 1 signaling controlling translation, as well protein levels of mediators. Genetic ablation showed a dual yet contrasting effect on priming: it caused an NF-κB–dependent upregulation priming genes at mRNA level; however, displayed reduced cytokine levels, diminished activation, milder...
Decay-accelerating factor (CD55) is a complement regulatory protein, which expressed by most cells to protect them from complement-mediated attack. CD55 also binds CD97, an EGF-TM7 receptor constitutively on granulocytes and monocytes rapidly up-regulated T B upon activation. Early results suggested that could further enhance cell proliferation induced phorbol ester treatment. The present study demonstrates coengagement of CD55, using either cross-linking mAbs or its natural ligand CD3 in...
Voltage-gated proton channels and NADPH oxidase function cooperatively in phagocytes during the respiratory burst, when reactive oxygen species are produced to kill microbial invaders. Agents that activate also enhance channel gating profoundly, facilitating its roles charge compensation pH(i) regulation. The "enhanced mode" appears reflect protein kinase C (PKC) phosphorylation. Here we examine two candidates for PKC-delta phosphorylation sites human voltage-gated channel, H(V)1 (Hvcn1),...
B cell lymphoma-6 (BCL6) is highly expressed in germinal center cells, but how its expression maintained still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) a co-chaperone of heat shock 90. Deletion Aip cells decreased BCL6 expression, reducing and diminishing adaptive immune responses. AIP was required for optimal AKT signaling response to stimulation, protected from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 binding...
Protective immunity relies upon differentiation of T cells into the appropriate subtype required to clear infections and efficient effector cell localization antigen-rich tissue. Recent studies have highlighted role played by subpopulations tissue-resident memory (TRM) lymphocytes in protection from invading pathogens. The intestinal mucosa associated lymphoid tissue are densely populated a variety resident lymphocyte populations, including αβ γδ CD8+ intraepithelial (IELs) CD4+ cells. While...
Voltage-gated hydrogen channel 1 (Hvcn1) is a voltage-gated proton channel, which reduces cytosol acidification and facilitates the production of ROS. The increased expression this in some cancers has led to proposing Hvcn1 antagonists as potential therapeutics. While its role most leukocytes been studied depth, function T cells remains poorly defined. We show that plays nonredundant protecting naive from intracellular during priming. Despite sharing overall functional impairment vivo vitro,...