A5076422331- Cancer Immunotherapy and Biomarkers
- Inflammatory Bowel Disease
- CAR-T cell therapy research
- Microscopic Colitis
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Galectins and Cancer Biology
- Helicobacter pylori-related gastroenterology studies
- interferon and immune responses
- Retinal Development and Disorders
- Molecular Biology Techniques and Applications
- Immunodeficiency and Autoimmune Disorders
- Genetics and Neurodevelopmental Disorders
- Gene expression and cancer classification
- Bipolar Disorder and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adenosine and Purinergic Signaling
- Congenital heart defects research
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Retinal Diseases and Treatments
- Esophageal Cancer Research and Treatment
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Mycobacterium research and diagnosis
University of Cambridge
2014-2022
Cancer Research UK
2020-2022
Cancer Research UK Cambridge Center
2017-2020
Medical Research Council
2020
MRC Toxicology Unit
2020
Addenbrooke's Hospital
2017-2019
Cambridge School
2019
University of Pisa
2010-2014
Significance Patients with microsatellite stable (MSS) pancreatic (PDA) or colorectal cancer (CRC) do not respond to immunotherapy inhibitors of T cell checkpoints. A possible explanation is suggested by finding that cells in these tumors are coated the chemokine, CXCL12, and stimulation CXCR4, CXCL12 receptor on immune cells, suppresses directed migration mediated other chemokine receptors cells. We assessed relevance findings treating patients for seven days continuous infusion...
We have previously described a prognostic transcriptional signature in CD8 T cells that separates patients with IBD into two phenotypically distinct subgroups, termed IBD1 and IBD2. Here we sought to develop blood-based test could identify these subgroups without cell separation, thus be suitable for clinical use Crohn's disease (CD) ulcerative colitis (UC).
Significance Carcinomas resist immunotherapy because T cells are absent from nests of cancer cells. The chemokine/chemokine receptor system, which regulates the migration immune cells, is a candidate for this impaired intratumoral accumulation Cancer in human pancreatic, colorectal, and breast cancers coated with chemokine CXCL12 form covalent heterodimers keratin-19. This coating was investigated using mouse model pancreatic that replicates immunological characteristics cancer. Mouse...
Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties data diverse biological samples. Most experiments seek to identify subtle differences between samples with variable background noise, scenario poorly represented by datasets. Thus, users lack important information regarding complexities introduced...
Abnormal hippocampal neural plasticity has been implicated in behavioural abnormalities and complex neuropsychiatric conditions, including bipolar disorder (BD). However, the determinants of this alteration remain unknown. This work tests hypothesis that neurotransmitter serotonin (5-HT) is a key determinant neuroplasticity, its absence leads to maladaptive behaviour relevant for BD. Depletion brain 5-HT Tph2 mutant mice resulted reduced despair, anxiety, marked aggression lower habituation...
The transcription factor Rx1, also known as Rax, controls key properties of retinal precursors including migration behavior, proliferation, and maintenance multipotency. However, Rx1 effector genes are largely unknown.To identify controlled by in early precursors, we compared the transcriptome Xenopus embryos overexpressing to that which was knocked-down. In particular, selected 52 coherently regulated, i.e., actived gain function repressed loss experiments, or vice versa. RT-qPCR situ...
Abstract Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved cancer pathogenesis and acute myeloid leukaemia (AML), including hematopoietic regeneration-associated WNT10B AC133 bright cells, although existence specific remains unproven. We obtained evidences for rearrangement, which locus (WNT10B R ) within intron 1 (IVS1) flanked at 5′ by non-human sequences whose origin to be elucidated; it also expressed transcript variant IVS1 was mainly detected cohort...
Abstract The molecular mechanisms underlying the acquisition of retinal precursor identity are scarcely defined. Although homeobox gene Rx1 (also known as Rax) plays a major role in specifying precursors and maintaining their multipotent state, involved remain to be largely deciphered. Here, following highthroughput screen for genes regulated by Rx1, we found that this transcription factor specifies fate progenitors repressing normally activated adjacent ectodermal territories. Unexpectedly,...
<h3>Introduction</h3> The course of Crohn's disease (CD) varies substantially between affected individuals, but reliable prognostic markers are not available in clinical practice. This hinders management because patients with aggressive will be undertreated by conventional "step-up" therapy, while those indolent would exposed to the risks unnecessary immunosuppression a "top-down" approach. Previously, we have described transcriptional signature that is detectable within peripheral blood CD8...
While the role of CD8+ T cells in mediating response to cancer immunotherapy is well established, B remains more controversial (1–3). By conducting a large gene expression study immune checkpoint inhibitors (ICI), we show that pre-treatment cell genes associated with ICI independently cells. However, discovered such association can be completely explained by single ( FDCSP ) expressed outside compartment, fibroblastic reticular (FRCs), which form network facilitates interactions between...
Adaptation to environmental insults is an evolutionary mechanism essential for survival. The hippocampus participates in controlling adaptive responses stress and emotional state through the modulation of neuroplasticity events, which are dysregulated stress-related neuropsychiatric disorders. neurotransmitter serotonin (5-HT) has been proposed as a pivotal player hippocampal both normal conditions though its role remains still poorly understood. Here, we investigated impact 5-HT deficiency...
Abstract Inhibition of the chemokine receptor CXCR4 in combination with blockade PD-1/PD-L1 T cell checkpoint induces infiltration and anti-cancer responses murine human pancreatic cancer. Here we elucidate mechanism by which inhibition effects tumor immune microenvironment. In cell-based chemotaxis assays, find that CXCL12-stimulated inhibits directed migration mediated CXCR1, CXCR3, CXCR5, CXCR6, CCR2, respectively, receptors expressed all types participate an integrated responses....
Background: The course of Crohn's disease (CD) varies substantially between affected individuals, but reliable prognostic markers are not available in clinical practice. This hinders management because patients with aggressive will be undertreated by conventional “step-up” therapy, while those indolent would exposed to the risks and side-effects unnecessary immunosuppression if a “top-down” approach was indiscriminately used. Previously, we have described transcriptional signature that is...
ABSTRACT Objective We have previously described a prognostic transcriptional signature in CD8 T cells that separates inflammatory bowel disease (IBD) patients into 2 phenotypically-distinct subgroups, which we termed IBD1 and IBD2. Here sought to develop blood-based test could identify these patient subgroups without the need for cell separation, thus be suitable routine clinical use Crohn’s (CD) ulcerative colitis (UC). Design Patients with active IBD were recruited before treatment....
Introduction Tumour associated IL-6 downregulates hepatic ketogenesis and thus predisposes to metabolic stress during caloric deficiency. Stress induced glucocorticoids are immune suppressive can cause failure of cancer immunotherapy. Here, we investigate if this convergence host metabolism anti-tumour immunity offers a target for combination therapy with anti-IL-6 anti-PD-L1 antibodies. Material methods Combined antibodies (n=13) or equimolar control (n=12) were administered mice bearing...