A5030021197- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Geriatric Care and Nursing Homes
- Advanced Fluorescence Microscopy Techniques
- Biosensors and Analytical Detection
- Cell Adhesion Molecules Research
- Infection Control and Ventilation
- Ethics in medical practice
- Cell Image Analysis Techniques
- Intensive Care Unit Cognitive Disorders
- Family and Patient Care in Intensive Care Units
- Invertebrate Immune Response Mechanisms
- Single-cell and spatial transcriptomics
- COVID-19 epidemiological studies
University of Bristol
2016-2022
The Francis Crick Institute
2020-2022
University College London
2006-2020
University College London Hospitals NHS Foundation Trust
2020
National Hospital for Neurology and Neurosurgery
2020
Whittington Hospital
2006
Recently developed KRAS G12C inhibitory drugs are beneficial to lung cancer patients harboring mutations, but drug resistance frequently develops. Because of the immunosuppressive nature signaling network controlled by oncogenic KRAS, these can indirectly affect antitumor immunity, providing a rationale for their combination with immune checkpoint blockade. In this study, we have characterized how inhibition reverses immunosuppression driven in number preclinical models varying levels...
Fluorescence microscopy is one of the most important tools in cell biology research because it provides spatial and temporal information to investigate regulatory systems inside cells. This technique can generate data form signal intensities at thousands positions resolved individual live However, given extensive cell-to-cell variation, these cannot be readily assembled into three- or four-dimensional maps protein concentration that compared across different cells conditions. We have...
PD-1 signaling suppresses tumor-infiltrating lymphocytes by destabilizing their interactions with target tumor cells.
Notch is a critical regulator of T cell differentiation and activated through proteolytic cleavage in response to ligand engagement. Using murine myelin-reactive CD4 cells, we demonstrate that proximal signaling modulates activation by spatiotemporally constrained mechanism. The protein kinase PKCθ mediator the antigen receptor principal costimulatory CD28. selectively inactivates negative F-actin generation, Coronin 1A, at center interface with presenting (APC). This allows for effective...
Abstract Tumors generate an immune-suppressive environment that prevents effective killing of tumor cells by CD8 + cytotoxic T (CTL). It remains largely unclear upon which cell type and at stage the anti-tumor response mediators suppression act. We have combined in vivo model with a matching vitro reconstruction microenvironment based on spheroids to identify suppressors immunity directly act interaction between CTL determine mechanisms action. An adenosine 2A receptor antagonist, as...
Abstract Recently developed KRAS G12C inhibitory drugs are beneficial to lung cancer patients harbouring mutations, but drug resistance frequently develops. Due the immunosuppressive nature of signaling network controlled by oncogenic KRAS, these can indirectly affect anti-tumour immunity, providing a rationale for their combination with immune checkpoint blockade. In this study, we have characterised how inhibition reverses suppression driven in number pre-clinical models varying levels...
Abstract CD8 + T cell killing of tumor cells is suppressed by the microenvironment. Inhibitory receptors, prominently PD-1, are key mediators this suppression. To discover cellular defects triggered exposure and associated PD-1 signaling, we have established an ex vivo imaging approach to investigate infiltrating lymphocytes (TILs) interacting with targets. Whilst TIL:tumor couples formed effectively, couple stability deteriorated within 1-2 minutes. This was excessive cofilin recruitment...
Abstract Tumors generate an immune-suppressive environment that prevents effective killing of tumor cells by CD8 + cytotoxic T (CTL). It remains largely unclear upon which cell type and at stage the anti-tumor response mediators suppression act. We have combined in vivo model with a matching vitro reconstruction microenvironment based on spheroids to identify suppressors immunity directly act interaction between CTL determine mechanisms action. An adenosine 2a receptor antagonist, as...