A5032820870- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Neutropenia and Cancer Infections
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Pancreatic function and diabetes
- Polyomavirus and related diseases
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Muscle Physiology and Disorders
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- Diabetes and associated disorders
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- melanin and skin pigmentation
Immunocore (United Kingdom)
2021
Cancer Research UK
2016-2020
University of Oxford
2016-2020
Medical Research Council
2016-2020
CRUK/MRC Oxford Institute for Radiation Oncology
2016-2019
Cardiff University
2006
Abstract Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate—a covalent TOP1-DNA adduct known as cleavage complex (TOP1cc)—is stabilised. TOP1ccs are highly cytotoxic failure resolve them underlies the pathology neurological disorders but exploited in cancer therapy where target widely used frontline anti-cancer drugs. A critical...
The PD-1/PD-L1 pathway is a key immune checkpoint that regulates T cell activation. There strong rationale to develop PD-1 agonists as therapeutics against autoimmunity, but progress in this area has been limited. Here, we generated receptor (TCR) targeting, agonist bispecifics called ImmTAAI molecules mimic the ability of PD-L1 facilitate colocalization with TCR complex at target cell-T interface. specifically bound cells and were highly effective activating on interacting achieve...
Abstract The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient protease exhibit DPC-induced stress genome instability, manifesting as premature ageing liver cancer. Here, we provide a body of evidence suggesting that activates the ATR-CHK1 phosphorylation signalling cascade during physiological by proteolysis-dependent eviction CHK1 from replicative chromatin. During this process, proteolyses...
Abstract The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient protease activity exhibit severe DPC-induced stress genome instability, manifesting as premature ageing liver cancer humans mice. Strikingly, SPRTN-deficient cells also show a G2/M checkpoint defect fail to activate robust kinase 1 (CHK1) signalling cascade normally triggered response stress. Here, we that activates the CHK1 during physiological...
The success of immunosuppressive therapies to preserve pancreatic islets and treat Type 1 Diabetes (T1D) has, so far, been limited either due safety concerns or lack persistent efficacy. Restricting T cell suppression the pancreas, thereby avoiding systemic immunosuppression, may overcome these issues is thus an attractive option for T1D. One possible approach inhibit destruction β-cells in T1D activate PD-1 receptor on autoreactive cells only when they enter pancreas. pathway a key immune...