A5070512123- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Cellular transport and secretion
- Retinal Development and Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Axon Guidance and Neuronal Signaling
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Ubiquitin and proteasome pathways
- Renal Transplantation Outcomes and Treatments
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
MRC Toxicology Unit
2022-2024
University of Cambridge
2022-2024
Medical Research Council
2022-2023
Secreted proteins fulfill a vast array of functions, including immunity, signaling, and extracellular matrix remodeling. In the trans-Golgi network, destined for constitutive secretion are sorted into post-Golgi carriers which fuse with plasma membrane. The molecular machinery involved is poorly understood. Here, we have used kinetic trafficking assays transient CRISPR-KO to study biosynthetic sorting from Golgi Depletion all canonical exocyst subunits causes cargo accumulation in carriers....
Abstract Age-associated B cells (ABC) accumulate with age and in individuals different immunological disorders, including cancer patients treated immune checkpoint blockade those inborn errors of immunity. Here, we investigate whether ABCs from conditions are similar how they impact the longitudinal level COVID-19 vaccine response. Single-cell RNA sequencing indicates that distinct aetiologies have common transcriptional profiles can be categorised according to their expression genes, such...
The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling primary human myeloma cells to identify an unprecedented number a cancer. We used novel approach prioritize immunotherapy and identified protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down short-hairpin RNA CRISPR/nuclease-dead Cas9 (dCas9), show that...
Abstract Chimeric antigen receptor (CAR) T-cell therapy is a highly effective novel treatment in haematological malignancies that has shown promise as therapeutic option multiple myeloma. However, widespread adoption of CAR myeloma been hindered by the challenge unbiased target identification and selection. As activation T-cells requires minimal on cell surface, major risk toxicity destruction healthy tissue expressing protein, i.e. on-target, off-tumour toxicity. Indeed, examination surface...
Abstract Precision medicine holds great promise to improve outcomes in cancer, including haematological malignancies. However, there are few biomarkers that influence choice of chemotherapy clinical practice. In particular, multiple myeloma requires an individualized approach as exist several active therapies, but little agreement on how and when they should be used combined. We have previously shown a transcriptomic signature can identify specific bortezomib- lenalidomide-sensitivity. gene...
Secreted proteins fulfil a vast array of different functions, including adaptive immunity, cell signalling and extracellular matrix remodelling. In the trans -Golgi network, destined for constitutive secretion are sorted into post-Golgi carriers which fuse with plasma membrane to deliver their contents space. The molecular machinery involved is poorly understood. Here, we have used kinetic trafficking assays transient CRISPR knock-outs study biosynthetic sorting route from Golgi apparatus...
Abstract Sensitive cell surface proteomics studies have shown that the number of completely tumour-specific targets for adoptive cellular immunotherapy is extremely low. Even approved CAR T-cell appear to expression in central nervous system, leading long-term neurological complications. We propose this toxicity could be significantly improved by adoption NOT-gates, which been limit activity against healthy tissue expressing a second target absent on tumour. Furthermore, approach also...
Abstract Age-associated B cells (ABCs) accumulate with age, as well in individuals a range of immunological dyscrasias. These include patients cancer treated immune checkpoint blockade and inborn errors immunity. In this study, we sought to determine whether ABCs found all these conditions are similar, they enhance or detract from the response COVID-19 vaccination. We use single cell RNA sequencing show that arising distinct aetiologies have common transcriptional profiles may be subdivided...