A5075176672- Ubiquitin and proteasome pathways
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Inflammasome and immune disorders
- Research on Leishmaniasis Studies
- Muscle Physiology and Disorders
- Trypanosoma species research and implications
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Biotin and Related Studies
- Protein Kinase Regulation and GTPase Signaling
- Gaussian Processes and Bayesian Inference
- Genetic Neurodegenerative Diseases
- Immunotherapy and Immune Responses
- Anomaly Detection Techniques and Applications
- Protein Degradation and Inhibitors
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Sphingolipid Metabolism and Signaling
- Advanced Multi-Objective Optimization Algorithms
- Advanced Bandit Algorithms Research
University of Oxford
2019-2025
Discovery Institute
2021-2024
Science Oxford
2024
Target (United States)
2021
Wellcome Centre for Molecular Parasitology
2020
University of Glasgow
2020
University of York
2020
University of Leicester
2017
University of Sheffield
2015-2016
Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex is an essential innate immune signaling mechanism. To reveal how human NLRP3 assembly activation are controlled, in particular by components ubiquitin system, proximity labeling, affinity purification, RNAi screening approaches were performed. Our study provides intricate time-resolved molecular map different phases activation. Also, we show that C-terminal hydrolase 1 (UCH-L1) interacts with...
Enzymes that bind and process ubiquitin, a small 76 amino acid protein, have been recognized as pharmacological targets in oncology, immunological disorders neurodegeneration. Mass spectrometry technology has now reached the capacity to cover proteome with enough depth interrogate entire biochemical pathways including those contain DUBs E3 ligase substrates. We recently characterized breast cancer cell (MCF7) deep by detecting quantifying ~10,000 proteins, within this data set, we can detect...
The parasitic protozoan Leishmania requires proteasomal, autophagic and lysosomal proteolytic pathways to enact the extensive cellular remodelling that occurs during its life cycle. proteasome is essential for parasite proliferation, yet little known about requirement ubiquitination/deubiquitination processes in growth differentiation. Activity-based protein profiling of L. mexicana C12, C19 C65 deubiquitinating cysteine peptidases (DUBs) revealed DUB activity remains relatively constant...
Abstract Background Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance conventional chemotherapy, radiotherapy, and immunotherapy, are often deregulated in cancer. The deubiquitylating enzyme USP18 is major negative regulator IFN cascade predominant human protease that cleaves ISG15, ubiquitin-like protein tightly regulated context immunity, from its modified substrate proteins vivo. Methods In this study, using advanced proteomic...
Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient's 5-year survival rate less than 5%. The ubiquitin-specific protease 28 (USP28) has been implicated in tumourigenesis through its stabilization the oncoproteins c-MYC, c-JUN, Δp63. Here, we show that genetic inactivation Usp28-induced regression established murine LSCC lung tumours. We developed small molecule inhibits USP28...
Abstract Catabolism of galactose by Streptococcus pneumoniae alters the microbe’s metabolism from homolactic to mixed acid fermentation, and this shift is linked virulence. However, genetic basis switch unknown. Pyruvate formate lyase (PFL) a crucial enzyme for fermentation. Functional PFL requires activities two enzymes: pyruvate activating (coded pflA ) pflB ). To understand transcriptional regulation was studied. By microarray analysis Δ , differential several regulators were identified,...
Post-translational modifications such as ubiquitination are important for orchestrating the cellular transformations that occur Leishmania parasite differentiates between its main morphological forms, promastigote and amastigote. 2 E1 ubiquitin-activating (E1), 13 E2 ubiquitin-conjugating (E2), 79 E3 ubiquitin ligase (E3) 20 deubiquitinating cysteine peptidase (DUB) genes can be identified in mexicana genome but, currently, little is known about role of E1, enzymes this parasite. Bar-seq...
Abstract The ubiquitin proteasomal system is a critical regulator of muscle physiology, and impaired UPS key in many pathologies. Yet, little known about the function deubiquitinating enzymes (DUBs) cell context. We performed genetic screen to identify DUBs as potential regulators differentiation. Surprisingly, we observed that depletion ubiquitin-specific protease 18 (USP18) affected differentiation cells. USP18 first stimulated initiation. Later, during differentiation, absence expression...
KRAS is a proto-oncogene encoding small GTPase. Mutations contribute to ∼30% of human solid tumours, including lung adenocarcinoma, pancreatic, and colorectal carcinomas. Most activating mutations interfere with GTP hydrolysis, essential for its role as molecular switch, leading alterations in their environment oncogenic signalling. However, the precise signalling cascades these affect are poorly understood. Here, APEX2 proximity labelling was used profile WT, G12D, G13D, Q61H-activating...
Abstract: We define Recurrent Gaussian Processes (RGP) models, a general family of Bayesian nonparametric models with recurrent GP priors which are able to learn dynamical patterns from sequential data. Similar Neural Networks (RNNs), RGPs can have different formulations for their internal states, distinct inference methods and be extended deep structures. In such context, we propose novel RGP model whose autoregressive states latent, thereby performing representation learning...
Bayesian optimization (BO) has emerged during the last few years as an effective approach to optimizing black-box functions where direct queries of objective are expensive. In this paper we consider case access function is not possible, but information about user preferences is. Such scenarios arise in problems human modeled, such A/B tests or recommender systems. We present a new framework for scenario that call Preferential Optimization (PBO) which allows us find optimum latent can only be...
ABSTRACT Activation of the NACHT, LRR family pyrin domain containing 3 (NLRP3) inflammasome complex is an essential innate immune signalling mechanism. To reveal how human NLRP3 assembly and activation are controlled, in particular by components ubiquitin system, proximity labelling, affinity purification RNAi screening approaches were performed. Our study provides intricate time-resolved molecular map different phases activation. Also, we show that C-terminal hydrolase 1 (UCH-L1) interacts...
Abstract The deubiquitylating enzyme USP18 is a major negative regulator of the interferon (IFN) signalling cascade. IFN pathways contribute to resistance conventional chemotherapy, radiotherapy, and immunotherapy are often deregulated in cancer. predominant human protease that cleaves interferon-stimulated gene ISG15, ubiquitin-like protein tightly regulated context innate immunity, from its modified substrate proteins vivo . In this study, using advanced proteomic techniques, we have...
Summary Risk of neurodegenerative disease such as late onset Alzheimer’s is linked to aberrant ubiquitinylation and accumulation non-degraded proteins in brain cells. A glial network innate immune genes modulates inflammatory responses protein deposition. However, vulnerability differs between the sexes. Here, we show that Drosophila homologue deubiquitylase Trabid can align sex-specific aspects phenotypes with changes ubiquitylation activity. An enzymatically null flies, caused locomotion,...
Abstract Increasing interest in deubiquitinases (DUBs) and ubiquitin E3 ligases as drug targets to modulate critical molecular pathways disease is driven by the discovery of specific cellular roles these enzymes. Key this identification DUB or ligase substrates. While global ubiquitination changes upon perturbation DUB/E3 activity can be studied using mass spectrometry-based proteomic methods, datasets include indirect downstream events. To enrich for direct substrates enzymes, we have...
Abstract Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient 5-year survival rate less than 5%. The ubiquitin specific protease 28 (USP28) has been implicated in tumorigenesis through its stabilization the oncoprotein c-MYC. Here, we show that genetic inactivation Usp28 induced regression established murine LSCC lung tumors. We developed small molecule inhibits USP28 activity...