A5015082475- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Digestive system and related health
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Spondyloarthritis Studies and Treatments
- Rheumatoid Arthritis Research and Therapies
- Forensic Anthropology and Bioarchaeology Studies
- Pleistocene-Era Hominins and Archaeology
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Archaeology and ancient environmental studies
- interferon and immune responses
- Mosquito-borne diseases and control
- Mitochondrial Function and Pathology
- Mass Spectrometry Techniques and Applications
- Forensic and Genetic Research
University of Oxford
2016-2025
Science Oxford
2022-2024
Discovery Institute
2016-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2021-2023
Molecular Oncology (United States)
2023
Behörde für Gesundheit und Verbraucherschutz
2023
Academy of Medical Sciences
2022-2023
Centre for Biomedical Network Research on Rare Diseases
2022
Hospital de Sant Pau
2022
Universitat Autònoma de Barcelona
2022
The Krebs cycle enzyme fumarate hydratase (FH) is a human tumor suppressor whose inactivation associated with the development of leiomyomata, renal cysts, and tumors. It has been proposed that activation hypoxia inducible factor (HIF) by fumarate-mediated inhibition HIF prolyl hydroxylases drives oncogenesis. Using mouse model, we provide genetic evidence Fh1-associated cyst formation Hif independent, as striking upregulation antioxidant signaling pathways revealed gene expression profiling....
Significance The displacement of Neandertals by anatomically modern humans (AMHs) 50,000–40,000 y ago in Europe has considerable biological and behavioral implications. Châtelperronian at the Grotte du Renne (France) takes a central role models explaining transition, but association hominin fossils this site with is debated. Here we identify additional specimens through proteomic zooarchaeology mass spectrometry screening obtain molecular (ancient DNA, ancient proteins) chronometric data to...
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire,...
Abstract Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels insulin. The molecular mechanisms underlying progressive failure respond glucose in type-2 diabetes remain unresolved. Using combination transcriptomics and proteomics, we find significant dysregulation major metabolic pathways islets diabetic βV59M mice, non-obese, eulipidaemic model. Multiple genes/proteins involved glycolysis/gluconeogenesis are upregulated,...
Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, subsequent vitro studies suggest distinct catalytic properties variants. To understand structure-activity relationships this we determined crystal structures...
Proteins persist longer in the fossil record than DNA, but longevity, survival mechanisms and substrates remain contested. Here, we demonstrate role of mineral binding preserving protein sequence ostrich (Struthionidae) eggshell, including from palaeontological sites Laetoli (3.8 Ma) Olduvai Gorge (1.3 Tanzania. By tracking diagenesis back time find consistent patterns preservation, demonstrating authenticity surviving sequences. Molecular dynamics simulations struthiocalcin-1 -2, dominant...
The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their ability block the progression DNA replication. DPCs frequently occur in cells, either as a consequence metabolism or exogenous agents, but mechanism DPC repair not completely understood. Here, we characterize SPRTN specialized DNA-dependent and replication-coupled metalloprotease for repair. cleaves various binding substrates during S-phase thus protects proliferative cells from toxicity. Ruijs-Aalfs syndrome...
Abstract Milk is a major food of global economic importance and its consumption regarded as classic example gene-culture evolution. Humans have exploited animal milk resource for at least 8500 years, but the origins, spread scale dairying remain poorly understood. Indirect lines evidence, such lipid isotopic ratios pottery residues, faunal mortality profiles lactase persistence allele frequencies, provide partial picture this process; however, in order to understand how, where when humans...
Classical activation of macrophages (M(LPS+IFNγ)) elicits the expression inducible nitric oxide synthase (iNOS), generating large amounts NO and inhibiting mitochondrial respiration. Upregulation glycolysis a disrupted tricarboxylic acid (TCA) cycle underpin this switch to pro-inflammatory phenotype. We show that NOS cofactor tetrahydrobiopterin (BH4) modulates IL-1β production key aspects metabolic remodeling in activated murine via production. Using two complementary genetic models, we...
Ion mobility can add a dimension to LC-MS based shotgun proteomics which has the potential boost proteome coverage, quantification accuracy and dynamic range. Required for this is suitable software that extracts information contained in four-dimensional (4D) data space spanned by m/z, retention time, ion signal intensity. Here we describe enhanced MaxQuant software, utilizes added dimension. It offers an end computational workflow identification of peptides proteins LC-IMS-MS/MS data. We...
Supramolecular attack particles Cytotoxic T cells (CTLs) are at the front lines against cancer and chronic infection. kill by secreting caspase-activating granzymes pore-forming protein perforin from dense core granules. However, structural basis of lethal hit delivery has remained unknown. Balint et al. enriched synaptic output CTLs to investigate released form granzyme B. They found that in stable called supramolecular complexes or SMAPs. The SMAPs were composed a shell structure assembled...
Tissue-thin parchment made it possible to produce the first pocket Bibles: Thousands were in 13th century. The source of this parchment, often called "uterine vellum," has been a long-standing controversy codicology. Use Latin term abortivum many sources led some scholars suggest that skin fetal calves or sheep was used. Others have argued would not be sustain herds if so Bibles produced from skins, arguing instead for unexpected alternatives, such as rabbit. Here, we report simple and...
Citrullination of proteins, a post-translational conversion arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented cancer. Here we show that citrullination the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) essential for growth liver metastases from colorectal (CRC). Using proteomics, demonstrate exhibit higher levels and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance...
The gene encoding the Krebs cycle enzyme fumarate hydratase (FH) is mutated in hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity causes accumulation intracellular fumarate, which can directly modify cysteine residues to form 2-succinocysteine through succination. We undertook a proteomic-based screen cells cysts from Fh1 (murine FH)-deficient mice identified 94 protein succination targets. Notably, we three mitochondrial Aconitase2 (ACO2) crucial for iron-sulfur...
Archaeological dental calculus has emerged as a rich source of ancient biomolecules, including proteins. Previous analyses proteins extracted from revealed the presence dietary milk protein β-lactoglobulin, providing direct evidence dairy consumption in archaeological record. However, potential for to preserve other food-related not yet been systematically explored. Here we analyse shotgun metaproteomic data 100 samples ranging Iron Age post-medieval period (eighth century BC nineteenth AD)...
Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems to achieve remains very poorly understood. Here, we discover the histone H2AK119 E3 ubiquitin ligase activity of repressive complex 1 (PRC1) is defined by composition its catalytic subunits and highly regulated RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping...