A5081799660- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- COVID-19 Clinical Research Studies
- Epigenetics and DNA Methylation
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Respiratory viral infections research
- Microtubule and mitosis dynamics
- Influenza Virus Research Studies
- Mosquito-borne diseases and control
- Peroxisome Proliferator-Activated Receptors
- High Altitude and Hypoxia
- Physiological and biochemical adaptations
- Bacterial Genetics and Biotechnology
- Amino Acid Enzymes and Metabolism
- Bacteriophages and microbial interactions
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Caveolin-1 and cellular processes
- RNA and protein synthesis mechanisms
University of Cambridge
2020-2024
Newcastle University
2024
Massachusetts Institute of Technology
2023
ETH Zurich
2023
Cambridge School
2020
University of Dundee
2013-2016
PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification prolines on specific target proteins. Because PHD activity sensitive oxygen levels and certain byproducts tricarboxylic acid cycle, PHDs act as sensors cell's metabolic state. Here, we identify a critical molecular link between sensing cell-cycle control. We show function required centrosome duplication maturation through component Cep192. Importantly, also primary cilia...
The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead Disease 2019 (COVID-19). spike protein is largest structural component of mediates essential for infection, including with primary angiotensin-converting enzyme (ACE2) receptor. We performed two independent cell-based systematic screens determine whether there are additional proteins by which SARS-CoV-2 can interact cells. discovered...
Abstract 2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases involved in hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide mutagenesis screen for genetic determinants levels, we uncover a redox lipoylation pathway, on hydrolase ABHD11, signals changes dioxygenase...
Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important defence against SARS-CoV-2. This presentation resembles phenotype mice with VHL-deficient which Hypoxia-Inducible Factors are constitutively active, suggesting might drive cell abnormalities COVID-19.
Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen sterol production has resulted in shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) metazoans. Whether an analogous metazoan pathway exists unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), key transcription factor driving mammals, as oxygen-sensitive...
Low-oxygen conditions (hypoxia) have been associated primarily with cell-cycle arrest in dividing cells. Macrophages are typically quiescent G0 but can proliferate response to tissue signals. Here we show that hypoxia (1% oxygen tension) results reversible entry into the cell cycle macrophages. Cell progression is largely limited G0-G1/S phase transition little G2/M. This transitioning triggered by an HIF2α-directed transcriptional program. The accompanied increased expression of...
In general, prokaryotes are considered to be single-celled organisms that lack internal membrane-bound organelles. However, many bacteria produce proteinaceous microcompartments serve a similar purpose, i.e. concentrate specific enzymic reactions together or shield the wider cytoplasm from toxic metabolic intermediates. this paper, synthetic operon encoding key structural components of microcompartment was designed based on genes for Salmonella propanediol utilization (Pdu) microcompartment....
Hypoxia is an important developmental cue for multicellular organisms but it also a contributing factor several human pathologies, such as stroke, cardiovascular diseases and cancer. In cells, hypoxia activates major transcriptional program coordinated by the Inducible Factor (HIF) family. HIF can activate more than one hundred targets not all of them are activated at same time, there considerable cell type variability. this report we identified paired-like homeodomain pituitary...
PHD1 (also known as EGLN2) belongs to a family of prolyl hydroxylases (PHDs) that are involved in the control cellular response hypoxia. is also able regulate mitotic progression through regulation crucial centrosomal protein Cep192, establishing link between oxygen-sensing and cell cycle machinery. Here, we demonstrate phosphorylated by CDK2, CDK4 CDK6 at S130. This phosphorylation fluctuates with can be induced oncogenic activation. Functionally, leads increased induction hypoxia-inducible...
Summary The interactions between severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead COVID-19. spike protein is largest structural component of mediates essential for infection, including with primary ACE2 receptor. We performed two independent cell-based systematic screens determine whether there are additional proteins by which SARS-CoV-2 can interact cells. discovered in addition ACE2, expression...
BackgroundCigarette smoking has many serious negative health consequences. The relationship between and SARS-CoV-2 infection is controversial, specifically whether smokers are at increased risk of infection. We investigated the impact cigarette smoke on ACE2 isoform expression in differentiated primary human bronchial epithelial cells air-liquid-interface (ALI). assessed response to CSE therapeutics reported modulate ACE2. exposed ALI cultures extract (CSE) then infected them with...
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Clear cell renal carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation von Hippel-Lindau (
The snoMEN (snoRNA Modulator of gene ExpressioN) vector technology was developed from a human box C/D snoRNA, HBII-180C, which contains an internal sequence that can be manipulated to make it complementary RNA targets, allowing knock-down targeted genes. Here we have screened additional nucleolar snoRNAs and assessed their application for specific knock-downs improve the efficiency vectors. We identify characterise new vector, termed 47snoMEN, is derived snoRNA U47, demonstrating its use...
Abstract Macrophages play critical roles across health and disease. Low oxygen conditions (hypoxia) have been associated primarily with cell cycle arrest in cultured dividing cells. are typically quiescent G0, though yolk sac bone marrow derived macrophages frequently proliferate monocyte-derived tissue able to response signals. Here we show that hypoxia (1% tension) results reversible entry into the monocyte (MDM) mouse peritoneal macrophages. Cell progression is largely limited G1/S phase...
Successful segregation of chromosomes during mitosis requires that each sister chromatid is captured by microtubules emanating from opposite spindle poles. A multiprotein complex called the kinetochore provides an attachment site on for microtubules. We have found prolylhydroxylase PHD2 a critical regulator assembly kinetochore. hydroxylates component CENP-N P311 and essential localization to kinetochores. Either depletion PHD2, or expression hydroxylation-deficient mutant, results in loss...
Abstract 2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases DDs) involved in hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide mutagenesis screen for genetic determinants levels, we uncover a redox lipoylation pathway, on hydrolase ABHD11, signals changes DD...
Abstract Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen sterol production has resulted in shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) metazoans. Whether an analogous metazoan pathway exists unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), key transcription factor driving mammals, as...