A5058785577- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Cytomegalovirus and herpesvirus research
- Plant biochemistry and biosynthesis
- Cholesterol and Lipid Metabolism
- Endoplasmic Reticulum Stress and Disease
- Cancer, Lipids, and Metabolism
- Immune Cell Function and Interaction
- Congenital Diaphragmatic Hernia Studies
- HIV Research and Treatment
- Calcium signaling and nucleotide metabolism
- Neonatal Respiratory Health Research
- T-cell and B-cell Immunology
- Cellular transport and secretion
- Renal and related cancers
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Lipoproteins and Cardiovascular Health
- vaccines and immunoinformatics approaches
- Transgenic Plants and Applications
- Adenosine and Purinergic Signaling
- CRISPR and Genetic Engineering
- Nuclear Receptors and Signaling
- Cell Adhesion Molecules Research
- Lipid metabolism and biosynthesis
University of Cambridge
2013-2025
Harvard University
2023-2025
Institute for Medical Research
2018
Heidelberg University
2011
Alveolar type 2 (AT2) cells maintain lung health by acting as stem and producing pulmonary surfactant. AT2 dysfunction underlies many diseases, including interstitial disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung modeling dissection underlying mechanisms remain challenging due to complexities deriving maintaining human ex vivo. Here, we describe development mature, expandable organoids derived fetal lungs are...
Significance Newly synthesized proteins undergo a strict quality-control checkpoint, and misfolded secretory are targeted across the endoplasmic reticulum membrane back to cytosol for proteasome degradation. This process requires tagging errant with ubiquitin by an E3 ligase. In genetic screen we identified TMEM129 as novel unusual is hijacked human cytomegalovirus degrade MHC-I signaling molecules avert immune recognition of infected cell. We suggest important ligase in turnover within...
Mammalian HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol biosynthetic pathway and therapeutic target statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR ubiquitinated degraded, but identity E3 ubiquitin ligase(s) responsible for mammalian turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous reporter, we comprehensively map ligase...
Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics perform a comprehensive time course analysis of >6500 viral proteins during HIV infection. To enable specific functional predictions, we categorized regulated by according patterns temporal expression. focussed on depleted with similar kinetics APOBEC3C, found the accessory protein Vif be necessary sufficient for CUL5-dependent...
Abstract Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved LDL-cholesterol import. We characterise C18orf8 as core subunit of Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required complex stability function. -deficient lack Rab7 activation show severe defects late endosome morphology endosomal trafficking, resulting cellular deficiency....
Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed was unique downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ thrombomodulin....
Article8 March 2018Open Access Transparent process MARCH6 and TRC8 facilitate the quality control of cytosolic tail-anchored proteins Sandra Stefanovic-Barrett Department Medicine, Cambridge Institute for Medical Research, University Cambridge, UK Search more papers by this author Anna S Dickson Stephen P Burr James C Williamson Ian T Lobb Dick JH van den Boomen Paul J Lehner A Nathan Corresponding Author [email protected] orcid.org/0000-0002-0248-1632 Information Stefanovic-Barrett1,...
Misfolded MHC class I heavy chains (MHC HCs) are targeted for endoplasmic reticulum (ER)-associated degradation (ERAD) by the ubiquitin E3 ligase HRD1, and E2 conjugating enzyme UBE2J1, represent one of few known endogenous ERAD substrates. The mechanism which misfolded proteins dislocated across ER membrane into cytosol is unclear. Here, we investigate requirements ubiquitination show that HCs recognized in lumen EDEM1 a glycan-dependent manner to core SEL1L/HRD1/UBE2J1 complex. A soluble...
Activation of naïve T cells requires costimulation via TCR/CD3 plus accessory receptors, which enables the dynamic rearrangement actin cytoskeleton and immune synapse maturation. Signaling events induced following may thus be valuable targets for therapeutic immunosuppression. Phosphorylation actin-bundling protein L-plastin represents such a costimulatory signal in primary human cells. Phosphorylated has higher affinity toward F-actin. However, importance phosphorylation regulation upon...
Misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), viral US2 targets HLA class I molecules (HLA-I) for via ERAD to avoid elimination immune system. US2-mediated of HLA-I serves as paradigm has facilitated identification TRC8 (also known RNF139) an E3 ubiquitin ligase. No specific E2 enzymes had previously...
Abstract Alveolar type 2 (AT2) cells maintain lung health by acting as stem and producing pulmonary surfactant 1–3 . AT2 dysfunction underlies many diseases including interstitial disease (ILD), in which some inherited forms result from mislocalisation of protein C (SFTPC) variants 4,5 Disease modelling dissection mechanisms remains challenging due to complexities deriving maintaining ex vivo. Here, we describe the development expandable adult AT2-like organoids derived human fetal are...
Summary Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, using an endogenous cholesterol reporter a genome-wide CRISPR screen we identify >70 genes involved LDL-cholesterol import. We characterise C18orf8 as core component of Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required complex stability and function. -deficient lack Rab7 activation show severe defects late endosome morphology endosomal trafficking, resulting cellular deficiency....
ABSTRACT HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol biosynthetic pathway and therapeutic target statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR ubiquitinated degraded, but identity E3 ubiquitin ligase(s) responsible for mammalian turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous reporter, we comprehensively map ligase...