ORCID Profile
0000-0002-6587-1152
Current Organisation
University of Oxford
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Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7SC02103H
Abstract: Four compounds in clinical trials for anaemia treatment are potent inhibitors of the hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs), but differ in potency and how they interact with HIF at the PHD active site.
Publisher: Informa UK Limited
Date: 03-2008
DOI: 10.1128/MCB.01565-07
Publisher: Elsevier BV
Date: 06-2019
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.CCR.2013.03.013
Abstract: Nearly 90% of human melanomas contain inactivated wild-type p53, the underlying mechanisms for which are not fully understood. Here, we identify that cyclin B1/CDK1-phosphorylates iASPP, which leads to the inhibition of iASPP dimerization, promotion of iASPP monomer nuclear entry, and exposure of its p53 binding sites, leading to increased p53 inhibition. Nuclear iASPP is enriched in melanoma metastasis and associates with poor patient survival. Most wild-type p53-expressing melanoma cell lines coexpress high levels of phosphorylated nuclear iASPP, MDM2, and cyclin B1. Inhibition of MDM2 and iASPP phosphorylation with small molecules induced p53-dependent apoptosis and growth suppression. Concurrent p53 reactivation and BRAFV600E inhibition achieved additive suppression in vivo, presenting an alternative for melanoma therapy.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2018
DOI: 10.1038/S41467-018-06085-5
Abstract: Inflammatory bowel disease (IBD) are heterogenous disorders of the gastrointestinal tract caused by a spectrum of genetic and environmental factors. In mice, overlapping regions of chromosome 3 have been associated with susceptibility to IBD-like pathology, including a locus called Hiccs . However, the specific gene that controls disease susceptibility remains unknown. Here we identify a Hiccs locus gene, Alpk1 (encoding alpha kinase 1), as a potent regulator of intestinal inflammation. In response to infection with the commensal pathobiont Helicobacter hepaticus ( Hh ), Alpk1-deficient mice display exacerbated interleukin (IL)-12/IL-23 dependent colitis characterized by an enhanced Th1/interferon(IFN)-γ response. Alpk1 controls intestinal immunity via the hematopoietic system and is highly expressed by mononuclear phagocytes. In response to Hh , Alpk1 −/− macrophages produce abnormally high amounts of IL-12, but not IL-23. This study demonstrates that Alpk1 promotes intestinal homoeostasis by regulating the balance of type 1/type 17 immunity following microbial challenge.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-06-2014
Abstract: Two of the most debilitating and scientifically challenging diseases of the 21st century are cancer and neurodegeneration. Although cancer results from excessive cell growth, neurodegeneration is a consequence of excessive cell loss. Dysfunction of the same key regulators, including oncogenes and tumor suppressors, may cause both diseases. We report that LPS and IFN induce apoptosis-stimulating protein of p53 with signature sequences of ankyrin repeat-, SH3 domain-, and proline-rich region-containing protein 2 (ASPP2) transcription through a signal transducer and activator of transcription 1 (STAT1) -dependent but NF-κB RELA 65-independent pathway and that ASPP2 mediates LPS-induced apoptosis. Thus, the identified STAT1/ASPP2 pathway reveals an important function of ASPP2 in the cellular response to inflammation and infection and connects neuroinflammation to cell polarity and tumor suppression.
Publisher: Public Library of Science (PLoS)
Date: 16-09-2010
Publisher: Proceedings of the National Academy of Sciences
Date: 15-04-2013
Abstract: The ectodermal dysplasias are a group of inherited autosomal dominant syndromes associated with heterozygous mutations in the Tumor Protein p63 ( TRP63 ) gene. Here we show that, in addition to their epidermal pathology, a proportion of these patients have distinct levels of deafness. Accordingly, p63 null mouse embryos show marked cochlea abnormalities, and the transactivating isoform of p63 (TAp63) protein is normally found in the organ of Corti. TAp63 transactivates hairy and enhancer of split 5 (Hes5) and atonal homolog 1 (Atoh1), components of the Notch pathway, known to be involved in cochlear neuroepithelial development. Strikingly, p63 null mice show morphological defects of the organ of Corti, with supernumerary hair cells, as also reported for Hes5 null mice. This phenotype is related to loss of a differentiation property of TAp63 and not to loss of its proapoptotic function, because cochleas in mice lacking the critical Bcl-2 homology domain (BH-3) inducers of p53- and p63-mediated apoptosis—Puma, Noxa, or both—are normal. Collectively, these data demonstrate that TAp63, acting via the Notch pathway, is crucial for the development of the organ of Corti, providing a molecular explanation for the sensorineural deafness in ectodermal dysplasia patients with TRP63 mutations.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1053/J.GASTRO.2021.05.059
Abstract: Barrett's epithelium measurement using widely accepted Prague C&M classification is highly operator dependent. We propose a novel methodology for measuring this risk score automatically. The method also enables quantification of the area of Barrett's epithelium (BEA) and islands, which was not possible before. Furthermore, it allows 3-dimensional (3D) reconstruction of the esophageal surface, enabling interactive 3D visualization. We aimed to assess the accuracy of the proposed artificial intelligence system on both phantom and endoscopic patient data. Using advanced deep learning, a depth estimator network is used to predict endoscope camera distance from the gastric folds. By segmenting BEA and gastroesophageal junction and projecting them to the estimated mm distances, we measure C&M scores including the BEA. The derived endoscopy artificial intelligence system was tested on a purpose-built 3D printed esophagus phantom with varying BEAs and on 194 high-definition videos from 131 patients with C&M values scored by expert endoscopists. Endoscopic phantom video data demonstrated a 97.2% accuracy with a marginal ± 0.9 mm average deviation for C&M and island measurements, while for BEA we achieved 98.4% accuracy with only ±0.4 cm The proposed methodology automatically extracts Prague C&M scores with high accuracy. Quantification and 3D reconstruction of the entire Barrett's area provides new opportunities for risk stratification and assessment of therapy response.
Publisher: Elsevier BV
Date: 2020
Location: United Kingdom of Great Britain and Northern Ireland
Location: China
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Xin Lu.