- 作 者: ( "shengwu liu" OR "sheng-wu liu" )
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Genome-wide survival study identifies PARL as a novel locus for clinical progression and neurodegeneration in Alzheimer’s diseaseBiological Psychiatry (IF 12.81) Pub Date : 2023-03-03 ,DOI:10.1016/j.biopsych.2023.02.992Shi-Dong Chen, Wei Zhang, Yi-Wei Feng, Bang-Sheng Wu, Liu Yang, Ya-Ru Zhang, Hui-Fu Wang, Yu Guo, Yue-Ting Deng, Jian-Feng Feng, Wei Cheng, Qiang Dong, Jin-Tai YuBackground Variability exists in trajectories of Alzheimer’s disease (AD). We aimed to identify genetic modulators of clinical progression in AD. Methods We conducted the first genome-wide survival study on AD using a two-stage approach. The discovery and replication stage separately included 1,158 and 211,817 non-demented individuals from Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the ...
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Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participantsTranslational Psychiatry (IF 7.989) Pub Date : 2022-12-14 ,DOI:10.1038/s41398-022-02278-1Si-Jia Chen, Yue-Ting Deng, Yu-Zhu Li, Ya-Ru Zhang, Wei Zhang, Shi-Dong Chen, Bang-Sheng Wu, Liu Yang, Qiang Dong, Jianfeng Feng, Wei Cheng, Jin-Tai Yu
Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some
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Prioritization of drug targets for neurodegenerative diseases by integrating genetic and proteomic data from brain and bloodBiological Psychiatry (IF 12.81) Pub Date : 2022-11-09 ,DOI:10.1016/j.biopsych.2022.11.002Yi-Jun Ge, Ya-Nan Ou, Yue-Ting Deng, Bang-Sheng Wu, Liu Yang, Ya-Ru Zhang, Shi-Dong Chen, Yu-Yuan Huang, Qiang Dong, Lan Tan, Jin-Tai YuBackground Neurodegenerative diseases are among the most prevalent and devastating neurological disorders, with few effective prevention and treatment strategies. We aimed to integrate genetic and proteomic data to prioritize drug targets for neurodegenerative diseases. Methods We screened human proteomes through Mendelian randomization to identify causal mediators of Alzheimer’s disease (AD), Parkinson’s ...
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Mobocertinib in non-small cell lung cancer.Drugs of Today Pub Date : 2022-11-01 ,DOI:10.1358/dot.2022.58.11.3408816Shengwu Liu,Kristen E LowderTyrosine kinase inhibitors (TKIs) have provided great benefit for patients with EGFR-mutant non-small cell lung cancer (NSCLC). While prior TKIs have demonstrated limited efficacy against exon 20 insertion mutations of EGFR (EGFR Ex20Ins), mobocertinib (TAK-788) is designed to specifically inhibit these Ex20Ins mutations. In a phase I/II clinical trial, mobocertinib demonstrated meaningful benefits ...
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Targeting HER2 Exon 20 Insertion-Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor MobocertinibCancer Research (IF 13.312) Pub Date : 2021-10-15 ,DOI:10.1158/0008-5472.can-21-1526Han Han, Shuai Li, Ting Chen, Michael Fitzgerald, Shengwu Liu, Chengwei Peng, Kwan Ho Tang, Shougen Cao, Johara Chouitar, Jiansheng Wu, David Peng, Jiehui Deng, Zhendong Gao, Theresa E. Baker, Fei Li, Hua Zhang, Yuanwang Pan, Hailin Ding, Hai Hu, Val Pyon, Cassandra Thakurdin, Eleni Papadopoulos, Sittinon Tang, Francois Gonzalvez, Haiquan Chen, Victor M. Rivera, Rachael Brake, Sylvie Vincent, Kwok-Kin
No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 ( HER2/ERBB2 ) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion–mutant lung cancer is still unclear. Here we
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Abstract LB002: Mechanisms of acquired resistance to KRAS G12C inhibition in cancerCancer Research (IF 13.312) Pub Date : 2021-07-01 ,DOI:10.1158/1538-7445.am2021-lb002Mark Awad,Shengwu Liu,Kathryn Arbour,Viola Zhu,Melissa Johnson,Rebecca Heist,Tejas Patil,Gregory Riely,Joseph Jacobson,Julien Dilly,Xiaoping Yang,Nicole Persky,David Root,Lynette Sholl,Lee Lim,Kavita Garg,Mark Li,Lars Engstrom,Laura Waters,J. David Lawson,Peter Olson,James Christensen,Piro Lito,Sai-Hong Inatius Ou,Pasi Janne,Andrew AguirreAbstract Background: KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRASG12C) occur in ~13% of non-small cell lung cancers (NSCLC), ~3% of colorectal cancers (CRC), and less commonly in other cancer types. In early phase clinical trials of patients with KRASG12C-mutant cancers, promising antitumor activity has been reported with drugs such as adagrasib (MRTX849) and sotorasib (AMG510) ...
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Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung CancerCancer Discovery (IF 38.272) Pub Date : 2021-07-01 ,DOI:10.1158/2159-8290.cd-20-1683Feng Li, Matthew T. Greenfield, Stephan G. Zech, Biplab Das, Narayana I. Narasimhan, Tim Clackson, David Dalgarno, William C. Shakespeare, Michael Fitzgerald, Johara Chouitar, Robert J. Griffin, Shengwu Liu, Kwok-kin Wong, Xiaotian Zhu, Victor M. RiveraMost EGFR exon 20 insertion ( EGFR ex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR -mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating EGFR ex20ins ...
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Acquired Resistance to KRASG12C Inhibition in CancerThe New England Journal of Medicine (IF 176.079) Pub Date : 2021-06-24 ,DOI:10.1056/nejmoa2105281Mark M. Awad, Shengwu Liu, Igor I. Rybkin, Kathryn C. Arbour, Julien Dilly, Viola W. Zhu, Melissa L. Johnson, Rebecca S. Heist, Tejas Patil, Gregory J. Riely, Joseph O. Jacobson, Xiaoping Yang, Nicole S. Persky, David E. Root, Kristen E. Lowder, Hanrong Feng, Shannon S. Zhang, Kevin M. Haigis, Yin P. Hung, Lynette M. Sholl, Brian M. Wolpin, Julie Wiese, Jason Christiansen, Jessica Lee, Alexa B. SchrockNew England Journal of Medicine, Volume 384, Issue 25, Page 2382-2393, June 2021. ...
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Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer.Cancer Discovery (IF 38.272) Pub Date : 2021-02-25 ,DOI:10.1158/2159-8290.cd-20-1683Huang,Yongbo Hu,Feng Li,Matthew T Greenfield,Stephan G Zech,Biplab Das,Narayana I Narasimhan,Tim Clackson,David Dalgarno,William C Shakespeare,Michael Fitzgerald,Johara Chouitar,Robert J Griffin,Shengwu Liu,Kwok-Kin Wong,Xiaotian Zhu,Victor M RiveraMost epidermal growth factor receptor (EGFR) exon 20 insertion (EGFRex20ins) driver mutations in non-small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKIs). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing ...
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Use of Ex Vivo Patient-Derived Tumor Organotypic Spheroids to Identify Combination Therapies for HER2 Mutant Non-Small Cell Lung Cancer.Clinical Cancer Research (IF 13.801) Pub Date : 2020-02-07 ,DOI:10.1158/1078-0432.ccr-19-1844Elena Ivanova,Mari Kuraguchi,Man Xu,Andrew J Portell,Luke Taus,Irmina Diala,Alshad S Lalani,Jihyun Choi,Emily S Chambers,Shuai Li,Shengwu Liu,Ting Chen,Thanh U Barbie,Geoffrey R Oxnard,Jacob J Haworth,Kwok-Kin Wong,Suzanne E Dahlberg,Amir A Aref,David A Barbie,Magda Bahcall,Cloud P Paweletz,Pasi A JännePURPOSE Evaluating drug responses using primary patient-derived cells ex vivo represents a potentially rapid and efficient approach to screening for new treatment approaches. Here, we sought to identify neratinib combinations in HER2 mutant non-small cell lung cancer (NSCLC) patient xenograft-derived organotypic spheroids (XDOTS) using a short-term ex vivo system. EXPERIMENTAL DESIGN We generated two ...
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Chemical profiling of Callicarpa nudiflora and its effective compounds identification by compound-target network analysis.Journal of Pharmaceutical and Biomedical Analysis (IF 3.571) Pub Date : 2020-01-15 ,DOI:10.1016/j.jpba.2020.113110Yong-Sheng Wu,Liu Shi,Xin-Guang Liu,Wei Li,Rui Wang,Sheng Huang,Yi Li,Dong-Lan Yan,Hui-Ying Wang,Yuan Tian,Yan-Ming Chen,Hua YangCallicarpa nudiflora, belonging to the family Verbenaceae, is widely used to treat inflammation caused by bacterial infection.However, the underlying active substances of C. nudiflora against inflammation remains obscure. In this work, an ultra high-performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight mass spectrometry method was developed to characterize the ingredients ...
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BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non–Small Cell Lung CancerCancer Immunology Research (IF 12.02) Pub Date : 2018-10-01 ,DOI:10.1158/2326-6066.cir-18-0077Dennis O. Adeegbe, Shengwu Liu, Maureen M. Hattersley, Michaela Bowden, Chensheng W. Zhou, Shuai Li, Raven Vlahos, Michael Grondine, Igor Dolgalev, Elena V. Ivanova, Max M. Quinn, Peng Gao, Peter S. Hammerman, James E. Bradner, J. Alan Diehl, Anil K. Rustgi, Adam J. Bass, Aristotelis Tsirigos, Gordon J. Freeman, Huawei Chen, Kwok-Kin Wong
KRAS mutation is present in approximately 30% of human lung adenocarcinomas. Although recent advances in targeted therapy have shown great promise, effective targeting of KRAS remains elusive, and concurrent alterations in tumor suppressors render KRAS-mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS-mutant tumors are immunosuppressive mechanisms,
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Assessing Therapeutic Efficacy of MEK Inhibition in a KRASG12C-Driven Mouse Model of Lung Cancer.Clinical Cancer Research (IF 13.801) Pub Date : 2018-06-26 ,DOI:10.1158/1078-0432.ccr-17-3438Shuai Li,Shengwu Liu,Jiehui Deng,Esra A Akbay,Josephine Hai,Chiara Ambrogio,Long Zhang,Fangyu Zhou,Russell W Jenkins,Dennis O Adeegbe,Peng Gao,Xiaoen Wang,Cloud P Paweletz,Grit S Herter-Sprie,Ting Chen,Laura Gutiérrez-Quiceno,Yanxi Zhang,Ashley A Merlino,Max M Quinn,Yu Zeng,Xiaoting Yu,Yuting Liu,Lichao Fan,Andrew J Aguirre,David A Barbie,Xianghua Yi,Kwok-Kin Wong
Purpose: Despite the challenge to directly target mutant KRAS due to its high GTP affinity, some agents are under development against downstream signaling pathways, such as MEK inhibitors. However, it remains controversial whether MEK inhibitors can boost current chemotherapy in KRAS-mutant lung tumors in clinic. Considering the genomic heterogeneity among patients with lung cancer, it is valuable
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NK Cells Mediate Synergistic Antitumor Effects of Combined Inhibition of HDAC6 and BET in a SCLC Preclinical Model.Cancer Research (IF 13.312) Pub Date : 2018-05-14 ,DOI:10.1158/0008-5472.can-18-0161Yan Liu,Yuyang Li,Shengwu Liu,Dennis O Adeegbe,Camilla L Christensen,Max M Quinn,Ruben Dries,Shiwei Han,Kevin Buczkowski,Xiaoen Wang,Ting Chen,Peng Gao,Hua Zhang,Fei Li,Peter S Hammerman,James E Bradner,Steven N Quayle,Kwok-Kin Wong
Small-cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic
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Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.Nature Medicine (IF 87.241) Pub Date : 2018-May-0 ,DOI:10.1038/s41591-018-0007-9Jacqulyne P. Robichaux,Yasir Y. Elamin,Zhi Tan,Brett W. Carter,Shuxing Zhang,Shengwu Liu,Shuai Li,Ting Chen,Alissa Poteete,Adriana Estrada-Bernal,Anh T. Le,Anna Truini,Monique B. Nilsson,Huiying Sun,Emily Roarty,Sarah B. Goldberg,Julie R. Brahmer,Mehmet Altan,Charles Lu,Vassiliki Papadimitrakopoulou,Katerina Politi,Robert C. Doebele,Kwok-Kin Wong,John V. Heymach
Although most activating mutations of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancers (NSCLCs) are sensitive to available EGFR tyrosine kinase inhibitors (TKIs), a subset with alterations in exon 20 of EGFR and HER2 are intrinsically resistant and lack an effective therapy. We used in silico, in vitro, and in vivo testing to model structural alterations induced by exon 20
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Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with Osimertinib.Clinical Cancer Research (IF 13.801) Pub Date : 2018-01-03 ,DOI:10.1158/1078-0432.ccr-17-1875Shengwu Liu,Shuai Li,Josephine Hai,Xiaoen Wang,Ting Chen,Max M Quinn,Peng Gao,Yanxi Zhang,Hongbin Ji,Darren A E Cross,Kwok-Kin Wong
Purpose:HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2% to 6% of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKI). However, due to limited preclinical studies and clinical trials, currently there is still no available standard
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Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers.Clinical Cancer Research (IF 13.801) Pub Date : 2017-08-20 ,DOI:10.1158/1078-0432.ccr-17-1098Josephine Hai,Shengwu Liu,Lauren Bufe,Khanh Do,Ting Chen,Xiaoen Wang,Christine Ng,Shuai Li,Ming-Sound Tsao,Geoffrey I Shapiro,Kwok-Kin Wong
Purpose:KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multitargeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential
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Prostate cancer–associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4Nature Medicine (IF 87.241) Pub Date : 2017-08-14 ,DOI:10.1038/nm.4378Xiangpeng Dai,Wenjian Gan,Xiaoning Li,Shangqian Wang,Wei Zhang,Ling Huang,Shengwu Liu,Qing Zhong,Jianping Guo,Jinfang Zhang,Ting Chen,Kouhei Shimizu,Francisco Beca,Mirjam Blattner,Divya Vasudevan,Dennis L Buckley,Jun Qi,Lorenz Buser,Pengda Liu,Hiroyuki Inuzuka,Andrew H Beck,Liewei Wang,Peter J Wild,Levi A Garraway,Mark A Rubin,Christopher E Barbieri,Kwok-Kin Wong,Senthil K Muthuswamy,Jiaoti Huang,Yu
Recurrent mutations in SPOP-encoding a Cullin 3-based E3 ubiquitin ligase- in prostate cancer disrupt the recognition and degradation of ubiquitination substrates, including BET proteins. Consequently, stability of BET proteins is enhanced and this increases the resistance to BET inhibitors in SPOP-mutant prostate tumors. These results, together with those in Janouskova et al. and Zhang et al., uncover
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Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4.Nature Medicine (IF 87.241) Pub Date : 2017-Sep-0 ,DOI:10.1038/nm.4378Xiangpeng Dai,Wenjian Gan,Xiaoning Li,Shangqian Wang,Wei Zhang,Ling Huang,Shengwu Liu,Qing Zhong,Jianping Guo,Jinfang Zhang,Ting Chen,Kouhei Shimizu,Francisco Beca,Mirjam Blattner,Divya Vasudevan,Dennis L Buckley,Jun Qi,Lorenz Buser,Pengda Liu,Hiroyuki Inuzuka,Andrew H Beck,Liewei Wang,Peter J Wild,Levi A Garraway,Mark A Rubin,Christopher E Barbieri,Kwok-Kin Wong,Senthil K Muthuswamy,Jiaoti Huang,Yu
The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins enhance the oncogenic functions of major cancer drivers by elevating the expression
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Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non–Small Cell Lung CancerCancer Discovery (IF 38.272) Pub Date : 2017-08-01 ,DOI:10.1158/2159-8290.cd-16-1020Dennis O. Adeegbe, Yan Liu, Patrick H. Lizotte, Yusuke Kamihara, Amir R. Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L. Guerriero, Shiwei Han, Mark M. Awad, David A. Barbie, Jerome Ritz, Simon S. Jones, Peter S. Hammerman, James Bradner, Steven N. Quayle, Kwok-Kin
Effective therapies for non–small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein, we evaluated the immunoregulatory properties of histone deacetylase (HDAC)
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Enhanced expression and phosphorylation of Sirt7 activates smad2 and ERK signaling and promotes the cardiac fibrosis differentiation upon angiotensin-II stimulation.PLOS ONE (IF 3.752) Pub Date : 2017-06-06 ,DOI:10.1371/journal.pone.0178530Haichen Wang,Shengwu Liu,Shengqiang Liu,Wei Wei,Xiaolong Zhou,Fang Lin,Juanjuan Wang,Jinye Chen,Guodong Zhang,Yongbing Pang
Cardiac fibroblasts (CFs) phenotypic conversion to myofibroblasts (MFs) represents a crucial event in cardiac fibrosis that leads to impaired cardiac function. However, regulation of this phenotypic transformation remains unclear. Here, we showed that sirtuin-7 (Sirt7) plays an important role in the regulation of MFs differentiation. Sirt7 expression and phosphorylation were upregulated in CFs upon
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CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer.Theranostics (IF 11.6) Pub Date : 2017-01-04 ,DOI:10.7150/thno.16752Chong Li,Shengwu Liu,Ruping Yan,Ning Han,Kwok-Kin Wong,Lei Li
Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in
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Micro-fractional Epidermal Powder Delivery for Skin Vaccination.Methods in Molecular Biology Pub Date : 2016-04-15 ,DOI:10.1007/978-1-4939-3389-1_46Feng Jia,Shengwu Liu,Mei X Wu,Xinyuan ChenSkin is a highly immunogenic site for vaccine delivery due to its richness of antigen-presenting cells. Several vaccines have been approved for skin delivery and in particular intradermal delivery in the last two decades. Yet intradermal delivery often causes frequent and severe local reactions, preventing the incorporation of adjuvants to further boost skin vaccination. Here we describe a novel skin ...
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PS341 inhibits hepatocellular and colorectal cancer cells through the FOXO3/CTNNB1 signaling pathway.Scientific Reports (IF 4.996) Pub Date : 2016-Feb-2 ,DOI:10.1038/srep22090Zhao Yang,Shengwu Liu,Mingao Zhu,Hong Zhang,Ji Wang,Qian Xu,Kaisu Lin,Xiumin Zhou,Min Tao,Chong Li,Hong Zhu
Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Particularly, a large number of patients with CRC also have liver metastasis. Currently, there are just a few targeted drugs against these two kinds of tumors which can only benefit a very small population of patients. Therefore, the need of more effective therapeutic drugs or strategies for
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Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells.PLOS ONE (IF 3.752) Pub Date : 2014-08-06 ,DOI:10.1371/journal.pone.0104426Kai Fu,Qin Cheng,Zhenwei Liu,Zhen Chen,Yan Wang,Honggang Ruan,Lu Zhou,Jie Xiong,Ruijing Xiao,Shengwu Liu,Qiuping Zhang,Daichang Yang
Human serum albumin (HSA) is extensively used in clinics to treat a variety of diseases, such as hypoproteinemia, hemorrhagic shock, serious burn injuries, cirrhotic ascites and fetal erythroblastosis. To address supply shortages and high safety risks from limited human donors, we recently developed recombinant technology to produce HSA from rice endosperm. To assess the risk potential of HSA derived
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T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-gamma production of natural killer cells via beta-arrestin 2-mediated negative signaling.Journal of Biological Chemistry (IF 5.486) Pub Date : 2014 Jun 2 ,DOI:10.1074/jbc.m114.572420Man Li,Pengyan Xia,Ying Du,Shengwu Liu,Guanling Huang,Jun Chen,Honglian Zhang,Ning Hou,Xuan Cheng,Luyu Zhou,Peifeng Li,Xiao Yang,Zusen Fan
Natural killer (NK) cell activation is well orchestrated by a wide array of NK cell receptor repertoire. T-cell immunoglobulin and ITIM domain (TIGIT) receptor was recently defined as an inhibitory receptor that is expressed on NK cells and T cells. TIGIT receptor/poliovirus receptor (PVR) ligand engagement signaling inhibits cytotoxicity mediated by NK and CD8(+) T cells. However, it is unclear how
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Activated ERM protein plays a critical role in drug resistance of MOLT4 cells induced by CCL25.PLOS ONE (IF 3.752) Pub Date : 2013-01-09 ,DOI:10.1371/journal.pone.0052384Li Zhang,Ruijing Xiao,Jie Xiong,Jun Leng,Altaf Ehtisham,Yi Hu,Qianshan Ding,Hui Xu,Shengwu Liu,Jin Wang,Dean G Tang,Qiuping Zhang
We have previously demonstrated that the CCR9/CCL25 signaling pathway plays an important role in drug resistance in human acute T-lymphocytic leukemia (T-ALL) by inducing activation of ERM protein with polarized distribution in T-ALL cell line MOLT4. However, the mechanism of action of the activated ERM protein in the drug resistance of MOLT4 cells induced by CCL25 remains uncharacterized. Here we
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Identification of SERPINB1 as a physiological inhibitor of human granzyme H.The Journal of Immunology (IF 5.426) Pub Date : 2012-12-28 ,DOI:10.4049/jimmunol.1202542Li Wang,Qian Li,Lianfeng Wu,Shengwu Liu,Yong Zhang,Xuan Yang,Pingping Zhu,Honglian Zhang,Kai Zhang,Jizhong Lou,Pingsheng Liu,Liang Tong,Fei Sun,Zusen Fan
The granzyme/perforin pathway is a major mechanism for cytotoxic lymphocytes to eliminate virus-infected and tumor cells. The balance between activation and inhibition of the proteolytic cascade must be tightly controlled to avoid self damage. Granzyme H (GzmH) is constitutively expressed in NK cells and induces target cell death; however, how GzmH activity is regulated remains elusive. We reported
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Identification of SERPINB1 As a Physiological Inhibitor of Human Granzyme HThe Journal of Immunology (IF 5.426) Pub Date : 2012-12-26 ,DOI:10.4049/jimmunol.1202542Li Wang, Qian Li, Lianfeng Wu, Shengwu Liu, Yong Zhang, Xuan Yang, Pingping Zhu, Honglian Zhang, Kai Zhang, Jizhong Lou, Pingsheng Liu, Liang Tong, Fei Sun, Zusen Fan
The granzyme/perforin pathway is a major mechanism for cytotoxic lymphocytes to eliminate virus-infected and tumor cells. The balance between activation and inhibition of the proteolytic cascade must be tightly controlled to avoid self damage. Granzyme H (GzmH) is constitutively expressed in NK cells and induces target cell death; however, how GzmH activity is regulated remains elusive. We reported
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Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif.The Journal of Immunology (IF 5.426) Pub Date : 2011-12-14 ,DOI:10.4049/jimmunol.1101381Li Wang,Kai Zhang,Lianfeng Wu,Shengwu Liu,Honglian Zhang,Qiangjun Zhou,Liang Tong,Fei Sun,Zusen Fan
Human granzyme H (GzmH) is constitutively expressed in human NK cells that have important roles in innate immune responses against tumors and viruses. GzmH is a chymotrypsin-like serine protease. Its substrate preference and its mechanism of substrate recognition are poorly understood. To provide structural insights into the substrate recognition mechanisms for GzmH, we solved the crystal structures
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