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Generation and repair of AID-initiated DNA lesions in B lymphocytes

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Frontiers of Medicine 2014年第2期8卷 201-216页

作者： Zhangguo Chen Jing H. Wang Integrated Department of Immunology University of Colorado Anschutz Medical Campus and National Jewish Health Denver CO 80206USA

Activation-induced deaminase （AID） initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation （SHM） and class switch recombination （CSR）, both of which require AID. AID induces U：G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunogiobulin （Ig） loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词： class switch recombination somatic hypermutation activation-induced deaminase DNA repair genomic instability

Mechanisms and impacts of chromosomal translocations in cancers

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Frontiers of Medicine 2012年第3期6卷 263-274页

作者： Jing H.Wang Integrated Department of Immunology University of Colorado School of Medicine and National Jewish HealthDenverCO 80206USA

Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years *** translocations,a type of particular structural changes involving heterologous chromosomes,have made a critical impact on diagnosis,prognosis and treatment of *** example,the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous *** the past few decades,tremendous progress has been achieved towards elucidating the mechanism causing chromosomal *** review focuses on the basic mechanisms underlying the generation of chromosomal *** particular,the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.

关键词： DNA double strand breaks chromosomal translocations genomic instability spatial proximity carcinogenesis

Recognition of self and altered self by T cells in autoimmunity and allergy

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Protein & Cell 2013年第1期4卷 8-16页

作者： Lei Yin Shaodong Dai Gina Clayton Wei Gao Yang Wang John Kappler Philippa Marrack Howard Hughes Medical Institute and Integrated Department of Immunology National Jewish HealthDenverCO 80206USA Integrated Department of Immunology National Jewish HealthDenverCO80206USA Program in Structural Biology and Biophysics University of Colorado DenverSchool of MedicineAuroraCO 80045USA Department of Biochemistry and Molecular Genetics University of Colorado DenverSchool of MedicineAuroraCO 80045USA

T cell recognition of foreign peptide antigen and toler-ance to self peptides is key to the proper function of the immune ***,in the thymus T cells that rec-ognize self MHC+self peptides are deleted and those with the potential to recognize self MHC+foreign pep-tides are selected to *** there are excep-tions to these *** and allergy are two of the most common immune diseases that can be related to recognition of *** genes work together to lead to *** those,particular MHC alleles are the most strongly associated,reflecting the key importance of MHC presentation of self peptides in autoimmunity.T cells specific for combinations of self MHC and self pep-tides may escape thymus deletion,and thus be able to drive autoimmunity,for several reasons:the relevant self peptide may be presented at low abundance in the thy-mus but at high level in particular peripheral tissues;the relevant self peptide may bind to MHC in an unusual register,not present in the thymus but apparent else-where;finally the relevant self peptide may be post translationally modified in a tissue specific *** some types of allergy,the peptide+MHC combination may also be fully derived from *** the combi-nation in question may be modified by the presence of other ligands,such as small drug molecules or metal *** these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.

关键词： altered self neoantigen antigen presenting T cell recognition autoimmunity allergy diabetes der-matitis drug hypersensitivity

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Molecular mechanism of signaling by tumor necrosis factor

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Science China Life Sciences 2002年第2期45卷 113-119页

作者：查纪坤舒红兵 College of Life Sciences Peking University Beijing China national jewish Medical and Research Center Denver USA

Tumor necrosis factor (TNF) is an important cytokine with multiple biological effects, including cell growth, differentiation, apoptosis, immune regulation and induction of inflammation. The effects of TNF are mediated by two receptors, TNF-R1 and TNF-R2. The major signal trans-duction pathways triggered by TNF include those that lead to apoptosis, activation of transcription factor NF-κB and protein kinase JNK. This review will discuss the molecular mechanisms of these signaling pathways.

关键词： tumor necrosis factor signal transduction JNK kinase NF-κB apoptosis.

慢性阻塞性肺疾病全球倡议（GOLD）0期吸烟者胸部CT可视的肺气肿预测疾病进展：来自COPD基因流行病学研究组的结果

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国际医学放射学杂志 2020年第6期 735-736页

作者：王佳妮 A.S.Oh M.Strand K.Pratte E.A.Regan S.Humphries J.D.Crapo Department of Radiology National Jewish Health

摘要摘要根据目前的诊断标准,对于肺功能检查提示没有慢性阻塞性肺疾病(COPD)证据的病人,其CT影像上存在的可视性肺气肿的临床意义尚不清楚。目的通过与CT上无可

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Hands-on Workshops as An Efective Means of Learning Advanced Technologies Including Genomics,Proteomics and Bioinformatics

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Genomics, Proteomics & Bioinformatics 2013年第6期11卷 368-377页

作者： Nichole Reisdorph Robert Stearman Katerina Kechris Tzu Lip Phang Richard Reisdorph Jessica Prenni David J.Erle Christopher Coldren Kevin Schey Alexey Nesvizhskii Mark Geraci Department of Immunology National Jewish Health Department of Medicine Division of Pulmonary Sciences and Critical Care MedicineUniversity of Colorado School of Medicine Department of Biostatistics and Informatics Colorado School of Public Health Department of Pediatrics National Jewish Health Department of Biochemistry and Molecular Biology Proteomics and Metabolomics FacilityColorado State University Lung Biology Center Department of MedicineUniversity of California Bioinformatics PathgroupNashvilleTN 37027 USA Department of Biochemistry and Mass Spectrometry Research Center Vanderbilt School of Medicine Department of Pathology University of Michigan Medical School

Genomics and proteomics have emerged as key technologies in biomedical research, resulting in a surge of interest in training by investigators keen to incorporate these technologies into their research. At least two types of training can be envisioned in order to produce meaningful results, quality publications and successful grant applications：（1） immediate short-term training workshops and （2） long-term graduate education or visiting scientist programs. We aimed to fill the former need by providing a comprehensive hands-on training course in genomics, proteomics and informatics in a coherent, experimentally-based framework. This was accomplished through a national Heart, Lung, and Blood Institute （NHLBI）-sponsored 10-day Genomics and Proteomics Hands-on Workshop held at national jewish health （NJH） and the University of Colorado School of Medicine （UCD）. The course content included comprehensive lectures and laboratories in mass spectrometry and genomics technologies, extensive hands-on experience with instrumentation and software, video demonstrations, optional workshops, online sessions, invited keynote speakers, and local and national guest faculty. Here we describe the detailed curriculum and present the results of short- and long-term evaluations from course attendees. Our educational program consis- tently received positive reviews from participants and had a substantial impact on grant writing and review, manuscript submissions and publications.

关键词： Proteomics Mass spectrometry Genomics Bioinformatics Hands-on Workshops

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IL-27-mediated Th2 inhibition in asthma is impaired through SOCS3-STAT1 axis

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IL-27-mediated Th2 inhibition in asthma is impaired through ...

中华医学会呼吸病学年会——2013（第十四次全国呼吸病学学术会议）

作者： Zhihong Chen Shanze Wang Chunxue Bai Hua Huang Zhongshan Hospital Fudan University national jewish health

Rationale As a member of IL-6/IL-12 cytokine family, IL-27 has pleiotropic and complex biological function of both pro- and anti- *** has been shown to have the ability to inhibit inflammation and hyperresponsiveness in asthma mice model,but little is known about IL-27-midiated immune suppression in *** aim of the study is to explore the effect of IL-27 on Th2 differentiation in asthmatics and the downstream IL-27 signaling pathway. Methods Purify CD4+ T cells from human PBMC and mice spleen were cultured under Th2 or Th2 + IL-27

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来源： cnki会议评论

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哮喘：发病机制及新的治疗药物

英国医学杂志中文版 2015年第5期18卷 264-276页

作者： Tod Olin, assistant professor, director Michael E Wechsler, professor of medicine, director 赵志刚梁志欣 Pedlatric Exercise Tolerance Center Department Pediatrics of National Jewish Health Denver CO 80206 USA Asthma Program Department of Medicine National Jewish Health Denver CO USA 解放军总医院呼吸内科

在美国，近2000万人受到哮喘的影响，而在世界上，超过3亿多人受到哮喘的困扰。这些人中，10％-15％的患者是常用药物治疗无效的重症哮喘。由于现存的药物并不能改善所有哮喘患者的症状、控制急性期的发作，再加上可能产生副作用，因此... 详细信息

在美国，近2000万人受到哮喘的影响，而在世界上，超过3亿多人受到哮喘的困扰。这些人中，10％-15％的患者是常用药物治疗无效的重症哮喘。由于现存的药物并不能改善所有哮喘患者的症状、控制急性期的发作，再加上可能产生副作用，因此，需要新的治疗药物问世。在过去的10年中，对于哮喘的遗传学、气道生物学及免疫细胞的信号通路学研究取得了实质性的进展，这些进展推动了将来有可能改善哮喘症状的小分子药物和生物制剂的研发。一些新的哮喘药物，包括超长效的B受体激动剂和白细胞介素（IL）-4、IL-5、IL-13和IL-17通路的调节剂，在随机对照试验中已经得到了评价，而其他新的药物，包括游离糖皮质激素、CXC趋化因子受体2拮抗剂、Toll样受体9激动剂以及酪氨酸激酶抑制剂仍然在研发的早期阶段。尽管已获得了一些初步疗效数据，但还没有足够的证据来强烈推荐使用这些新药。为了减少世界范围内哮喘的发病率，今后，有必要对这些生物制剂的临床疗效、新药对儿童重症哮喘的作用、非嗜酸粒细胞增多以及糖皮质激素抵抗型哮喘的生物学等进行研究。

关键词：药物治疗发病机理哮喘

Emergency department utilization for gastrointestinal care and patient characteristics associated with hospital admission in a national cohort

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Gastroenterology Report 2023年第1期11卷 566-568页

作者： Kelly Suchman Nina Kohn Arvind J.Trindade Division of Gastroenterology Zucker School of Medicine at Hofstra/NorthwellLong Island Jewish Medical CenterNew Hyde ParkNYUSA Institute of health Innovations and Outcomes Research Feinstein Institutes for Medical ResearchNorthwell HealthManhassetNYUSA

Introduction Gastrointestinal diseases and care in the USA account for a significant amount of healthcare resources and spending,recently totaling>$119 billion dollars annually[1].In addition to ambulatory sites and clinics,a substantial portion of gastrointestinal care occurs through the emergency department(ED).Though the overall rate of ED visits in the USA has remained stable over the past 10 years[2],the number of visits for gastrointestinal complaints has been increasing[1,3],contributing to rising healthcare costs.

关键词： gastrointestinal diseases ambulatory