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NF kappa B Activity in Skin Inflammation and Carcinogenesis

NF kappa B 在皮肤炎症和癌变中的活性

基本信息

批准号：
8514524
负责人：
Brian Poligone
金额：
$ 12.09万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-25 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514524
关键词：
Apoptosis Binding Biology Birth Cell Nucleus Cell Surface Receptors Cells Chronic Complex Consensus Cutaneous Cytoplasm Development Disease Doctor of Philosophy Dysplasia Epithelial Family member Gene Expression Genes Genetically Engineered Mouse Goals Heterozygote Hyperplasia Incidence Inflammation Inflammation Mediators Inflammatory Instruction Knock-in Mouse Lead Life Ligands Link Lymphoid Cell Malignant Neoplasms Molecular Mus Mutation NF-kappa B Neoplasm Metastasis Oncogenic Pathway interactions Patient Care Phenotype Phosphotransferases Play Predisposition Process Proteins Reporting Role Signal Transduction Site Skin Skin Cancer Skin Neoplasms Skin Papilloma Switch Genes Tissues Transcriptional Activation Tumor Necrosis Factor Receptor Tumor Necrosis Factor-alpha Ubiquitination Up-Regulation angiogenesis carcinogenesis career development improved interest keratinocyte mouse model multicatalytic endopeptidase complex mutant novel p65 promoter response skin disorder transcription factor tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): This application supports the career development of Brian Poligone, MD, PhD. who has an interest in the molecular signaling of NF-KB and its effect on the skin. The transcription factor NF-KB provides a regulatory on/off switch for gene expression that is important for inflammation and carcinogenesis. By understanding the role of NF-KB in the biology of keratinocytes and cutaneous lymphoid cells, inflammatory skin diseases and cancers may be better understood. We have constructed a novel mouse model to examine the NF-KB pathway in skin. The homozygous p65 S276D (PD) knock-in mouse contains a mutant form of NF-KB that increases the basal transcriptional activation of NF-KB dependent genes. Because studies on NF-KB activity in the skin have been underrepresented, detailed examination of the PD mouse should help clarify this central mediator of inflammation and tumorigenesis. Transcription factors are proteins that are the main on/off switch in regulating gene expression. NF-KB is a transcription factor that is known to be a central regulator of both inflammatory and oncogenic processes. Studying NF-KB in genetically engineered mouse models helps to clarify the role of NF-KB and allows a better understanding of its activity in inflammatory disease and cancer and ultimately may lead to improved patient care. RELEVANCE (See instructions): By understanding the basic mechanisms that lead to both skin inflammation and tumorigenesis, better treatments for skin disease are possible. It is through this basic understanding of skin disease that better treatments of can be identified.

描述（由申请人提供）：该申请支持Brian Poligone， MD， PhD的职业发展。她对NF-KB的分子信号传导及其对皮肤的影响感兴趣。转录因子NF-KB为基因表达提供了一个调控开关，这对炎症和癌变很重要。通过了解NF-KB在角质形成细胞和皮肤淋巴样细胞生物学中的作用，可以更好地了解炎症性皮肤病和癌症。我们建立了一种新的小鼠模型来检测皮肤中NF-KB通路。纯合子p65 S276D （PD）敲入小鼠含有NF-KB的突变形式，可增加NF-KB依赖基因的基础转录激活。由于对皮肤中NF-KB活性的研究一直缺乏代表性，因此对PD小鼠的详细检查应有助于阐明这种炎症和肿瘤发生的中心介质。转录因子是调节基因表达的主要开关蛋白。NF-KB是一种转录因子，已知是炎症和致癌过程的中心调节因子。在基因工程小鼠模型中研究NF-KB有助于阐明NF-KB的作用，并有助于更好地了解其在炎症性疾病和癌症中的活性，最终可能导致改善患者护理。相关性（见说明）：通过了解导致皮肤炎症和肿瘤发生的基本机制，可以更好地治疗皮肤病。正是通过对皮肤病的基本了解，才能确定更好的治疗方法。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Menus for managing patients with cutaneous T-cell lymphoma.

DOI：
10.1016/j.sder.2011.12.002
发表时间：
2012-03
期刊：
SEMINARS IN CUTANEOUS MEDICINE AND SURGERY
影响因子：
0
作者：
Poligone, Brian;Heald, Peter
通讯作者：
Heald, Peter

PKK suppresses tumor growth and is decreased in squamous cell carcinoma of the skin.

DOI：
10.1038/jid.2014.428
发表时间：
2015-03
期刊：
JOURNAL OF INVESTIGATIVE DERMATOLOGY
影响因子：
6.5
作者：
Poligone, Brian;Gilmore, Elaine S.;Alexander, Carolina V.;Oleksyn, David;Gillespie, Kathleen;Zhao, Jiyong;Ibrahim, Sherrif F.;Pentland, Alice P.;Brown, Marc D.;Chen, Luojing
通讯作者：
Chen, Luojing

The spectrum of pigmented purpuric dermatosis and mycosis fungoides: atypical T-cell dyscrasia.

色素性紫癜性皮肤病和蕈样肉芽肿病的谱系：非典型 T 细胞恶液质。