Multiple Sclerosis: Molecular Profile of Plasmacytoid Dendritic Cells

多发性硬化症：浆细胞样树突状细胞的分子概况

基本信息

批准号：
7608717
负责人：
KONSTANTIN E. BALASHOV
金额：
$ 17.86万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7608717
关键词：
Agonist Antigen-Presenting Cells Antiviral Agents Biometry Blood Cells Cells Central Nervous System Diseases Clinical Clinical Investigator Data Demyelinating Diseases Dendritic Cells Dentistry Disease Disease remission Doctor of Medicine Doctor of Philosophy Elements Functional disorder Funding Gene Expression Generations Genes Genomics Goals Human Immune Immunology In Vitro Individual Interferon Type II Interferon-alpha Interferon-beta Interferons Knowledge Learning Ligands Link Mediating Medicine Mentorship Methods Molecular Molecular Biology Molecular Profiling Multiple Sclerosis Neurology New Jersey Patients Pattern Population Production Proteins Proteomics Reporting Research Personnel Research Project Grants Research Training Role Supervision T-Lymphocyte TLR9 gene Testing Th1 Cells Time Toll-Like Receptor Pathway Toll-like receptors Training Universities Viral Virus Diseases career chemokine cytokine experience in vivo novel pathogen patient oriented research prevent professor programs response skills viral RNA

项目摘要

DESCRIPTION (provided by applicant): The candidate, Konstantin Balashov, M.D., Ph.D., is an assistant professor of neurology at the University of Medicine and Dentistry of New Jersey. He is trained both in clinical neurology and human immunology. His immediate goal is to study the role of plasmacytoid dendritic cells (pDCs) and interferons in multiple sclerosis (MS) at a molecular level. His long-term career goal is to obtain the skills and experience necessary to develop into a funded independent clinical investigator with expertise in modern methods of immunology and genomics to study the pathophysiology of MS. The proposed five-year research training will provide skills for him in important aspects of patient-oriented research in MS. He will enhance his knowledge of biostatistics and genomics through formal coursework and supervision. He will learn the molecular biology and immunology of interferons under the guidance of Dr. Sidney Pestka. He will learn how to apply this knowledge to MS under the mentorship of Dr. Suhayl Dhib-Jalbut. The research project will capitalize o recent scientific progress in studies of pDCs, professional antigen-presenting cells, which secrete high amounts of chemokines which attract Th1 cells, and interferon-alpha which promotes generation of Th1 cells. pDCs can be activated by specific molecular patterns present in viral components through Toll-like receptors (TLRs). It is hypothesized that activation of pDCs by TLR agonists induces the generation of immunopathogenicThl cells and is associated with clinical exacerbation in MS patients. Interferon gamma, the Th1 type cytokine, and viral infections were shown to be linked to clinical exacerbation in MS. Thus, pDCs may be the key element connecting viral infection and clinical exacerbation in MS patients. Dr. Balashov will apply modern methods of genomics and proteomics to identify expression of thousands of genes and production of multiple cytokines in small cell population of pDCs isolated from MS patients. This will help to link activation of pDCs and clinical exacerbation in MS patients. Relevance: If the above hypothesis is true, small molecular substances called TLR antagonists could be tested as a new promising treatment for multiple sclerosis. TLR antagonists would prevent activation of plasmacytoid dendritic cells by viral pathogens and, therefore, the clinical exacerbation of the disease.

描述（由申请人提供）：候选人Konstantin Balashov，医学博士，博士，是新泽西大学医学和牙科的神经病学助理教授。他接受了临床神经病学和人类免疫学的培训。他的近期目标是研究分子水平多发性硬化症（MS）中质细胞类动物树突状细胞（PDC）和干扰素的作用。他的长期职业目标是获得具有现代免疫学和基因组学方法专业知识的资助的独立临床研究者所必需的技能和经验，以研究MS的病理生理学。拟议的五年研究培训将在MS中注重患者研究的重要方面为他提供技能。他将通过正式的课程和监督来增强他对生物统计学和基因组学的了解。在西德尼·佩斯卡（Sidney Pestka）博士的指导下，他将学习干扰素的分子生物学和免疫学。在Suhayl Dhib-Jalbut博士的指导下，他将学习如何将这些知识应用于MS。该研究项目将利用o在PDC的研究，专业抗原呈递细胞的最新科学进步，这些细胞分泌大量吸引Th1细胞的趋化因子以及促进Th1细胞产生的干扰素α。 PDC可以通过Toll样受体（TLR）中存在于病毒成分中的特定分子模式来激活PDC。假设TLR激动剂对PDC的激活诱导了免疫致病细胞的产生，并且与MS患者的临床加剧有关。干扰素伽马，Th1型细胞因子和病毒感染与MS中的临床加重有关。因此，PDC可能是连接病毒感染和MS患者临床加重的关键元素。 Balashov博士将采用现代基因组学和蛋白质组学方法来鉴定数千种基因的表达，并在从MS患者中分离出的PDC的小细胞群中多种细胞因子的产生。这将有助于将PDC的激活与MS患者的临床加重联系起来。相关性：如果上述假设是正确的，则可以将称为TLR拮抗剂的小分子物质作为多发性硬化症的新有前途的治疗方法进行测试。 TLR拮抗剂将防止病毒病原体激活浆细胞样树突状细胞，因此会激活该疾病的临床加重。