Dendritic cells in psoriasis and effects of efalizumab

牛皮癣中的树突状细胞和依法珠单抗的作用

基本信息

批准号：
7789527
负责人：
MICHELLE A LOWES
金额：
$ 13.54万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7789527
关键词：
Affect Animal Model Antibodies Antigens Apoptosis Area Autoimmune Diseases Autoimmunity Biological Response Modifier Therapy Biopsy Blood Blood Circulation Cell Communication Cell Maturation Cells Clinical Clinical Research Clinical Trials Color Complex Complex Mixtures Core Facility Cutaneous Dendritic Cells Dendritic cell activation Dermal Dermatologist Development Plans Differentiation and Growth Disease Doctor of Philosophy Endothelial Cells Environment Equipment Fee-for-Service Plans Funding Gene Expression Genes Genomics Genotype Goals HLA-DR Antigens Hospitals Human ITGAX gene In Vitro Infiltration Inflammation Inflammation Mediators Inflammatory Institution Laboratories Lesion Leukocytes Ligation Lymphocyte Function Medicine Methods Modeling Mus Myelogenous NCI Scholars Program Nitric Oxide Synthase Pathogenesis Pathologic Pathway interactions Patients Phenotype Physicians Population Psoriasis Punch Biopsy RNA Recording of previous events Research Research Personnel Research Project Grants Resolution Reverse Transcriptase Polymerase Chain Reaction Scientist Skin Surface Suspension substance Suspensions System T-Lymphocyte TNF gene TNFRSF5 gene Technology Therapeutic Time Translational Research Universities bench to bedside career career development cell type efalizumab grasp innovation keratinocyte lectures monocyte novel patient oriented peripheral blood programs research study skin disorder skin lesion tool volunteer

项目摘要

CANDIDATE: I am a dermatologist (MD PhD) and my broad career goal is to be an independent physician- scientist in human translational skin research, particularly in the area of psoriasis. I am proposing to become a multi-disciplinary patient-oriented researcher, with an excellent grasp of a number of technologies, which will allow me to investigate therapeutic, mechanistic and pathologic questions appropriately and deeply. ENVIRONMENT: Rockefeller University is a world-renowned institution with a rich history of bench-bedside research. It provides an ideal environment to carry out this type of clinical research with a dedicated GCRC- funded research hospital, outstanding laboratories, excellent core facilities and equipment, an innovative Clinical Scholars Program for translational research trainees, and several inspiring lecture and seminar programs. There is no fee-for-service medicine at Rockefeller University, so I can dedicate 100% of my time to this career development plan. RESEARCH PROJECT: Psoriasis offers an excellent model of type 1 autoimmunity, and there there is no ideal animal model of psoriasis to study. In the context of a clinical trial with efalizumab (anti-CD11a) for psoriasis, we identified a new type of cutaneous dendritic cell (DC) (CD11c+, HLA-DR+, CD86+, CD40+), which constitutes the most abundant type of leukocyte in psoriasis lesions. It also expresses TNF and iNOS, so these cells may be the human equivalent of recently described murine TNF- and indicible nitric oxide synthase (iNOS)-producing (TIP)-DCs. I plan to begin basic characterization of complex DC subsets that exist in blood and skin of humans, using efalizumab as a tool to modulate psoriasis disease activity, so that the contribution of different DC subsets to disease pathogenesis can be better refined. Furthermore, I will determine the extent to which efalizumab has direct effects on growth, differentiation and activation of DCs versus indirect effects through T cell modulation.

候选人：我是一名皮肤科医生（医学博士），我的广泛职业目标是成为一名独立医生 - 人类转化皮肤研究的科学家，特别是牛皮癣领域的科学家。我提议成为一位以患者为中心的多学科研究人员，精通多项技术，将使我能够适当而深入地研究治疗、机制和病理问题。环境：洛克菲勒大学是一所世界知名大学，拥有丰富的临床实践历史研究。它为开展此类临床研究提供了理想的环境，并配备了专门的 GCRC- 资助的研究型医院、优秀的实验室、优良的核心设施设备、创新的针对转化研究实习生的临床学者计划，以及一些鼓舞人心的讲座和研讨会程序。洛克菲勒大学不提供收费医疗，因此我可以投入 100% 的时间到这个职业发展计划。研究项目：银屑病提供了 1 型自身免疫的优秀模型，并且目前还没有研究银屑病的理想动物模型。在 efalizumab（抗 CD11a）的临床试验中银屑病，我们鉴定了一种新型皮肤树突状细胞 (DC)（CD11c+、HLA-DR+、CD86+、CD40+），它构成牛皮癣病变中最丰富的白细胞类型。它还表达 TNF 和 iNOS，因此，这些细胞可能是最近描述的鼠类 TNF- 和可指示一氧化氮的人类细胞产生合酶（iNOS）的（TIP）-DC。我计划开始对复杂的 DC 子集进行基本表征存在于人类的血液和皮肤中，使用efalizumab作为调节牛皮癣疾病活动的工具，以便可以更好地细化不同 DC 亚群对疾病发病机制的贡献。此外，我将确定 efalizumab 对 DC 生长、分化和激活的直接影响程度与通过 T 细胞调节产生的间接影响相比。