Dendritic cells in psoriasis and effects of efalizumab

候选人：我是一名皮肤科医生（医学博士），我的职业目标是成为一名独立的医生- 人类皮肤转化研究的科学家，特别是在牛皮癣领域。我提议成为 一个多学科的以病人为导向的研究人员，与一些技术，其中 将允许我适当地和深入地研究治疗、机制和病理学问题。 环境：洛克菲勒大学是一所世界知名的机构，拥有丰富的板凳历史。 research.它提供了一个理想的环境，开展这种类型的临床研究与专门的GCRC- 研究型医院，优秀的实验室，优秀的核心设施和设备，创新的 为转化研究学员提供的临床学者计划，以及一些鼓舞人心的讲座和研讨会 程序.洛克菲勒大学没有收费的医疗服务，所以我可以100%的投入我的时间。 这个职业发展计划。 研究项目：Psleep提供了一个很好的1型自身免疫模型， 理想的银屑病研究动物模型。在依法利珠单抗（抗-CD 11 a）用于 在银屑病中，我们鉴定了一种新型的皮肤树突状细胞（DC）（CD 11 c+，HLA-DR+，CD 86+，CD 40+）， 其构成银屑病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小鼠TNF-α和一氧化氮的人类等价物。 合成酶（iNOS）-产生（TIP）-DC。我计划开始复杂DC子集的基本表征， 存在于人类的血液和皮肤中，使用依法利珠单抗作为调节银屑病疾病活性的工具， 不同DC亚群对疾病发病机制的贡献可以更好地细化。此外，我将 确定依法利珠单抗对DC的生长、分化和活化具有直接影响的程度 与通过T细胞调节的间接效应相比。

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.