Dendritic cells in psoriasis and effects of efalizumab

候选人：我是一名皮肤科医生(医学博士)，我广泛的职业目标是成为一名独立的内科医生。 人类皮肤翻译研究的科学家，特别是牛皮癣领域的科学家。我打算成为一名 一位多学科的以患者为中心的研究人员，对多项技术有着出色的掌握，其中 将使我能够适当和深入地研究治疗性、机械性和病理学问题。 环境：洛克菲勒大学是一所世界知名的大学，有着丰富的病床护理历史 研究。它为开展这种类型的临床研究提供了理想的环境，并拥有专门的GCRC- 资助研究型医院，卓越的实验室，优秀的核心设施和设备，创新 临床学者计划转化型研究实习生，以及几个鼓舞人心的讲座和研讨会 程序。洛克菲勒大学没有按服务收费的药物，所以我可以100%地投入我的时间 这份职业发展计划。 研究项目：银屑病提供了一种优秀的1型自身免疫模型，没有 理想的银屑病动物模型进行研究。在一项使用efalizumab(抗CD11a)的临床试验中 在银屑病中，我们鉴定了一种新型的皮肤树突状细胞(DC)(CD11c+，HLA-DR+，CD86+，CD40+)， 构成了银屑病皮损中最丰富的白细胞类型。它还表达肿瘤坏死因子和诱导型一氧化氮合酶， 因此，这些细胞可能相当于人类最近描述的小鼠肿瘤坏死因子-和可标记的一氧化氮 产生合酶(INOS)的树突状细胞(TIP)。我计划开始描述复杂DC子集的基本特征 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，从而 不同DC亚群在疾病发病机制中的贡献可以得到更好的细化。此外，我会 确定efalizumab对DC的生长、分化和激活的直接影响程度 而不是通过T细胞调节的间接作用。

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.