Dendritic cells in psoriasis and effects of efalizumab

描述（由申请人提供）：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的医生科学家在人类翻译皮肤研究，特别是在银屑病领域。我建议成为一个多学科的患者为导向的研究人员，与一些技术，这将使我能够适当和深入地调查治疗，机制和病理问题的优秀把握。环境：洛克菲勒大学是一所世界知名的机构，拥有丰富的临床研究历史。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资助的研究医院，优秀的实验室，优秀的核心设施和设备，创新的临床学者计划的转化研究学员，以及几个鼓舞人心的讲座和研讨会计划。洛克菲勒大学没有收费服务的医学，所以我可以把100%的时间投入到这个职业发展计划中。 研究项目：银屑病提供了一种很好的1型自身免疫模型，目前还没有理想的银屑病动物模型可供研究。在依法利珠单抗（抗CD 11 a）治疗银屑病的临床试验中，我们鉴定了一种新型皮肤树突状细胞（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产生TNF和诱导型一氧化氮合酶（iNOS）的（TIP）-DC的人等效物。我计划开始对人类血液和皮肤中存在的复杂DC亚群进行基本表征，使用依法利珠单抗作为调节银屑病疾病活动的工具，以便更好地细化不同DC亚群对疾病发病机制的贡献。此外，我将确定依法利珠单抗对DC的生长、分化和活化的直接影响与通过T细胞调节的间接影响的程度。

DESCRIPTION (provided by applicant): 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 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.