NIAMS: CORT (Psoriasis Center of Research Translation)

描述(申请人提供)：设在大学医院病例医学中心的牛皮癣研究翻译中心将整合强大的牛皮癣和皮肤病研究基地与现有的大量牛皮癣患者。来自新的大学医院Murdough家庭牛皮癣中心的500万美元将进一步增强临床转介网络的能力和地理位置，与凯斯医学院为牛皮癣招聘提供的200万美元相结合，这些资源构成了对CORT的重大机构承诺。皮肤病研究中心的皮肤生物学基础设施和经验将加速牛皮癣患者皮肤科的进步，造福牛皮癣患者。设想的翻译项目将测试基于新的机制发现的牛皮癣的创新治疗干预措施。他们还利用患者和动物模型的生物样本提供了新的致病信息。每个项目的目的是产生改变牛皮癣患者治疗方式的治疗方式。项目1是一项新的光动力疗法(PDT)I期机制、安全性和初步疗效研究，该项目还开发了一种实时患者优化治疗设备。项目2是一项基础研究，旨在确定S100蛋白在牛皮癣发病机制中的新作用，包括通过异种移植对S100和巨噬细胞在牛皮癣皮肤中的相互作用进行原理验证测试。项目3利用一种新的牛皮癣样皮炎转基因小鼠模型来研究血管内皮生长因子、S100 A8/9和血管变化在加剧银屑病中的潜在作用。项目4探讨了牛皮癣患者心血管风险较高的新临床发现是否与S100 A8/9过度表达有关，并探讨了针对S100血清水平的激进牛皮癣治疗是否改善了心血管风险。这些研究将得到A)统计学和B)系统生物学两个以项目为重点的科学核心和一个行政核心的支持。一个由男性和女性患者以及父母(其中一些人也是著名科学家)组成的咨询委员会将监督CORT和P&F审查。因此，CORT将把一个由来自不同部门和学科的翻译内科科学家、护士、社区临床医生、普通人和基础科学家组成的多学科团队聚集在一起，将该机构的智力和科学资源应用于牛皮癣患者的新疗法。

DESCRIPTION (provided by applicant): A Center of Research Translation in Psoriasis based at University Hospitals Case Medical Center will integrate a strong psoriasis and skin disease research base with a large existing cohort of psoriasis patients. $5M from the new University Hospitals Murdough Family Center for Psoriasis will further increase the capabilities and geography of the clinical referral network, and in combination with $2M from Case School of Medicine for recruitment in psoriasis, these resources comprise a substantial institutional commitment to the CORT. The Skin Diseases Research Center's cutaneous biology infrastructure and experience will accelerate the Case Psoriasis CORT's advances for psoriasis patient benefit. The translational projects envisioned will test innovative therapeutic interventions in psoriasis that are based upon new mechanistic findings. They also provide new pathogenetic information using biologic samples from patients and animal models. It is intended that each Project will generate therapeutic modalities that change the treatment of psoriasis patients. Project 1 is a novel photodynamic therapy (PDT) Phase I mechanistic, safety, and preliminary efficacy study which also develops a real-time patient-optimized therapy device. Project 2 is a basic study that determines novel roles for S100 proteins in the pathogenesis of psoriasis, including proof-of-principle testing of S100 and macrophage interplay in psoriasis skin on xenogenic transplants. Project 3 takes advantage of a novel transgenic mouse model of psoriasiform dermatitis to examine the potential role of VEGF, S100 A8/9 and vascular changes exacerbating psoriasis. Project 4 explores whether the new clinical finding that psoriasis patients are at higher cardiovascular risk is related to S100 A8/9 overexpression and addresses if aggressive psoriasis treatment directed at S100 serum levels improves cardiovascular risk. The studies will be supported by two project-focused scientific Cores in A) Statistics and B) Systems Biology, and by an Administrative Core. An Advisory Board with representation by both male and female patients, as well as parents, some of whom are also renowned scientists, will oversee the CORT and the P&F review. The CORT will thus bring a multidisciplinary team of translational physician scientists, nurses, community clinicians, laity, and basic scientists from different departments and disciplines together to apply the intellectual and scientific resources of the institution to new therapies for psoriasis patients.