Bronx Comprehensive Sickle Cell Center

该建议包括：一个临床项目L_Proje-t 2：PI：Fabry博士)，该项目建立在PI在以下领域的开创性工作的基础上： LA Cycle关于BOLD-MRI的发展，现在用近红外光谱(NIRS)来测量氧合：。 养老金和血量吧，镰刀细胞患者和新型镰刀转基因小鼠。我们的目标是确定这些 最先进的技术可以帮助评估sicMe对大脑、肾脏和肌肉的损害。此外，还有 是三个翻译！研究项目，旨在寻找对SCD潜在有用的治疗干预措施 临床前发展的几个基本研究策略。他们是：项目I(Pi：Dr.Acharya)谁感兴趣 产生比聚合HbF更具聚合抑制潜力的珠蛋白链，基于 在上一个周期中，开创性的研究表明，猪-Sigma链完全神经化了人类B5-聚合体。 为了定义足以赋予人类所需特性的猪-伽马链序列的最小数目 伽马珠蛋白链。在这个过程中，我们将了解镰刀形聚合物的五元结构以及 半合成。项目3(PI：Kaul博士)也建立在上一个周期所做工作的基础上，但本提案的目的是 在知识的巨大飞跃中：测试以下假设：红细胞整合素的异质阵列和 VWF、P-选择素、层粘连蛋白和NO参与镰状粘连，并验证了伽马、β3、阴离子 多糖和羟基脲在阻止镰状细胞黏附方面很有用。项目4(PI；Nagel博士)，建立在 长期以来，人们对钛、乳铁蛋白基因参与镰刀表型的研究很感兴趣。这个项目旨在通过最先进的技术来定义 微阵列技术，镰状细胞性贫血的多效性基因，以及这些基因中的哪些 有上位性(修饰者)能力来定义严重风险并探索B基因簇中潜在的表观遗传效应 与镰刀基因连锁的单倍型。这些项目由行政核心、跨性别核心(在 开发镰刀动物模型的前沿)，由微芯片核心(也应该是我们内部的微阵列 设施)，这是一个强大的临床和患者服务核心，率先将日间医院的概念变为现实， 治疗伴有简单痛苦危象的镰状细胞性贫血患者的目的是以一种大大提高其发生率的方式 在康复方面，他们的住院率也有利地影响住院时间。这项建议 由上述两项补充--由两项高于上限的临床项目提案补充，这两项提案都是基于上一个周期的成就。

This proposal includes: one clinical Project l_Proje-t 2: PI: Dr. Fabry) that builds on the pioneering work of the Pi in the .: la cycle on the development of BOLD-MRI and now near infrared spectroscopy (NIRS) to measure oxygenation:. pension and blood volume it, sickle cell patients and novel sickle transgenic mice. The objective is to determine if these state-of-the-art technologies can help in the evaluation ofsicMe damage to brain, kidney and muscle. In addition, there are three Translationa! Research projects, that aim at finding potentially helpful therapeutic interventions in SCD by the pre-clinical development of several basic research strategies. They are: Project I (PI: Dr. Acharya) who is interested in generating a globin chain that has more polymerization inhibitory potential than the paradigmane HbF, based on the pioneering f'mding, in the previous cycle, that pig-sigma-chain completely neurralizes human B5-polymerization.The follow-up to define the minimum number of pig-gamma-chain sequences that are sufficient to confer the desired properties on the human Gamma globin chain. In the process, we will learn about the quinary structure of sickle polymer as well as the refinement of semisynthesis. Project 3 (PI: Dr. Kaul), also builds on work done in the previous cycle, but the present proposal aims at a quantum leap of knowledge as it pertains to: testing the hypotheses that a heterogenous array of red cell integrins and vWF, P-selectin, laminin, and NO are involved in sickle adhesion, and testing the hypothesis that gamma, beta3, anionic polysacharides, and hydroxyur, can be useful in blocking sickle cell adhesion. Project 4 (PI; Dr. Nagel), builds on a long interest in ti,.emulfigene involvement in the sickle phenotype. This project aims at defining, by state-of-the art microarray technology, the genes responsible for the pleiotropic effects in sickle cell anemia, as well as which of these have epistatic (modifier) capability to define severity risk and to explore potential epigenetic effects in B-gene cluster haplotypes linked to the sickle gene. The projects are supported by an Administrative Core, Transgecnic Core (in the forefront of developing sickle animal models), by a micro-CHIP Core (supposed also by our in-house Microarray Facility), a strong Clinical and Patient Services Core, that have pioneered the Day Hospital concept into reality, with the purpose of treating sickle cell anemia patients with uncomplicated painful crises in a way that greatly improves their rate of recovery, their hospitalization rates that also favorably affects the in house hospitalization length of stay. This proposal is complemented by two above-the caplemented by two above -the-cap Clinical Project Proposals, both based on last cycle accomplishments.