ABO ANTIBODIES--PARADIGM FOR HUMAN REPERTOIRE EVOLUTION

描述 （摘自申请人摘要）本申请为期五年， 计划候选人发展必要的技能和经验， 联合收割机基础科学研究与输液教学实践相结合 药 候选人已经完成了三年的正式居住 培训，是临床病理学委员会认证，并一直在 他的共同赞助者的实验室获得初步数据， 问题研究 候选人的基本研究兴趣在于抗原性和 体液免疫反应的发展，特别是抗体 多样性和特异性的发展。 对人类ABO血型系统的免疫应答是普遍存在的， 输血医学和同种异体输血中最重要的决定因素 移植 尽管它是在近世纪前被发现的， 目前还不知道抗ABO抗体的结构和多样性， 分子水平。 这在很大程度上是由于生产的困难 人源抗ABO单克隆抗体的体外研究 拟议的研究将 利用最近描述的噬菌体展示系统分离-和 表达重组人抗ABO抗体。 抗体分子 由此产生的将被用来询问与结构有关的基本问题 和优良的特异性的ABO抗体产生的个人的血液 A、B和0组。 这些信息将有助于了解 在分子水平上的抗ABO抗体库， 导致在临床中免疫调节这种反应的新方法， 输血、新生儿溶血病和固体 器官骨髓和异种移植 赞助者的实验室，唐·西格尔博士和史蒂文·斯皮塔尼克博士， 提供一个独特和理想的环境，在其中进行拟议的 研究项目。 西格尔博士在介绍 噬菌体展示技术进入输血医学领域。 博士斯皮塔尼克是一位公认的研究红色特征的专家 细胞糖抗原/抗体相互作用。 张博士的 赞助者是莱斯博士领导的输血医学部门的一部分 西尔伯斯坦是候选人提议的咨询委员会的成员， 最近建立了一个由NHLBI资助的专业研究中心， 输血医学和生物学。 沿着候选人的提议 分子建模和表面等离子体领域的顾问 共振，张博士将获得技术和专业知识， 作为一个独立的免疫血液学领域的未来贡献 临床科学家 (End摘要）

DESCRIPTION (Adapted from applicants' abstract) This application comprises a five-year plan for the candidate to develop the skills and experience necessary to combine basic science research with the teaching and practice of Transfusion Medicine. The candidate has completed three years of formal residency training, is board certified in Clinical Pathology, and has been working in his co-sponsors' laboratories acquiring preliminary data for the proposed studies. The candidate's basic research interests lie in antigenicity and the development of humoral immune responses, particularly in antibody diversity and the development of specificity. The immune response to the human ABO blood group system is ubiquitous and is the most important determinant in Transfusion Medicine and allogeneic transplantation. Despite its discovery nearly a century ago, essentially nothing is known about the structure and diversity of anti-ABO antibodies on a molecular level. This is in large part due to the difficulty in producing human monoclonal anti-ABO antibodies in vitro. The proposed research will utilize a recently-described bacteriophage display system for isolating- and expressing recombinant human anti-ABO antibodies. The antibody molecules thus produced will be used to ask basic questions relating to the structure and fine specificity of ABO antibodies produced by individuals of blood groups A, B, and 0. This information will provide an understanding of the repertoires of anti-ABO antibodies at a molecular level which may eventually lead to novel methods for immunomodulating this response in the clinical settings of blood transfusion, hemolytic disease of the newborn, and solid organ, bone marrow, and xeno-transplantation. The laboratories of the sponsors, Drs. Don Siegel and Steven Spitalnik, provide a unique and ideal environment in which to undertake the proposed research project. Dr. Siegel has been instrumental in introducing bacteriophage display technology into the field of Transfusion Medicine. Dr. Spitalnik is a well-recognized expert in the characterization of red cell carbohydrate antigen/antibody interactions. Together, Dr. Chang's sponsors are part of a Transfusion Medicine section led by Dr. Les Silberstein, a member of the candidate's proposed advisory committee, which has recently established an NHLBI-funded Specialized Center of Research in transfusion Medicine and Biology. Along with the candidate's proposed consultants in the areas of molecular modeling and surface plasmon resonance, Dr. Chang will gain the technical and professional expertise to make future contributions to the field of immunohematology as an independent clinical scientist. (End of Abstract)