ABO ANTIBODIES--PARADIGM FOR HUMAN REPERTOIRE EVOLUTION

描述 (摘自申请者摘要)本申请为期五年 为候选人制定计划，以发展必要的技能和经验 将基础科学研究与输液学教学实践相结合 医学。候选人已经完成了三年的正式居留 培训，获得临床病理学委员会认证，并一直在 他的联合赞助商的实验室正在为拟议的 学习。候选人的基础研究兴趣在于抗原性和 体液免疫反应的发展，特别是在抗体方面 多样性和发展的特殊性。 对人类ABO血型系统的免疫反应无处不在， 输血医学和同种异体移植中最重要的决定因素 移植。尽管它是在近一个世纪前发现的，但本质上 抗ABO抗体的结构和多样性目前尚不清楚。 一个分子水平。这在很大程度上是因为生产困难。 人源性抗ABO单抗的体外实验。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 这样产生的问题将被用来提出与结构有关的基本问题 血液中个体产生的ABO抗体具有良好的特异性 A、B和0组。这些信息将帮助您了解 在分子水平上的抗ABO抗体谱系，最终可能 导致在临床上免疫调节这种反应的新方法。 输血环境、新生儿溶血性疾病、固体 器官、骨髓和异种移植。 赞助商唐·西格尔博士和史蒂文·斯皮塔尼克博士的实验室， 提供独特和理想的环境，以便开展建议的 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。 Spitalnik博士是一位公认的红色特征专家 细胞糖类抗原/抗体的相互作用。总而言之，张博士的 赞助商是莱斯博士领导的输血医学部的一部分 西尔伯斯坦是候选人拟议的咨询委员会的成员，该委员会 最近成立了由NHLBI资助的专门研究中心 输血医学与生物学。与候选人提出的 分子建模和表面等离子激元领域的顾问 共鸣，张博士将获得技术和专业知识 为免疫血液学领域做出未来的独立贡献 临床科学家。(摘要结束)

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)