MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7064593
• 负责人: ADAOBI I NWANESHIUDU
• 金额: $ 2.98万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064593
• 关键词: T cell receptor; T lymphocyte; antigen presentation; autoantibody; cell line; clinical research; clone cells; disease /disorder classification; embryo /fetus antigen; enzyme linked immunosorbent assay; gene expression; human subject; hybrid antibody; immunocytochemistry; in situ hybridization; microarray technology; molecular pathology; pathologic process; polymerase chain reaction; predoctoral investigator; prognosis; proteomics; skin; systemic scleroderma

DESCRIPTION (provided by applicant): Systemic Sclerosis (SSc) is a disease of unknown etiology characterized by fibrosis, small vessel fibrointimal proliferation, and autoantibody production; all possibly resulting from involvement of T-cells. Organ complications can be extensive, significantly increasing morbidity and mortality. Previous studies from our laboratory show evidence of oligoclonal T-cells proliferation in the skin and peripheral blood of SSc patients, in response to currently unidentified antigens. Putative antigens include microchimeric cells, CMV and DNA topoisomerase-l. The project aims to determine the specific role(s) T-cells play in SSc pathogenesis, and potential predictor molecular signatures that predispose patients to the complications of the disease. Specific aims are to, 1)-determine the origin of clonally-expanded gamma/delta T-cells, using in-situ hybridization; 2)- identify antigens recognized by these clonally-expanded T-cells in skin biopsies and peripheral blood samples from maternal and offspring SSc patients, via transducing full-length TCR chain transcripts into beta chain TCR-negative mutant Jurkat T-cells or delta-chain TCR-negative mutant MOLT-13 T-cells and other appropriate cell lines; 3)-Use DNA microarray to assess risks for complications; and relate to sex and race.

描述（由申请人提供）：系统性硬化症（SSC）是一种未知病因的疾病，其特征是纤维化，小血管纤维纤维增殖和自身抗体产生；所有这些都可能是由于T细胞的参与而产生的。器官并发症可能广泛，大大提高发病率和死亡率。我们实验室的先前研究表明，SSC患者的皮肤和外周血中的寡克隆T细胞增殖的证据，响应当前未识别的抗原。假定的抗原包括微chimeric细胞，CMV和DNA拓扑异构酶-L。该项目旨在确定特定的T细胞在SSC发病机理中的特定作用，并确定使患者患有疾病并发症的潜在预测分子特征。具体目的是使用原位杂交确定克隆膨胀的γ/delta t细胞的起源； 2） - 通过将全长的TCR链转录到β链TCR链TCR链TCR-negkat T-Cells或Delta-crchain TCR-negation Mutant Molts-13 TCR-13 TCELLS MOLTS-13 TCELLS-13 TCELLS-13 TCELLS; 3） - 使用DNA微阵列评估并发症的风险；并与性与种族有关。