MECHANISMS OF OSTEOLYTIC BONE DESTRUCTION

描述（申请人的描述）：候选人是一个毕业生的 波多黎各大学医学院，并已完成学术 德克萨斯大学健康科学系血液学/肿瘤学研究员 中心（UTHSC）于1995年，并计划在学术医学和 基础研究 该奖项将用于发展候选人的研究 细胞和分子生物学技能，以及新型破骨细胞的筛选 在高度监督的研究环境中的刺激因素。 在 与Roodman博士合作，候选人开发了第一个模型 在SCID小鼠中的人类骨髓瘤骨疾病，并将使用该模型， 研究骨髓瘤骨病的潜在机制。 破骨细胞介导的骨破坏是骨关节炎发病的主要原因。 骨髓瘤患者，但其发病机制尚不清楚。 的假设 将在目前的建议是测试骨髓瘤细胞产生新的 刺激破骨细胞形成和骨吸收的体内因子。 该候选人最近克隆了一种新的破骨细胞刺激因子， 由骨髓瘤细胞表达，其将被测序并表征为 以下：（a）使用RT-PCR，该因子的表达将在 来自骨髓瘤骨体内模型的相关骨髓样本的RNA 疾病和来自多发性骨髓瘤患者的新鲜分离的骨髓;（B） 应用原位杂交和免疫细胞化学技术， 将确定表达该因子的细胞类型。 此外该 研究者将确定该因子是否由正常的CD 19 + B表达 通过筛选先前制备的CD 19 + B细胞文库， 将制备重组蛋白;（d）将制备重组蛋白， 测试了它在人类骨髓中增强破骨细胞形成的能力 培养物和骨器官培养物中的骨吸收。 调查人员将 他们还继续努力从骨髓瘤表达文库中克隆 其他5个阳性表达池中的破骨细胞刺激因子 刺激骨髓培养中破骨细胞的形成。

DESCRIPTION (Applicant's Description): The candidate is a graduate of the University of Puerto Rico School of Medicine and has completed an academic Fellowship in Hematology/Oncology at the University of Texas Health Science Center (UTHSC) in 1995 and plans to pursue a career in academic medicine and basic research. This award will be used to develop the candidate's research skills in cellular and molecular biology, and screening of novel osteoclast stimulatory factors in a highly supervised research setting. In collaboration with Dr. Roodman, the candidate has developed the first model of human myeloma bone disease in SCID mice and will use this model to investigate the mechanisms underlying myeloma bone disease. Osteoclast-mediated bone destruction is the major cause of morbidity in patients with myeloma, but its pathogenesis is unclear. The hypothesis that will be tested in the current proposal is that myeloma cells produce novel factors in vivo that stimulate osteoclast formation and bone resorption. The candidate has recently cloned a novel osteoclast stimulatory factor, expressed by myeloma cells, that will be sequenced and characterized as follows: (a) Using RT-PCR, expression of this factor will be confirmed in RNA from involved marrow samples from their in vivo model of myeloma bone disease and freshly isolated marrow from patients with multiple myeloma; (b) Using the techniques of in situ hybridization and immunocytochemistry, the cell types expressing this factor will be determined. In addition, the investigators will determine if this factor is expressed by normal CD19+ B cells by screening their previously prepared CD19+ B cell library; (c) The recombinant protein will be prepared; (d) The recombinant protein will be tested for its capacity to enhance osteoclast formation in human marrow cultures and bone resorption in bone organ cultures. The investigators will also continue their efforts to clone from their myeloma expression library osteoclast stimulatory factors from the other five positive expression pools that stimulate osteoclast formation in marrow cultures.