MECHANISMS OF OSTEOLYTIC BONE DESTRUCTION

描述(申请人的描述)：应聘者毕业于 波多黎各大学医学院，并已完成了 得克萨斯大学健康科学学院血液学/肿瘤学奖学金 并计划在学术医学和医学领域的职业生涯 基础研究。这一奖项将用于发展候选人的研究 细胞和分子生物学技能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……里面 与鲁德曼博士合作，这位候选人开发出了第一个模型 在SCID小鼠中发现人类骨髓瘤骨病，并将利用该模型 探讨骨髓瘤骨病的发病机制。 破骨细胞介导的骨破坏是导致 患者患有骨髓瘤，但其发病机制尚不清楚。假设 将在目前的提议中测试的是骨髓瘤细胞产生新的 体内刺激破骨细胞形成和骨吸收的因子。 这位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，将被测序并鉴定为 如下：(A)利用RT-PCR，该因子将在 骨髓瘤活体模型受累骨髓标本的RNA 多发性骨髓瘤患者的疾病和新鲜分离的骨髓； 利用原位杂交和免疫细胞化学技术， 表达这一因子的细胞类型将被确定。此外， 研究人员将确定该因子是否由正常的CD19+B表达 通过筛选细胞先前准备的CD19+B细胞库；(C) 将制备重组蛋白；(D)重组蛋白将 测试其促进人骨髓破骨细胞形成的能力 骨器官培养中的培养和骨吸收。调查人员将 也在继续努力从他们的骨髓瘤表达文库中克隆 来自其他五个阳性表达池的破骨细胞刺激因子 在骨髓培养中刺激破骨细胞的形成。

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.