An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection

项目摘要 萨拉特-桑切斯女士将进行的补充的主要目标是设计，建立和验证 人原发性肿瘤和人骨髓的集成“器官芯片”平台。这很重要 因为：1）所有肿瘤都参与免疫系统，因此骨髓（免疫系统的主要来源） 细胞）;和2）广泛的肿瘤在进展过程中利用骨髓对肿瘤有利 和等待时间（例如，乳腺癌）。研究里程碑包括：1）证明熟练掌握所有步骤， 软光刻，包括CAD设计、光刻和PDMS器件构造; 2）演示 熟练掌握细胞培养技术;以及在体外骨髓和癌症模型中的加载和培养。 3）定量微流体装置内白细胞的数量、表型和位置 对一系列乳腺癌细胞系应答;和4）对一系列乳腺癌细胞系的数量、表型和位置进行定量 乳腺癌细胞系的微流控装置。除了研究里程碑外， 我将努力完成与职业发展相关的一系列里程碑，包括：1）完成 3门选修课程; 2）指导本科研究人员; 3）在全国会议上介绍她的工作; 4） 在同行评议的存档期刊上发表她的作品; 5）提交她自己的独立F31 应用程序.完成这些里程碑将使萨拉特-桑切斯女士为独立和 有影响力的科学事业。

PROJECT SUMMARY The primary goal of the supplement to be carried out by Ms. Zarate-Sanchez is to design, build, and validate an integrated “organ-on-a-chip” platform of human primary tumor and human bone marrow. This is important because: 1) all tumors engage the immune system, and thus the bone marrow (primary source of immune cells); and 2) a wide range of tumors co-opt the bone marrow to the advantage of the tumor during progression and latency (e.g., breast cancer). The research milestones include: 1) demonstrate proficiency in all steps of soft lithography, including CAD design, photolithography, and PDMS device construction; 2) demonstrate proficiency in cell culture techniques; and loading and culture of in vitro bone marrow and cancer models in the microfluidic device; 3) quantify number, phenotype, and location of the leukocytes within the microfluidic device in response to a series of breast cancer cell lines; and 4) quantify number, phenotype, and location of a series of breast cancer cells lines in the microfluidic device. In addition to the research milestones, the supplement will seek to accomplish a series of milestones associated with her career development including: 1) completing 3 elective courses; 2) mentoring undergraduate researchers; 3) presenting her work at a national meeting; 4) publishing her work in a peer-reviewed archived journal(s); and 5) submitting her own independent F31 application. Accomplishing these milestones will prepare Ms. Zarate-Sanchez for an independent and impactful scientific career.