Mentored Quantitative Research Career Development Award

描述（由申请人提供）：本“导师定量研究发展奖”将帮助工程师候选人成为生物学家。它将通过参加课程来获得生物学/医学的基础知识，并通过指导研究发展相关的研究技能来实现。所选课程将包括生物医学基础和高级课程的核心课程。生物医学研究经验将通过导师和共同导师实验室的实验室轮岗获得。指导的研究是开发一个平台来浓缩和富集急性白血病细胞，以检测微小残留病（MRD）。MRD是指在治疗期间或治疗后患者处于缓解期（无疾病症状或体征）时仍存在残留在患者体内的恶性细胞。目前的基准方法对检测外周血中所有残留的肿瘤细胞不够敏感。因此，一个具有更高灵敏度的平台将是可取的，因为MRD可以区分那些需要强化和潜在毒性更大的治疗的人。该项目的具体目标是：(1)设计和制造一种富集白血病细胞的装置；(2)利用与急性淋巴细胞白血病细胞特异性结合的适配体，证明了该装置中白血病细胞的富集；(3)通过临床样本白血病细胞分析和MRD检测验证平台技术。本研究的意义在于以下几个方面。首先，提出的研究将导致一个平台，快速和有效的富集急性白血病细胞。该平台将提供一种可测量的方法来确定是否需要任何额外的化疗；这将给白血病患者带来巨大的好处，因为可以避免不必要的毒性治疗。其次，该平台可以很容易地用于富集其他癌症的稀有循环细胞。这些罕见肿瘤细胞的分离可以为早期癌症筛查和医学诊断提供机会。第三，这项研究将推动癌症生物学、生物医学工程和微纳米技术领域的发展。

DESCRIPTION (provided by applicant): This "Mentored Quantitative Research Development Award" will facilitate the candidate, an engineer, to become a biologist. It will be achieved by taking courses to gain fundamental knowledge in biology/medicine and developing relevant research skills via mentored research. The selected courses will include core courses encompassing the fundamentals of biomedical sciences and advanced courses. Biomedical research experience will be obtained through lab rotations in the mentor's and co-mentor's laboratories. The mentored research is to develop a platform to concentrate and enrich acute leukemia cells for detection of minimal residual disease (MRD). MRD refers to the presence of residual malignant cells that remain in the patient during treatment or after treatment when the patient is in remission (no symptoms or signs of disease). The current benchmark method is not sufficiently sensitive for detecting all remaining tumor cells in peripheral blood. As a result, a platform with a higher sensitivity will be desirable since MRD can distinguish those who need intensive and potentially more toxic therapy from those who do not. The specific aims of this project are to (1) design and fabricate a device for enrichment of leukemia cells; (2) demonstrate the enrichment of leukemia cells in the device using aptamers with specific binding to acute lymphoblastic leukemia cells; and (3) validate the platform technology by analyzing leukemia cells in clinical samples and detect MRD. The significance of the research lies in the following aspects. First, the proposed research will lead to a platform for a rapid and efficient enrichment of acute leukemia cells. The platform will offer a measureable approach to determine if any additional chemo-therapy is needed; this will bring significant benefits to leukemia patients since unnecessary toxic therapy can be avoided. Second, the platform can be easily adapted for enrichment of rare circulating cells of other cancers. Isolation of these rare tumor cells could offer an opportunity for early-stage cancer screening and medical diagnostics. Third, the proposed research will advance the fields of cancer biology, biomedical engineering, and micro-nanotechnologies.