Nanotechnology Linking Biomarkers with Cancer Behavior

描述(申请人提供)：该BRP申请旨在通过整合佐治亚理工学院(佐治亚州亚特兰大)的生物工程优势、CSRI(马萨诸塞州沃本)的光谱成像专业知识以及埃默里大学医学院(泌尿学、病理学、放射肿瘤学、Winship癌症研究所和佐治亚州亚特兰大VA医院)的癌症生物学和临床肿瘤学经验，建立一个高度协作的多学科癌症纳米技术计划。这一合作伙伴关系由八个科学、工程和临床系的教师参与，并由著名的科学顾问委员会(SAB)提供建议，包括生物工程、生物信息学、肿瘤生物学、生物分析化学、系统生物学、血液学/肿瘤学、病理学和泌尿学方面的广泛专业知识。其广泛和长期的目标是开发生物医学纳米技术、生物分子工程和生物信息学工具，将癌症的分子标记(生物标记物)和宿主微环境与癌症行为和临床结果联系起来。这项拟议的研究广泛适用于许多类型的恶性肿瘤，如乳腺癌、结直肠癌和淋巴瘤，但将特别关注人类前列腺癌的生物学行为及其临床致命表型。这一关注的一个令人信服的原因是前列腺癌在人类肿瘤学中提出了许多独特的挑战和机会。它的广泛发生(今年在美国约有22万例新病例)，自然病史长的倾向，高度异质性和多灶性的组织病理学，以及向激素非依赖性的进展仍然鲜为人知。面对这一现实，我们建议开发先进的纳米颗粒技术(如分子信标、半导体量子点和增强型拉曼探针)，用于对完整的癌细胞或组织标本上的生物标记物进行超灵敏和多重分析。与目前的分子图谱技术不同，编码纳米颗粒探针的使用允许将传统病理学和癌症生物学与敏感的分子分析无缝结合，这是贯穿整个拟议研究的一个中心主题。在这一BRP的背后，是成功地合作吸引联合研究资助的高级调查人员的良好记录。此外，佐治亚理工学院和埃默里大学于1997年联合成立的生物医学工程系为研究合作提供了一个不同寻常的机会，可以将生物工程技术和发现带入医学，反之亦然。如果获得资金，这个癌症纳米技术项目将设在温希普癌症研究所，这是一座占地280,000平方英尺的新癌症研究和护理大楼，位于埃默里校区，拥有真正出色的合作和转化型癌症研究环境。除了癌症生物学和生物标记物的基本知识外，这一伙伴关系预计将产生至少三个实际成果：(A)一个将分子签名与癌症生物学和临床结果联系起来的数据库；(B)用于癌症分子图谱的生物结合纳米颗粒；(C)多路光谱成像显微镜和软件。

DESCRIPTION (provided by applicant): This BRP application aims to establish a highly collaborative and multidisciplinary cancer nanotechnology program by integrating the bioengineering strengths of Georgia Tech (Atlanta, GA), the spectral imaging expertise of CSRI (Woburn, MA), and the cancer biology and clinical oncology experiences of Emory University School of Medicine (Urology, Pathology, Radiation Oncology, Winship Cancer Institute, and the VA Hospital, Atlanta, GA). With faculty participation from eight science, engineering, and clinical departments, and advised by a prominent Scientific Advisory Board (SAB), this Partnership incorporates broad expertise in bioengineering, bioinformatics, tumor biology, bioanalytical chemistry, systems biology, hematology / oncology, pathology, and urology. Its broad and long-term goal is to develop biomedical nanotechnology, biomolecular engineering, and bioinformatics tools for linking molecular signatures (biomarkers) of cancer and the host microenvironment with cancer behavior and clinical outcome. The proposed research is broadly applicable to many types of malignant tumors such as breast cancer, colorectal carcinoma, and lymphoma, but a particular focus will be placed on the biological behavior of human prostate cancer and its clinically lethal phenotypes. A compelling reason for this focus is that prostate cancer presents a number of unique challenges and opportunities in human oncology. Its widespread occurrence (about 220,000 new cases this year in the US), tendency for a long natural history, highly heterogeneous and multi-focal histopathology, and progression to hormone independence are still poorly understood. Faced with this reality, we propose to develop advanced nanoparticle technologies (e.g., molecular beacons, semiconductor quantum dots, and enhanced Raman probes) for ultrasensitive and multiplexed profiling of biomarkers on intact cancer cells or tissue specimens. In contrast to current molecular-profiling technologies, the use of encoded nanoparticle probes allows a seamless integration of traditional pathology and cancer biology with sensitive molecular analysis, a central theme that runs across the entire proposed research. Underlying this BRP is a strong track record of the senior investigators who have worked together successfully in attracting joint research grants. In addition, the Department of Biomedical Engineering, which was jointly established in 1997 by Georgia Tech and Emory University, has presented an unusual opportunity for research collaboration to bring bioengineering technologies and discoveries into medicine and vice versa. If funded, this cancer nanotechnology program will be housed in the Winship Cancer Institute, a new 280,000 sq ft cancer research and care building located on the Emory Campus and with a truly outstanding environment for collaborative and translational cancer research. In additional to basic knowledge on cancer biology and biomarkers, this Partnership is expected to yield at least three practical outcomes: (a) a database linking molecular signatures with cancer biology and clinical outcome, (b) bioconjugated nanoparticles for molecular profiling of cancer, and (c) muiltiplexed spectral imaging microscopes and software.