CAREER: Understanding the Molecular and Structural Composition of Aggressive Cancers using Deep Ultraviolet Spectroscopy and Imaging

转移被认为是导致癌症患者死亡的主要事件。不幸的是，我们根据原发肿瘤的指标来评估转移的相对风险的能力非常差。这项建议的目标是开发和应用一种新的方法来了解转移的原发肿瘤的分子和结构组成，以改善癌症预后。PI将开发一种光学显微镜技术-紫外线高光谱干涉显微镜，该技术探测细胞和组织在光谱的深紫外区的吸收和散射特性。这种方法的数据将为理解癌症中被破坏的分子的弥散和吸收特性提供前所未有的洞察力。最初的重点是黑色素瘤，但这种方法可以用来改善所有癌症的预后。这项工作有可能挽救许多人的生命，降低患者的发病率和医疗成本。PI将利用这一概念，即表观的“共同点”，包括代谢物、核形态和纳米结构的变化，可以在不同的患者中提供一套一致的标记物，唯一地识别侵袭性疾病。为了获得这些表型，他们将开发一种名为紫外线高光谱干涉(UHI)显微镜的新光学显微镜技术，该技术可以获得深紫外区(200 nm-400 nm)细胞和组织独特的内源色散、吸收和散射特性。这一光谱区域与干涉测量方法相结合，提供了对多种表型的前所未有的洞察，包括分子组成、亚细胞形态和纳米级结构。将对不同配置的城市热岛显微镜进行测试，以优化信噪比、成像速度和灵敏度。然后，该方法将被用来更好地了解在癌症中被破坏的内源性分子的分散和吸收特性。将对体外细胞、动物和人类组织活检样本进行分析，以确定侵袭性疾病的生物标志物。这项工作的结果将有助于为改进肿瘤分期的新方法铺平道路，从而改善临床结果。此外，这里开发的系统和方法可以适用于生物学和医学的其他领域，并成为生物学家和医学研究人员测试新假说的基本工具。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Metastasis is considered the principal event leading to death in individuals with cancer. Unfortunately, our ability to assess the relative risk of metastasis based on indicators from primary tumors is extremely poor. The goal of this proposal is to develop and apply a new method to understand the molecular and structural composition of primary tumors that metastasize to improve cancer prognosis. The PI will develop an optical microscopy technique, ultraviolet hyperspectral interferometric microscopy, that probes the absorptive and scattering properties of cells and tissues in the deep ultraviolet region of the spectrum. The data from this method will yield unprecedented insight into understanding the dispersive and absorptive properties of molecules that are disrupted in cancers. The initial focus is on melanoma but the approach can be used to improve prognosis of all cancers. This work has the potential to save many lives and reduce patient morbidity and healthcare costs.The PI will leverage the concept that phenotypical "common-denominators," including changes in metabolites, nuclear morphology, and nano-architecture, can provide a consistent set of markers across different patients that uniquely identify aggressive disease. To gain access to these phenotypes, they will develop a novel optical microscopy technique called ultraviolet hyperspectral interferometric (UHI) microscopy, which yields access to unique endogenous dispersive, absorptive and scattering properties of cells and tissues in the deep ultraviolet region of the spectrum (200 nm - 400 nm). This region of the spectrum combined with the interferometric approach offers unprecedented insight into a wide number of phenotypes, including molecular makeup, subcellular morphology, and nanometer-scaled structures. Different configurations of UHI microscopy will be tested to optimize the signal-to-noise ratio, imaging speeds, and sensitivity. Then the method will be used to gain a better understanding of the dispersive and absorptive properties of endogenous molecules that are disrupted in cancers. In-vitro cells, and animal and human tissue biopsies samples will be analyzed to identify biomarkers of aggressive disease. Results from this work will help pave the way for a new approach that improves tumor staging, and thus clinical outcome. In addition, the systems and methods developed here can be applicable to other areas of biology and medicine, and become fundamental tools for biologists and medical researchers to test novel hypotheses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.