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

职业：利用深紫外光谱和成像了解侵袭性癌症的分子和结构组成

• 批准号: 1752011
• 负责人: Francisco Robles
• 金额: $ 50万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1752011&HistoricalAwards=false
• 关键词: CAREER; Understanding; Molecular; Structural; Composition

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.

转移被认为是导致癌症个体死亡的主要事件。不幸的是，我们根据原发性肿瘤的指标评估转移相对风险的能力非常差。该提案的目标是开发和应用一种新的方法来了解转移的原发性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，紫外高光谱干涉显微镜，探测光谱的深紫外区细胞和组织的吸收和散射特性。这种方法的数据将产生前所未有的洞察力，以了解在癌症中被破坏的分子的分散和吸收特性。最初的重点是黑色素瘤，但该方法可用于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将利用表型“共同标记物”的概念，包括代谢物，核形态和纳米结构的变化，可以提供一套一致的标记物，在不同的患者中，唯一识别侵袭性疾病。为了获得这些表型，他们将开发一种称为紫外高光谱干涉（UHI）显微镜的新型光学显微镜技术，该技术可以在光谱的深紫外区（200 nm - 400 nm）获得细胞和组织独特的内源性色散，吸收和散射特性。光谱的这一区域与干涉方法相结合，提供了前所未有的洞察到广泛的表型，包括分子组成，亚细胞形态和纳米尺度的结构。将测试不同配置的UHI显微镜，以优化信噪比，成像速度和灵敏度。然后，该方法将用于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。将分析体外细胞以及动物和人体组织活检样本，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善肿瘤分期的新方法铺平道路，从而改善临床结果。此外，本研究所开发的系统和方法也可应用于生物学和医学的其他领域，成为生物学家和医学研究人员检验新假设的基本工具。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Quantitative phase imaging with epi-mode illumination for fiber-optic endoscopy

用于光纤内窥镜的外延模式照明定量相位成像

• DOI: 10.1117/12.2546402
• 发表时间: 2020
• 期刊: Quantitative Phase Imaging VI
• 作者: Guang, Zhe;Ledwig, Patrick B.;Casteleiro Costa, Paloma;Robles, Francisco E.
• 通讯作者: Robles, Francisco E.

Deep UV microscopy of prostate cancer tissue

前列腺癌组织的深紫外显微镜

• DOI: 10.1117/12.2546200
• 发表时间: 2020
• 期刊: and Tissues XVIII
• 作者: Soltani, Soheil;Ojaghi, Ashkan;Kludze, Atsutse;Robles, Francisco E.
• 通讯作者: Robles, Francisco E.

Analysis of Melanin Structure and Biochemical Composition in Conjunctival Melanocytic Lesions Using Pump–Probe Microscopy

使用泵探针显微镜分析结膜黑素细胞病变中的黑色素结构和生化成分

• DOI: 10.1167/tvst.8.3.33
• 发表时间: 2019
• 期刊: Translational Vision Science & Technology
• 影响因子: 3
• 作者: Robles, Francisco E.;Deb, Sanghamitra;Vajzovic, Lejla;Vora, Gargi K.;Mruthyunjaya, Prithvi;Warren, Warren S.
• 通讯作者: Warren, Warren S.

Ultraviolet multi-spectral microscopy using iterative phase-recovery from chromatic aberrations

使用色差迭代相位恢复的紫外多光谱显微镜

• DOI: 10.1117/12.2508972
• 发表时间: 2019
• 期刊: Quantitative Phase Imaging V
• 作者: Ojaghi, Ashkan;Robles, Francisco E.;Popescu, Gabriel;Park, YongKeun
• 通讯作者: Park, YongKeun

3D refractive index tomography with quantitative oblique back-illumination microscopy

• DOI: 10.1117/12.2544328
• 发表时间: 2020-02
• 作者: P. Ledwig;Francisco E. Robles