MULTI-PHOTON IMAGING OF ACTIN FILAMENT FORMATION AND MITOCHONDRIAL ENERGETICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 PI将开发多光子(MPM)光学成像方法，系统地研究嵌入在各种3D ECM中的人类胶质母细胞瘤多形球体。这些实验性的肿瘤模型系统被用来模拟体内的胶质瘤。利用还原烟酰胺腺嘌呤二核苷酸(NADH)和氧化黄素腺嘌呤二核苷酸(FAD)的固有细胞荧光，建立MPM比率氧化还原荧光法来研究线粒体的能量代谢。将这些发现与使用染料对线粒体膜的评估相结合，并结合线粒体信号观察F-肌动蛋白的分布，将有助于更好地理解细胞外基质如何改变恶性胶质瘤细胞的生长、分化和代谢状态。 开发的成像方法将帮助癌症研究人员研究关键的癌症特性，如细胞存活和转移，并可以准确测量肿瘤对治疗的反应。所提出的研究将有助于目前治疗多形性胶质母细胞瘤的方法和预后。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PI will be developing multiphoton (MPM) optical imaging methods to systematically study human glioblastoma multiform spheroids embedded in various 3D ECMs. These experimental cancer model systems are used to mimic the in vivo gliomas. An MPM ratiometric redox fluorometry method based on intrinsic cellular fluorescence from reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) to study mitochondrial energy metabolism will be developed by the PI. Coupling these finding with the evaluations of mitochondrial membrane using a dye and visualizing F-actin distribution in conjunction with mitochondrial signals will furnish a better understanding on how ECM alters the growth, differentiation and metabolic states of the malignant glioma cells. The imaging methods developed will help cancer investigators to study key cancer properties such as cell survival and metastasis and can allow accurate measurements of tumor response to treatments. The studies proposed will benefit current therapies and prognosis for glioblastoma multiform.