RUI: Cell Growth Laws and Quantitative Microscopy for Cancer Aggressiveness Imaging

RUI：细胞生长规律和癌症侵袭性成像的定量显微镜

• 批准号: 1920617
• 负责人: Min Xu
• 金额: $ 17.68万
• 依托单位: CUNY Hunter College
• 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: 2018-12-05 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1920617&HistoricalAwards=false
• 关键词: RUI; Cell; Growth; Laws; Quantitative

The project aims to develop and establish a quantitative relation between the cell growth rate, cellular metabolism, and the cellular nuclear structure and further evaluate its application in determination of cancer aggressiveness. Cell growth kinetics controlled by cellular metabolism and nuclear structure will be first obtained, which will then be tested and validated by cell line experiments. A novel approach of snapshotting cell growth rate will be developed through imaging ATP production and nuclear structure with quantitative phase and chemometric microscopy. The efficacy of the approach will be assessed in distinguishing aggressive prostate cancer from non-aggressive ones with tissue section measurements. The interplay between function and structure is one central problem in cancer research. This work will provide new insights into understanding this complex interplay. Cancers, such as prostate tumors, can take two distinct disease courses -- indolent or highly aggressive, leading to death if not treated. Clinicians and patients daily must choose a primary treatment modality from surgery, accompanying morbidity and compromised quality of life to watchful waiting, risking life with delayed treatment. Accurate risk stratification of cancer at time of diagnosis to identify those patients at high risk is critically needed to choose the optimal treatment strategy, enable higher life quality for the patient, and reduce the economic burden. The quantitative growth rate as an objective marker for cancer aggressiveness will address this urgent need. The funding will also support the PI to continue his effort in integrating research and education in a primary undergraduate university, and further the cutting-edge research on developing optical techniques for quantifying the static structure and dynamic processes in biological systems and revealing physics of cancer. Undergraduate students will be recruited from Physics, Engineering and Biology majors. Premedical and minority students will be encouraged to participate. Special emphasis will be placed on nurturing and training future scientists and engineers from undergraduate students. Dissemination of research results and technical transfer will be actively pursued.The PI will develop a minimal coarse-grained model expressing explicitly the cell growth rate in terms of cellular metabolism and nuclear structure. This model captures the main features of the growth of a cell, especially in the context of energy fluxes and DNA replication, with the purpose of understanding the complex processes of cell reproduction in a simple yet experimentally verifiable way. This should shed quantitative insight into the underlying mechanisms of cell growth. The quantitative growth rate as an objective marker for cancer aggressiveness and risk stratification will find wide applications in cancer screening, diagnosis, and decision making in cancer treatment.

该项目旨在在细胞生长速率，细胞代谢和细胞核结构之间建立和建立定量关系，并进一步评估其在确定癌症侵袭性中的应用。由细胞代谢和核结构控制的细胞生长动力学将首先获得，然后通过细胞系实验对其进行测试和验证。快照细胞生长速率的新方法将通过具有定量相和化学计量显微镜的成像ATP产生和核结构来开发。该方法的功效将在区分侵袭性前列腺癌和具有组织段测量的非侵略性癌症方面进行评估。功能与结构之间的相互作用是癌症研究中的一个核心问题。这项工作将为理解这种复杂的相互作用提供新的见解。癌症，例如前列腺肿瘤，可以接受两种不同的疾病课程 - 懒惰或高度侵略性，如果不治疗，导致死亡。临床医生和患者每天必须从手术中选择主要的治疗方式，伴随发病率，生活质量受损，以期待等待，并冒着延迟治疗的生命危险。在诊断时，癌症的准确风险分层以确定那些处于高风险的患者以选择最佳治疗策略，为患者提供更高的生活质量并减轻经济负担。定量增长率是癌症侵略性的客观标志物，将满足这一迫切需求。这项资金还将支持PI继续他在小学大学中将研究和教育整合在一起的努力，并进一步开发有关量化生物系统中静态结构和动态过程并揭示癌症物理学的静态结构和动态过程的尖端研究。本科生将从物理，工程和生物学专业的专业中招募。将鼓励有训练和少数族裔学生参加。特别重点将放在培养和培训本科生的未来科学家和工程师。将积极追求研究结果和技术转移的传播。PI将开发一个最小的粗粒模型，以细胞代谢和核结构来明确表达细胞生长速率。该模型捕获了细胞生长的主要特征，尤其是在能量通量和DNA复制的背景下，目的是以一种简单但可以实验性的可验证方式理解细胞再现的复杂过程。这应该对细胞生长的潜在机制进行定量洞察力。定量生长速率是癌症侵略性和风险分层的客观标志物，将在癌症治疗中发现广泛的应用。