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

本项目旨在建立细胞生长速率、细胞代谢与细胞核结构之间的定量关系，并进一步评价其在肿瘤侵袭性测定中的应用。首先获得由细胞代谢和细胞核结构控制的细胞生长动力学，然后通过细胞系实验进行测试和验证。将利用定量相显微镜和化学显微镜对ATP的产生和核结构进行成像，从而建立一种快速捕捉细胞生长速率的新方法。该方法的有效性将通过组织切片测量来评估区分侵袭性前列腺癌和非侵袭性前列腺癌的效果。功能和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，如前列腺肿瘤，可以有两种不同的病程——惰性或高度侵袭性，如果不治疗就会导致死亡。临床医生和患者每天必须选择一种主要的治疗方式，从手术，伴随发病率和生活质量下降到观察等待，延迟治疗有生命危险。需要在诊断时进行准确的癌症风险分层，以识别高危患者，从而选择最佳治疗策略，提高患者的生活质量，减轻经济负担。定量生长速度作为肿瘤侵袭性的客观指标将满足这一迫切需求。这笔资金还将支持首席研究员继续他在初级本科大学的研究与教育结合的努力，并进一步发展用于量化生物系统静态结构和动态过程的光学技术以及揭示癌症物理学的前沿研究。招收物理、工程、生物专业本科学生。将鼓励医学预科学生和少数民族学生参加。将特别强调从本科生中培养和训练未来的科学家和工程师。将积极进行研究成果的传播和技术转让。PI将开发一个最小的粗粒度模型，明确表达细胞代谢和核结构方面的细胞生长速度。该模型捕捉了细胞生长的主要特征，特别是在能量通量和DNA复制的背景下，目的是以一种简单但实验可验证的方式理解细胞繁殖的复杂过程。这将有助于定量地了解细胞生长的潜在机制。定量生长速度作为肿瘤侵袭性和风险分层的客观指标，将在肿瘤筛查、诊断和治疗决策中得到广泛应用。

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.