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

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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.