Imaging nuclear architecture at nanoscale for cancer prognosis
Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Current clinical gold standard for diagnosing cancer and predicting cancer progression risk relies on the evaluation of nuclear morphology by a trained pathologist using bright-field microscope, which has very limited performance in patients without the presence of clinically significant lesions such as patients with ulcerative colitis or atypical hyperplasia in breast. To address this highly unmet clinical need, we aim to answer two major questions: First, given that nuclear architecture plays an important role in regulating the function of genome and epigenome in cancer progression, does the genome-level high-order nuclear architecture at nanoscale provide earlier and more accurate prediction of cancer progression? Second, if it does, can we develop clinically applicable instrument to interrogate nanoscale nuclear architecture with a high throughput to better inform the clinical decision-making? Our laboratory developed a new imaging technique based on low-coherence spectral interferometry, capable of high-throughput mapping of nuclear architecture at a nanoscale sensitivity on label-free tissue and cells, with a goal to identify new imaging-based markers to predict cancer progression and understand the transformation of nuclear architecture in carcinogenesis. We demonstrated that nanoscale nuclear architecture exhibit distinct imaging features characteristic of early cancer development before characteristic nuclear morphological changes can be visualized with conventional light microscopy. We are also using super-resolution fluorescence nanoscopy for mechanistic understanding of alterations in high-order genome architecture during malignant transformation. Nanoscale nuclear architecture imaging is a potential new tool for personalized cancer risk assessment, to predict the individual’s cancer progression risk assessment at a pre-cancerous stage to reduce unnecessary treatment.