CAREER: Understanding the Molecular and Structural Composition of Aggressive Cancers using Deep Ultraviolet Spectroscopy and Imaging

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Metastasis is considered the principal event leading to death in individuals with cancer. Unfortunately, our ability to assess the relative risk of metastasis based on indicators from primary tumors is extremely poor. The goal of this proposal is to develop and apply a new method to understand the molecular and structural composition of primary tumors that metastasize to improve cancer prognosis. The PI will develop an optical microscopy technique, ultraviolet hyperspectral interferometric microscopy, that probes the absorptive and scattering properties of cells and tissues in the deep ultraviolet region of the spectrum. The data from this method will yield unprecedented insight into understanding the dispersive and absorptive properties of molecules that are disrupted in cancers. The initial focus is on melanoma but the approach can be used to improve prognosis of all cancers. This work has the potential to save many lives and reduce patient morbidity and healthcare costs.The PI will leverage the concept that phenotypical "common-denominators," including changes in metabolites, nuclear morphology, and nano-architecture, can provide a consistent set of markers across different patients that uniquely identify aggressive disease. To gain access to these phenotypes, they will develop a novel optical microscopy technique called ultraviolet hyperspectral interferometric (UHI) microscopy, which yields access to unique endogenous dispersive, absorptive and scattering properties of cells and tissues in the deep ultraviolet region of the spectrum (200 nm - 400 nm). This region of the spectrum combined with the interferometric approach offers unprecedented insight into a wide number of phenotypes, including molecular makeup, subcellular morphology, and nanometer-scaled structures. Different configurations of UHI microscopy will be tested to optimize the signal-to-noise ratio, imaging speeds, and sensitivity. Then the method will be used to gain a better understanding of the dispersive and absorptive properties of endogenous molecules that are disrupted in cancers. In-vitro cells, and animal and human tissue biopsies samples will be analyzed to identify biomarkers of aggressive disease. Results from this work will help pave the way for a new approach that improves tumor staging, and thus clinical outcome. In addition, the systems and methods developed here can be applicable to other areas of biology and medicine, and become fundamental tools for biologists and medical researchers to test novel hypotheses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.