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Research: Hua Shi
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The fundamental question addressed in my laboratory is how to achieve facile control over biological processes in vivo. The focus of our research projects is a forward engineering approach to cancer drug discovery and development. Cancer results after many genetic and epigenetic changes in the cell, and multiple activated oncogenes are often required to maintain the oncogenic status and viability of cancer cells. We seek to identify and to validate combinations of drug targets by modulating the function of many gene products in different pathways with temporal and spatial control in tissue culture cells or animals. One set of tools that is being developed and applied is RNA-based reagents and aptamers, from which, self-assembled supramolecular aggregates and synthetic gene circuits are created according to quantitative models, and used to probe and control protein functions in a scale-free regulatory network. Besides target validation,such “genetic applets” can be utilized directly as therapeutic agents. In a separate but related area of interest, we are also developing novel anti-viral strategies using a similar approach.