Corrupted gene expression in cancer is largely driven by RNA-protein interactions that result in altered mRNA processing and translation. To explore RNA regulatory networks that drive cancer progression, my work has developed innovative tools that allow discovery of RNA binding proteins (RBPs), measurement of RBP- and ribosome-mRNA contacts at single-cell and single-molecule resolution, and site-directed editing/modification of specific target RNAs for therapeutic purposes. My CPRIT-funded program would integrate these approaches in order to develop powerful and nimble RNA-based cancer therapies. The 3 primary goals of the program are: 1) Establish a scalable one-pot approach for multiplexed...

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Corrupted gene expression in cancer is largely driven by RNA-protein interactions that result in altered mRNA processing and translation. To explore RNA regulatory networks that drive cancer progression, my work has developed innovative tools that allow discovery of RNA binding proteins (RBPs), measurement of RBP- and ribosome-mRNA contacts at single-cell and single-molecule resolution, and site-directed editing/modification of specific target RNAs for therapeutic purposes. My CPRIT-funded program would integrate these approaches in order to develop powerful and nimble RNA-based cancer therapies. The three primary goals of the program are: 1) Establish a scalable one-pot approach for multiplexed identification of the RNA-targets of dozens translational-regulatory RBPs recently identified to confer cancer cell survival. 2) Develop a high-throughput platform for evaluating cancer therapeutics, including directly modified RNA-based therapeutics, that modulate RNA-processing and translation. 3) Engineer in-vitro reagents for coupling spatial transcriptomics to RNA-protein-interaction- and ribosome-profiling in patient samples. This work will uncover the mechanisms underlying pathologies for cancers with disrupted RNA processing and translation phenotypes. This mechanistic understanding will drive innovation of RNA-based therapeutic modalities, including mRNA prophylactic cancer vaccines, that we will develop at the CPRIT-funded RNA Core at Houston Methodist Research Institute. The RNA Core is uniquely positioned to evaluate these RNA therapeutic candidates with access to a small-scale manufacturing process for research and clinical grade mRNA, as well as pre-clinical GLP testing and regulatory assistance, and a first-in-man clinical trial facility.

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