Rewiring of RNA processing and translation is one of the most common hallmarks of cancer. Indeed, systematic proteogenomics cancer initiatives (ex. CPTAC) demonstrate that RNA levels frequently do not correlate (nor explain) protein levels and function in patient tumors and cancer models. This has major consequences for both our understanding of the (de)regulation of gene expression in cancer as well as precision cancer diagnosis and treatment. However, the molecular mechanisms that underpin deregulated RNA processing and translation in cancer are poorly understood.

In this proposal, I describe the development of a research laboratory in the Therapeutic Innovation Center at the Baylor Colleg...

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Rewiring of RNA processing and translation is one of the most common hallmarks of cancer. Indeed, systematic proteogenomics cancer initiatives (ex. CPTAC) demonstrate that RNA levels frequently do not correlate (nor explain) protein levels and function in patient tumors and cancer models. This has major consequences for both our understanding of the (de)regulation of gene expression in cancer as well as precision cancer diagnosis and treatment. However, the molecular mechanisms that underpin deregulated RNA processing and translation in cancer are poorly understood.

In this proposal, I describe the development of a research laboratory in the Therapeutic Innovation Center at the Baylor College of Medicine focused on integrating experimental genomic and bioinformatic tools to understand how deregulation of translation drives breast cancer.

My lab will focus on three primary research goals:

1) To identify RNA binding protein (RBP):RNA target programs that drive altered proteomes in breast cancer by exploiting our newly developed large-scale RBP-target profiling platforms

2) To leverage new technologies to discover microRNA regulatory networks that drive altered gene expression, breast cancer pathogenesis, and therapeutic response

3) To develop technology platforms that enable profiling of RNA processing regulation in primary human tumors Through this work, we will achieve a global understanding of RBP and microRNA regulatory networks that drive altered translation in breast cancer.

In addition to yielding novel insights into basic mechanisms of gene regulation, this framework of combining computational and experimental approaches to enable a broad and unbiased mapping of RBP-microRNA regulatory networks will provide a new paradigm for studying other cancer types where altered RNA processing plays critical roles in development and progression of disease.

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