Raymond Moellering

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Chemical Platforms to Map & Manipulate Transcription Factor Signaling in Disease

Modern -omic technologies are providing associations between genetic variation and human disease at an incredible rate, however our ability to translate these findings into molecular probes and therapies is lagging behind. At the heart of this disconnect are challenges in two areas: 1) The ability to discover and map the relevant molecular networks that underly disease signals as they exist in cells, tissues and patients; 2) Difficulty developing molecules capable of targeting certain types of biomolecular interactions, with protein-protein and protein-DNA interactions resting at the center of this gap. Transcription factors (TFs), which regulate gene expression through sequence-specific recruitment to DNA, represent a large class of therapeutic targets that have remained largely ‘undruggable’ due to the challenges above. In this talk, I will discuss opportunities for new technologies to map and manipulate transcription factor form and function within the context of oncogenic signaling. In particular, I will focus on our development of a new class of hyperstable synthetic biologics that directly target oncogenic TFs.