When
Abstract:
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 dynamic 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 large protein interfaces resting at the center of this gap. Transcription factors (TFs), which are proteins that 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 our development of a new class of fully synthetic transcription factor mimetics, which can directly inhibit TF-DNA binding with high affinity and specificity. These synthetic transcriptional repressors (STRs) mirror the modularity found in Nature and can thus be programmed to target entire families of TFs. To demonstrate this potential, I will discuss the application of this approach to target two notorious transcription factors: MYC and HIF1a. In both of these areas, the ability to access and chemically access these ‘synthetic biologic’ structures has enabled us to gain fundamental insights into oncogenic transcriptional regulation, as well as glimpse the future promise of directly modulating TF function in cells and animals.
PRESENTER
Dr. Raymond Moellering Associate Professor, Department of Chemistry, University of Chicago
Hosted by:
Dr. Michael Taylor