Michael Erb

Proximity pharmacology enables biochemical events to be rewired with temporal precision, offering privileged insights into cell biology that are difficult to access with traditional genetic approaches or conventional small-molecule drugs. To uncover chemical inducers of proximity that rewire chromatin-regulated processes, we combine innovative discovery chemistry approaches (e.g. SuFEx-based high-throughput chemical synthesis) with bespoke cell-based screening assays, forward genetic screens, and integrative transcriptional genomics. These efforts have enabled us to: (i) broaden the scope of ligandable proteins to “undruggable” transcription factors, (ii) harness previously unrecognized effectors for targeted protein degradation, and (iii) target homologous recombination (HR)-deficient tumors by recruiting heterologous proteins to sites of DNA damage. Collectively, these studies provide a blueprint for expanding proximity pharmacology into previously inaccessible biological spaces.