Targeted protein degradation is a new therapeutic modality based on drugs that destabilize
proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are …

The development of effective pharmacological inhibitors of multidomain scaffold proteins,
notably transcription factors, is a particularly challenging problem. In part, this is because many …

Traditional approaches in the development of small-molecule drugs typically aim to inhibit the
biochemical activity of functional protein domains. In contrast, targeted protein degradation …

Dissection of complex biological systems requires target-specific control of the function or
abundance of proteins. Genetic perturbations are limited by off-target effects, multicomponent …

Proteolysis-targeting chimeras (PROTACs) that degrade disease-causing proteins by
hijacking the endogenous ubiquitin-proteasome system have emerged as an exciting and …

Multi-dimensional omics profiling continues to illuminate the complexity of cellular processes.
Because of difficult mechanistic interpretation of phenotypes induced by slow perturbation, …

Little is known about the regulation of nonapoptotic cell death. Using massive insertional
mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-…

Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a
promising target for cancer therapy, particularly for cancers driven by transcriptional …

Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting
event in human gene control. A small number of regulatory factors influence …

Heterochromatin is required to restrict aberrant expression of retrotransposons, but it
remains poorly defined due to the underlying repeat-rich sequences. We dissected Suv39h-…