William G. Kaelin

Cullin-5 RING E3 ligase limits CD8⁺ T-cell persistence and effector responses during chronic antigen stimulation

Abstract T-cell exhaustion limits durable antitumor responses and remains a barrier to adoptive cell therapies (ACT) in solid tumors. To identify regulators of T-cell persistence, we performed genome-wide CRISPR knockout screens in primary human CD8⁺ T cells expressing an NY-ESO-...

Positive selection screen identifies natural product β-catenin inactivators

Many genetically validated targets in cancer, including the transcription factor β-catenin (β-cat), have historically been viewed as undruggable. Cell-based phenotypic screening of chemical compounds can reveal unanticipated biological and pharmacological principles. Natural prod...