Paul A. Clemons

TL;DR: The first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules is created, and it is demonstrated that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs.

TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.

TL;DR: The expanded CMap is reported, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that is shown to be highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts.

TL;DR: Vulnerability to ferroptic cell death induced by inhibition of a lipid peroxidase pathway as a feature of therapy-resistant cancer cells across diverse mesenchymal cell-state contexts is identified.

TL;DR: This work focuses on target-identification and mechanism-of-action studies, which allow small-molecule action to be tested in a more disease-relevant setting at the outset, but require follow-up studies to determine the precise protein target or targets responsible for the observed phenotype.