Bruno N. Melillo

This study identifies a small molecule targeting PSME4, which stabilizes STAT1 and reprograms tumor inflammation, suppressing tumor growth by altering cytokine signaling.

ESCAPE identifies covalent ligand-protein interactions by using prime editing to disrupt cysteine residues and assesses their impact on cellular phenotypes.

The paper compares acrylamide and butynamide stereoprobes to identify covalent inhibitors of the actin maturation protease ACTMAP in human cancer cells.

The paper develops a Minimum Inoculum for Resistance (MIR) assay to evaluate anti-Toxoplasma gondii compounds, showing that inhibitors of phenylalanine tRNA synthetase require higher parasite inocula to induce resistance compared to DNA synthesis inhibitors.

The paper identifies ortholog-restricted cysteines in Z. tritici that are targeted by stereoprobes, revealing potential fungicidal targets for combating wheat pathogens.

This study uses high-throughput chemistry to discover chemical inducers of proximity by modifying pre-existing ligands and screening for degrader activity.

The paper identifies host proteins regulating Mycobacterium tuberculosis replication in macrophages using cysteine reactivity profiling and genetic perturbation.

This paper reports covalent ligands targeting the RNA-binding protein NONO, showing they stabilize mRNA interactions, remodel transcriptomes, and suppress cancer cell growth with high specificity.

The paper develops covalent ligands that specifically target a complexoform of TRMT112, revealing partner-specific functional effects through allosteric activation of METTL5.

The paper identifies inhibitors of the GRPEL1-HSPA9 chaperone complex using tryptoline stereoprobes and shows they target non-orthosteric sites.

The paper identifies LPCAT3 as a cold-regulated enzyme that generates AA-PE in BAT mitochondria, enhancing ETC efficiency and thermogenesis.

The paper uses stereoprobes to identify covalent ligands for proteins, revealing TLCD1 as a lipid acyltransferase inhibited by OTP stereoprobes.

This study develops chemical probes to target splicing factors in T cells, showing state-dependent loss of ITK via SF3B1 and demonstrating covalent ligandability of splicing regulators.

The paper introduces photo-stereoprobes for expanding the ligandable proteome and demonstrates their use in discovering bioactive small molecules.

This study identifies covalent small molecules that bind FOXA1, altering its chromatin remodeling activity in prostate cancer cells.

The paper uses covalent probes and paralog hopping to identify ligandable pockets in proteins lacking cysteines, demonstrating a method to expand the ligandable proteome.

This paper describes new bicyclic pyrrolidine inhibitors of Toxoplasma gondii PheRS with improved potency, selectivity, and brain exposure compared to previous azetidine-based inhibitors.

The paper uses base editing to assess the functional impact of cysteine mutations in cancer dependency genes, identifying essential and ligandable cysteines for drug development.