D. Barsyte-Lovejoy

A resource to enable chemical biology and drug discovery of WDR Proteins

The paper develops a resource for discovering ligands for WDR proteins using experimental and computational methods, leading to the identification of drug-like ligands for 9 out of 20 targets.

Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations

This study identifies epigenetic vulnerabilities in AML and MDS/MPN with EZH2 mutations, showing increased sensitivity to EZH2 and EED inhibitors and upregulation of cell death pathways.

Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex

The paper develops chemical tools and probes for the Gid4 subunit of the human CTLH E3 ligase complex, achieving sub-100 nM binding affinity for further study.

Recruitment of FBXO22 for Targeted Degradation of NSD2

This paper describes a targeted protein degradation strategy using UNC8732 to recruit FBXO22 for NSD2 degradation, leading to growth suppression and reversal of drug resistance in leukemia cells.

Probing the DCAF12 interactions with MAGEA3 and CCT5 C-terminal degrons

This study characterizes DCAF12 interactions with MAGEA3 and CCT5 degrons using biophysical assays and cryo-EM, revealing key residues for degron recognition and informing PROTAC design.

Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor

The paper investigates how a small-molecule inhibitor binds to and inactivates Cbl-b, revealing a structural mechanism that locks the protein in an inactive conformation.

Discovery and characterization of a chemical probe targeting the zinc-finger ubiquitin-binding domain of HDAC6

The paper identifies and characterizes a chemical probe, SGC-UBD253, that targets the HDAC6 UBD with selectivity, and a less active derivative as a negative control.

A combinatorial anticancer drug screen identifies off-target effects of epigenetic chemical probes

This study identifies epigenetic chemical probes that enhance TAK-243 cytotoxicity via off-target ABCG2 inhibition and develops a cell-based assay to measure ABCG2 inhibition.

Reference compounds for characterizing cellular injury in high-content cellular morphology assays

The paper profiles 218 cytotoxic and nuisance compounds in U-2 OS cells to create reference compounds for improving assay optimization and compound prioritization in cellular morphology assays.

PRMT5 regulates ATF4 transcript splicing and oxidative stress response

This study shows PRMT5 regulates ATF4 splicing and oxidative stress response in AML, with EVI1-high cells depending on PRMT5 for redox balance.

Regulation of skeletal muscle metabolism and contraction performance via teneurin-latrophilin action.

The paper identifies a novel teneurin/TCAP-LPHN system that regulates skeletal muscle contractility and fatigue through insulin-independent glucose importation and cytosolic Ca2+ signaling.

PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade

This study shows PRMT7 inhibition enhances anti-tumor immunity and improves response to immune checkpoint blockade in melanoma by modulating immune cell infiltration and PD-L1 expression.

Design, Synthesis and Evaluation of WD-repeat containing protein 5 (WDR5) degraders

This study designs, synthesizes, and evaluates two series of WDR5 degraders, showing that linker length and nature affect degradation efficacy.

Pharmacological targeting of a PWWP domain demonstrates cooperative control of NSD2 localization

The paper develops a chemical probe, UNC6934, that targets the PWWP1 domain of NSD2, revealing cooperative control of NSD2 localization through chromatin reader domains.

A First-in-class, Highly Selective and Cell-active AllostericInhibitor of Protein Arginine Methyltransferase 6 (PRMT6)

This paper reports the discovery of a first-in-class, highly selective allosteric inhibitor of PRMT6, SGC6870, with potent activity and selectivity in vitro and in cells.

Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2

This study identifies small-molecule antagonists of the NSD2 PWWP domain that block its interaction with H3K36me2, providing a tool for further investigation of NSD2's role in disease.

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response

This study identifies a PRMT7 inhibitor and shows its effect on arginine methylation of stress proteins, linking PRMT7 to cellular stress response.