Graham Dickson and Hugh MacLeod

Phosphorylation-driven Targeted Protein Degradation of Oncogenic β-catenin

This study identifies induced-proximity drugs that target β-catenin in colorectal cancer by recruiting Casein kinase I, leading to its degradation and inhibiting tumor growth.

SRRM1 coordinates an alternative splicing program that promotes expression of oncogenic protein isoforms.

This study identifies SRRM1 as a splicing regulator that promotes oncogenic NUMB isoforms and other cancer-related splicing events, leading to increased tumorigenic properties in multiple cancer cell lines.

Targeting synthetic lethality between non-homologous end joining and radiation in very high-risk SHH medulloblastoma

This study identifies DNA-PK as a synthetic lethal target in TP53-deficient SHH medulloblastoma, showing that inhibiting DNA-PK enhances radiosensitivity and improves survival in preclinical models.

Identification of Injury-Response State Determinants in Glioblastoma Stem Cells

This study identifies EP300 as a regulator of the Injury-Response state in Glioblastoma Stem Cells through a CRISPR-Cas9 screen, showing its role in maintaining IR state features and tumor aggressiveness.

PRMT5 is required for full-length HTT expression by repressing multiple proximal intronic polyadenylation sites

This paper identifies PRMT5 as a regulator of HTT mRNA splicing and alternative polyadenylation, showing that its inhibition reduces full-length HTT protein levels by promoting premature termination and cleavage.

The CDK12 inhibitor SR-4835 functions as a molecular glue that promotes cyclin K degradation in melanoma

This study identifies SR-4835 as a CDK12 inhibitor that promotes cyclin K degradation via the proteasome by recruiting the CDK12-cyclin K complex to the CUL4-RBX1-DDB1 ubiquitin ligase complex.