P. Gopal

UPF1 localises to mitochondria and is linked to mitochondrial gene expression and function in Drosophila

This study shows UPF1 localizes to mitochondria in Drosophila and affects mitochondrial gene expression and function independently of its role in NMD.

Liver cancer initiation is dependent on metabolic zonation but decoupled from premalignant clonal expansion

This study shows that liver cancer initiation depends on metabolic zonation but is not linked to premalignant clonal expansion.

Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease

The paper identifies adaptive pathways in metabolic liver disease by selecting somatically mutated clones in mice and humans, finding mutations that ameliorate lipotoxicity and promote clonal expansion.

Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death

This study shows that targeted degradation of PCNA via biodegraders leads to more effective anti-proliferative effects and programmed cell death compared to stoichiometric inhibition.

Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling

This paper identifies macrocyclic peptides that inhibit KRAS signaling by binding to its hydrophobic pocket, showing on-target activity and improved proteolytic stability.

Ablating Ku70 phosphorylation results in defective DNA damage repair and spontaneous induction of hepatocellular carcinoma

This study shows that ablation of Ku70 phosphorylation leads to defective DNA repair and spontaneous hepatocellular carcinoma in mice.

STUB1 is an intracellular checkpoint for interferon gamma sensing

This study identifies STUB1 as a barrier to interferon gamma sensing, showing it dampens IFNγ response through reduced IFNGR1 surface abundance, but in vivo STUB1 inactivation did not improve ICB outcomes in mouse models.

bioPROTACs establish RAS as a degradable target and provide novel RAS biology insights

The paper demonstrates that RAS proteins can be degraded using bioPROTACs and provides insights into the functional consequences of RAS degradation and mutant susceptibility.

Pyrazinamide triggers degradation of its target aspartate decarboxylase

This paper shows that pyrazinamide's active form, POA, triggers degradation of its target enzyme PanD via the ClpC1-ClpP protease, rather than inhibiting it directly.

Phase variation in Mycobacterium tuberculosis glpK produces transiently heritable drug tolerance

This paper identifies a novel mechanism of drug tolerance in M. tuberculosis through phase variation in the glpK gene, showing reversible frameshift mutations that contribute to treatment failure and relapse.