Publications by authors named "J L Barrow"
Background: The activation of brown adipose tissue (BAT) is associated with improved metabolic health in humans. We previously identified the mitochondrial protein 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) as a novel regulatory factor that integrates with lipid metabolism and is critical to sustain the long-term activation of BAT, but the precise mechanism and function of Nipsnap1 is unknown.
Objectives: Define how the regulatory factor Nipsnap1 integrates with lipid metabolism.
The voltage-gated sodium channel Na1.8 (SCN10A) has strong genetic and pharmacological validation as a potential target for treating acute and chronic pain. While several different chemotypes have been advanced as selective inhibitors, a quinoxaline carboxamide core structure was identified as a particularly attractive core structure due to very high sodium channel subtype selectivity.
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- Ribosome biosynthesis is targeted as a vulnerability in cancer by inhibiting RNA polymerase I (Pol I) transcription, leading to the identification of specific Pol I inhibitors.
- Research showed that frameshift mutations in microsatellite unstable cancers increase sensitivity to these Pol I inhibitors, as RPL22 interacts with 28S rRNA and regulates RNA splicing.
- RPL22 deficiency triggers a complex response, promoting splicing changes and activating a tumor suppressive pathway through the inhibition of rRNA synthesis, revealing a key connection between ribosomal activity and mRNA splicing processes.
Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets.
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