Lipidomic profiling of mouse brain and human neuron cultures reveals a role for in mTOR-dependent neuronal migration.

Mutations in lipid regulator genes are a frequent cause of autism spectrum disorder, including those regulating phosphatidylinositol (PI) and phosphoinositide 3-kinase signaling. encodes a key acyltransferase in PI synthesis and is mutated in an autism-related condition with neurodevelopmental delay and epilepsy. Using liquid chromatography-tandem mass spectrometry, we analyzed the PI-associated glycerolipidome in mice and humans during neurodevelopment and found dynamic regulation at times corresponding to neural apoptosis in the brains of knockout mice.

SF3B1 thermostability as an assay for splicing inhibitor interactions.

The spliceosome protein, SF3B1 associates with U2 snRNP during early spliceosome assembly for pre-mRNA splicing. Frequent somatic mutations in SF3B1 observed in cancer necessitates characterization of its role in identifying the branchpoint adenosine of introns. Remarkably, SF3B1 is the target of three distinct natural product drugs, each identified by their potent anti-tumor properties.

Exploiting the DCAF16-SPIN4 interaction to identify DCAF16 ligands for PROTAC development.

Traditional small molecule drugs often target protein activity directly, but challenges arise when proteins lack suitable functional sites. An alternative approach is targeted protein degradation (TPD), which directs proteins to cellular machinery for proteolytic degradation. Recent studies have identified additional E3 ligases suitable for TPD, expanding the potential of this approach.

Aspirin modulates generation of procoagulant phospholipids in cardiovascular disease, by regulating LPCAT3.

Enzymatically oxygenated phospholipids (eoxPL) from lipoxygenases (LOX) or cyclooxygenase (COX) are prothrombotic. Their generation in arterial disease, and their modulation by cardiovascular therapies is unknown. Furthermore, the Lands cycle acyl-transferases that catalyze their formation are unidentified.

Chemical probes for the identification of the molecular targets of honokiol.

Honokiol is a natural product with an interesting array of biological effects, including significant anti-tumor properties. However, full exploration of its therapeutic potential is hampered by its modest pharmacokinetic profile and by the lack of synthetic methods that allow to obtain specifically designed derivatives with improved properties. In addition, the specific molecular targets of honokiol remain poorly understood, a fact that limits the search of alternative hits for subsequent optimization programs.