R. K. Semple

Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

The paper investigates an activating PIK3R1 variant linked to immunodeficiency and finds it acts as a dominant negative, reducing p110 signaling and explaining overlapping phenotypes.

Female Alms1-deficient mice develop echocardiographic features of adult but not infantile Alström Syndrome cardiomyopathy

Mesenchymal-specific Alms1 knockout in mice recapitulates key metabolic features of Alström Syndrome

This study shows that deleting Alms1 in mesenchymal cells in mice causes metabolic issues similar to Alström Syndrome, including insulin resistance and fatty liver.

Loss of Mfn1 but not Mfn2 enhances adipogenesis

The paper shows that loss of Mfn1 promotes adipogenesis in cultured cells, while loss of Mfn2 does not, indicating distinct roles for Mfn1 and Mfn2 in adipocyte differentiation.

A mouse model of human mitofusin 2-related lipodystrophy exhibits adipose-specific mitochondrial stress and reduced leptin secretion

This study uses a mouse model to show that a MFN2 mutation causes adipose-specific mitochondrial stress and reduced leptin secretion, linking mitochondrial dysfunction to metabolic disease.

Transcriptomically-inferred PI3K activity and stemness show a counterintuitive correlation with PIK3CA genotype in breast cancer

The paper finds a biphasic relationship between PIK3CA genotype and transcriptionally inferred PI3K activity and stemness in breast cancer, with mutant allele dosage affecting these traits differently.

Evaluation of anti insulin receptor antibodies as potential novel therapies for human insulin receptoropathy

Anti-insulin receptor monoclonal antibodies activate specific mutated human insulin receptors, suggesting potential as novel therapies for insulin receptoropathy.