David J. Beech

Tissue-specific endothelial cell heterogeneity in human type 2 diabetes

The paper examines transcriptomic heterogeneity of microvascular endothelial cells in subcutaneous adipose tissue and skeletal muscle in type 2 diabetes, finding stress in SAT but not SkM.

Endothelial Piezo1 regulates muscle AKT abundance and mechanically induced muscle hypertrophy

This study shows endothelial Piezo1 promotes mechanical overload-induced muscle hypertrophy by regulating AKT abundance, but not muscle regeneration.

(-)-Englerin A binds a conserved lipid site of TRPC5 and exposes a Met-aromatic motif in channel activation

This study presents cryo-EM structures of TRPC5 bound to (-)-englerin A, revealing its binding site and mechanism of activation.

Two-pore channel protein 2-mediated calcium release promotes angiopoietin 2 secretion by regulating Rab46-dependent Weibel-Palade body trafficking

The paper shows that TPC2-mediated Ca2+ release regulates Rab46-dependent Weibel-Palade body trafficking, promoting Ang2 secretion in endothelial cells.

Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells

This paper identifies a small molecule that reduces IR:IGF-1R hybrid formation in human endothelial cells, increasing Akt phosphorylation and altering PI3-kinase signaling.

Small-molecule functional rescue of PIEZO1 channel variants associated with generalised lymphatic dysplasia

The paper identifies and characterizes novel PIEZO1 variants associated with GLD, showing they impair mechanosensitivity and demonstrating small-molecule rescue of channel function.

Cryo-EM structures of human TRPC5 reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site.

The paper reports the cryo-EM structure of human TRPC5 bound to the xanthine inhibitor Pico145, revealing its interaction with a conserved lipid binding site and elucidating the mechanism of TRPC1/4/5 modulation.