Welcome to the Pleiner lab

The protein homeostasis (proteostasis) network controls cellular protein biosynthesis, folding and degradation to prevent toxic protein misfolding or aggregation. Perturbation of proteostasis results in the activation of cellular stress pathways, which exert their control on the transcriptional and translational level to adjust the cellular biosynthetic, folding and degradative capacity to restore proteome balance. Dysregulation of proteostasis is central to many diseases including cancer and neurodegeneration, and is also a hallmark of ageing. A mechanistic understanding of proteostasis as well as its manipulation for therapeutic benefit is therefore a central goal of modern molecular biology

Our lab is particularly interested in membrane protein homeostasis: How does the cell make and quality control multi-pass membrane proteins like transporters, receptors and ion channels that are essential for cellular physiology? We combine mechanistic cell biology, (structural) biochemistry and protein engineering to dissect the pathways and molecular machines that mature the ~5,000 human membrane proteins to a fully functional state.

We are developing alpaca-derived nanobodies as tools to acutely perturb such dynamic intracellular pathways directly at the protein level and assess immediate functional consequences to the nascent (membrane) proteome. We will generate highly specific reagents to fine-tune the cellular stress responses that control cellular protein folding and degradation capacity. Such reagents will be powerful tools to either correct or increase the dysregulation of protein homeostasis in neurodegeneration/ ageing or cancer, respectively.

The Pleiner lab @ Stanford Medicine will open its doors in June 2023 in the Department of Molecular & Cellular Physiology (MCP) @ Stanford Medicine.

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