The Mu laboratory aims to understand protein homeostasis (proteostasis) of membrane proteins. They are major drug targets; loss of their proteostasis leads to numerous diseases, including neurological, neurodegenerative, and cardiovascular diseases. To function, membrane proteins need to fold into their native structures and assemble properly in the endoplasmic reticulum (ER) for subsequent trafficking to the plasma membrane or their intended destinations in a fully functional state. Mutations in a given protein could lead to protein misfolding and excessive ER-associated degradation (ERAD), and thus a significantly lowered concentration of proteins in their functional locations and loss of function.
Currently, the Mu lab focuses on neurotransmitter-gated ion channels, including gamma-aminobutyric acid type A (GABAA) receptors and N-methyl D-aspartate (NMDA) receptors. They mediate the excitation inhibition balance in the mammalian central nervous systems. Their functional defect leads to epilepsy, autism, intellectual disability, and other neurodevelopmental diseases.
The Mu lab explores how molecular chaperones, folding enzymes, ERAD factors, and trafficking factors, coordinate to facilitate membrane protein folding, assembly, degradation and trafficking.
The Mu lab also uses small molecule proteostasis regulators to correct pathogenic membrane proteins with protein conformational deficiency, as a therapeutic strategy to treat corresponding diseases.