Proteostasis maintenance of membrane proteins in health and disease

• We welcome graduate students to join the laboratory for rotations and thesis work.

My laboratory aims to understand protein homeostasis (proteostasis) of ion channels. They are major drug targets; loss of their proteostasis and thus function leads to numerous diseases, including neurological, neurodegenerative, and cardiovascular diseases. To function, ion channel proteins must fold into their native structures and assemble properly in the endoplasmic reticulum (ER) for subsequent trafficking to the plasma membrane in a fully functional state. Variations in a given protein could lead to protein misfolding and excessive degradation through the ER-associated degradation (ERAD) pathway or autophagy, and thus a significantly lowered concentration of proteins in cell membranes and loss of function.

Currently, in my laboratory, we focus on studying neurotransmitter receptors, including gamma-aminobutyric acid type A (GABA_A) receptors, the primary inhibitory ion channels, and N-methyl-D-aspartate (NMDA) receptors, the major excitatory ion channels in the human brain. They mediate the inhibition-excitation balance in the mammalian central nervous system. Their dysfunction leads to epilepsies, autism, and other neurodevelopment diseases.

We explore how molecular chaperones, folding enzymes, degradation factors, and trafficking factors, coordinate to facilitate membrane protein folding, assembly, degradation, and trafficking.

We also use small molecules, incluing proteostasis regulators and pharmacological chaperones, to correct misfolded membrane proteins, as a therapeutic strategy to treat corresponding diseases.