Membrane proteins can fail in many ways: they can misfold, misassemble, carry destabilizing mutations, expose normally hidden features, or become toxic when produced in the wrong context. Our lab studies how cells detect these defective membrane proteins and decide whether to repair, tolerate, or degrade them. This is a fundamental problem in cell biology, but it is also directly relevant to disease, since many mutations harm membrane proteins not by destroying their active sites, but by disrupting their folding, assembly, trafficking, or causing their premature degradation.
We are especially interested in how quality-control factors recognize problems within the membrane itself. What features mark a membrane protein as defective? How are these features sensed by chaperones and proteases? And why do some mutations push a protein across the line from functional to unstable or toxic? To answer these questions, we combine biochemistry, genetics, genetic screening, flow cytometry, proteomics, and quantitative stability assays in living cells.
