Molecular Mechanisms of Membrane Transport

Selective transport of ions, drugs, and folded proteins across cell membranes, mediated by membrane transport proteins, is a fundamental biological process. Dysfunction of these membrane proteins leads to a wide range of diseases, including neurodegeneration, asthma, hypertension, cancer, diabetes, heart failure, and chronic pain. The Yuan lab is interested in structure and function of membrane transport proteins that play central roles in physiology and disease. Our long-term goal is to advance our understanding of structure and function of these essential membrane proteins at the atomic level and establish new foundations for rational therapies. Towards this end, we strive to develop new approaches and tools to investigate the molecular mechanisms of these challenging membrane proteins. How do channels and transporters recognize their specific substrates? How do channels open and close their pores in response to environmental cues and cellular stimuli, including chemicals, temperature, membrane voltage and mechanical force? To answer these fundamental questions, we use multidisciplinary approaches, including electrophysiology, biochemical and biophysical assays, and structural techniques including X-ray crystallography and cryo-electron microscopy. We are excited to provide an integrative understanding of structure and function of important membrane proteins and to establish solid foundations for mechanism-based drug design. Over the years, our lab has advanced understanding of structure and mechanism of a number of membrane proteins, including transient receptor potential (TRP) channels, copper transporters, proton-activated chloride channels, pannexin channels, and mechanosensitive channels. Our lab has recently relocated to Sinai. We look forward to our new chapter at Sinai and welcome motivated young scientists to join our team to make important discoveries.

Research directions:

• Structural Mechanism for Gating of Mechanosensitive Channels

• Molecular Mechanisms of Copper Transport

• Structure and Mechanism of TRP Ion Channels

• Antibiotic-sparing Strategies Targeting Outer Membrane Ushers in Gram-negative Bacterial Pathogens

• Mechanism and Inhibition of Membrane Transport in Malaria Parasites