Assistant Professor, Biodesign Center for Applied Structural Discovery
Dr. Wei Liu joined the School of Molecular Sciences and Biodesign Institute at ASU in 2015. He came to ASU from the Scripps Research Institute and the Ohio State University, where he spent over a decade developing new tools for studying the structure and function of membrane proteins with a focus on GPCRs involved in cancer.
Dr. Liu earned a B.S. in pharmacology from Wuhan University in China in 2002 and a Ph.D. in biophysics from the Ohio State University in 2007 under the mentorship of Prof. Martin Caffrey, which ignited his passion for studying membrane proteins and developing lipidic cubic phase (LCP) technology. He then joined the lab of Prof. Raymond Stevens and Prof. Vadim Cherezov at the Scripps Research Institute where he played a critical role in solving the first high-resolution structure of human adenosine A2A receptor with a novel fusion protein (BRIL) at 1.8 angstrom resolution, by far the highest resolution of all human membrane protein structures and was highlighted by Science Magazine. The scientific insights and technical advances from this initial work were used by Dr. Liu and colleagues to solve the structures of 10 additional unique human GPCRs. These structures have enhanced our understanding of how GPCR folding has evolved to bind such a large and diverse pool of natural ligands.
More recently, Dr. Liu has applied his LCP crystallization methods for studying GPCRs using X-ray free electron lasers (XFEL), which does not require sample freezing, has the potential to minimize radiation damage (if any) during data collection due to the ultrashort (femtosecond) pulse duration, and only requires relatively small crystals making it much more accessible for many GPCRs recalcitrant to crystallization. Dr. Liu solved the first human membrane protein and GPCR structure using XFEL, the human serotonin 5-HT2B receptor. Assistant Professor Liu’s growing body of work now encompasses over 30 peer reviewed publications, including 16 in Nature, Science and Cell journals with over 4300 citations since 2010.
ASU Structural Biology of Cancer Laboratory
Assistant Professor Wei Liu’s laboratory uses lipidic cubic phase (LCP) technology to study proteins, the molecular building blocks of life, and examines their structure and function using high-powered X-ray lasers. His research will lead to insightful structural and mechanistic understandings of molecules that are instrumental in the progression of various devastating diseases, including cancer, and will stimulate designing novel, specific and effective drugs with fewer side effects.
Knowledge on the Structural Level Improve Human Health
The intricate orchestration of various activities within our bodies is enabled by tiny molecular machines called proteins. Proteins carry out most, if not all, biological processes critical for human survival, including physiological metabolism, tissue repair, and immune responses to invading pathogens. A specific protein family, called G-protein-coupled receptors (GPCRs), constitute the communication channels relaying messages from both within and outside the human body, including the perception of sight, smell, and taste. GPCRs gone awry can lead to developing a myriad devastating diseases such as cancer. Furthermore, cancer cells may also hijack GPCRs to evade surveillance by the immune system. Not surprisingly, GPCRs have become the most important drug targets on market.
Proteins structures are necessary to further our understanding of their dynamics, the physical and chemical processes they participate in, and the biological processes they regulate. Without detailed atomic structures, designing drugs that target a specific protein is just shooting in the dark. Recent advancements in state-of-the-art, high-powered X-ray laser technologies have the potential to provide unprecedented structural details on how drugs interact with their protein targets, and thus could significantly accelerate the discovery and development of effective therapies.
Assistant Professor Wei Liu is working with other members of the Biodesign Institute Center for Applied Structural Discovery and distinguished international collaborators in developing revolutionary technologies for taking snapshots and “molecular movies” of proteins in action, together with a series of drugs, to understand how they interact, which will lead to developing more effective therapeutics at a lower cost.