Investigating molecular mechanisms of membrane signaling complexes
Lipids are vital for both cellular structure and function. Disruptions to lipid metabolism can lead to diseases such as cancer and neurological disorders. Our laboratory wants to understand how lipid signaling is regulated, and why changes in lipid metabolism can lead to disease. We use structural biology, lipidomics, cancer biology and neuroscience to help drive the creation of mechanism-based therapeutics.
The research in our laboratory centers on the molecular mechanisms underlying the membrane protein complexes that are critical in the field of neuroscience and cancer biology. Specifically, we investigate the membrane lipid biology of proteins as well as the functionality of ion channels and receptors.
One interest of the lab is the biosynthesis and homeostasis of sphingolipids. Sphingolipids are one of the major membrane lipids in mammalian cells. They represent 10% to 20% of cellular lipids, and in certain specialized tissues, such as myelin sheaths, they can account for ~25% of the lipids. Sphingolipids are not only abundant structural components of membranes, but also function as signaling molecules and mediate a wide spectrum of cellular functions, including cell growth, adhesion, migration, and death. Defects in sphingolipid metabolism are often associated with cancers and neurodegenerative diseases. Sphingolipid production in cells is a highly regulated process. The sphingolipid biosynthetic pathway begins in the endoplasmic reticulum, where membrane enzyme complexes catalyze the first step of the process. Using cryo-EM, we aim to develop an atomic-scale understanding on how these enzymes are activated and regulated, as well as how their activities control sphingolipid homeostasis.
Although our research is currently grounded in science at the molecular level, we are developing exciting projects focused on membrane biology at the cellular level.
Dr. Chia-Hsueh Lee received his PhD from Oregon Health and Science University in 2015 and went on to complete his postdoc training with Dr. Roderick MacKinnon, making key discoveries elucidating the gating mechanisms of neuronal ion channels. In his faculty position in the Department of Structural Biology at St. Jude, Dr. Lee has taken on new challenges, building a growing research program focused on lipid metabolism and signaling. Dr. Lee is dedicated to creating a laboratory environment that embraces unique perspectives and diverse backgrounds, to ultimately drive innovative discovery.
A vibrant and dedicated team of protein structure enthusiasts.