Dr. Lin Liu joins the Department of Medicine

Dr. Lin Liu joined the Department of Medicine in the Division of Hematology as an Instructor in March, 2018.

During the course of Dr. Liu’s research training, he has maintained an interest in cell function, including exocytosis and endocytosis, protein or vesicle transport, signal pathway and related disease. The Golgi enzyme UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) mediates the first step in the addition of the mannose 6-phosphate targeting signal which serves to direct newly synthesized lysosomal enzymes to lysosomes. Dr. Liu is working on the role of the various domains of GlcNAc-1-phosphotransferase in selecting lysosomal enzymes as substrates over non-lysosomal glycoproteins. During the course of this work, he developed a form of GlcNAc-1-phosphotransferase (S1-S3) with enhanced ability to phosphorylate lysosomal enzymes. He is evaluating whether this property can be used to generate highly phosphorylated lysosomal enzymes that function better in enzyme replacement therapy which is the standard of care for a number of the lysosomal storage diseases. In addition, he is also working on the mechanism of glycosyltransferases Golgi localization. The glycosyltransferases of the mammalian Golgi complex must recycle between the stacked cisternae of that organelle to maintain their proper steady state localization.  This trafficking is mediated by COPI-coated vesicles, but how the glycosyltransferases are incorporated into these transport vesicles is not clear.  During the study of patient mutations in the N-terminal tail of GlcNAc-1-phosphotransferase, he and his team have found the N-terminal cytoplasmic tails of a number of cis Golgi glycosyltransferases which share a f-(K/R)-X-L-X-(K/R) sequence bind directly to the d and z subunits of COPI.