Ph.D. Yale University.
Research in our lab is directed towards understanding basic mechanisms of intracellular protein targeting. We use the yeastSaccharomyces cerevisiae which allows for a combined genetic and biochemical approach. Currently, we are pursuing three major areas of interest. One project focuses on understanding the molecular mechanism of quality control at the endoplasmic reticulum (ER): only properly folded proteins of the secretory pathway are allowed to advance to the cell surface while proteins which fail to fold properly are targeted for ER-associated degradation by cytosolic proteasomes. We are interested in understanding how a protein in the process of folding normally is distinguished from a misfolded one. A second major project is centered on protein sorting in distal secretory and endocytic pathways. Evidence is accumulating in support of a post-ER quality control mechanism that recognizes and targets defective proteins to the endosomal/vacuolar pathway for degradation. A third major project addresses the role of lipid rafts in maintaining protein stability upon arrival at the plasma membrane. We are studying the inter-relationships of protein phosphorylation, ubiquitination, and lipid raft association. In addition to playing a crucial role in cell compartmentation, these processes are all implicated in human health, as a wide range of diseases are associated with defects in protein trafficking in the secretory pathway, including cystic fibrosis and familial hypercholesterolaemia.
M. Liu, C.J. Huang, S.R. Polu, R. Schneiter and A. Chang (2012). "Regulation of sphingolipid synthesis via Orm1 and Orm2 in yeast." J. Cell Sci. Epub February 10.
Chunjuan Huang and Amy Chang (2011). "pH dependent cargo sorting from the Golgi." J. Biol. Chem. 286: 10058-10065. Epub Jan. 14, 2011
S. Han, M.A. Lone, R. Schneiter, A. Chang (2010). "Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control." Proc. Natl. Acad. Sci. Epub. March 8.
Y. Liu and A. Chang (2009). "A mutant plasma membrane protein is stabilized upon loss of Yvh1, a novel ribosome assembly factor." Genetics 181: 907-915.
Y. Liu and A. Chang. (2008). "Heat shock response relieves ER stress." EMBO J. 27: 1049-1059.
S. Han, Y. Liu, and A. Chang (2007). "Cytoplasmic Hsp70 promotes ubiquitination for ER-associated degradation of a misfolded mutant of the yeast plasma membrane ATPase, Pma1." J. Biol. Chem. 282: 26140-26149.