The secretory pathway is responsible for the processing and trafficking of a wide variety of protein cargoes including hormones, enzymes, receptors, ion channels and transporters. The balance between synthesis, folding, transport, degradation and secretion of these proteins in the secretory pathway is vital for cell and organism survival. The disruption of this homeostasis can lead to numerous human diseases such as cystic fibrosis, Alzheimer’s disease, diabetes and pancreatitis. In spite of the importance of the secretory pathway and the extensive research in past decades, there are many questions remained unsolved including the detailed molecular mechanisms for cargo sorting and maintenance of the identities of different membrane compartments, and most importantly the regulation of the molecular machinery in the secretory pathway under different physiological and pathological conditions. Our current incomplete understanding of these fundamental mechanisms precludes the efficient treatment of the above human diseases. The long term research goal of my lab is, using systems physiology approaches and specialized secretory tissues as models, to understand the molecular machinery of the secretory pathway governing the intracellular protein homeostasis and trafficking, and more importantly the regulation of the machinery under different metabolic, physiological and pathological conditions. My research has been focused on cellular physiology and functional proteomics studies of protein homeostasis and membrane trafficking in mammalian secretory pathway such as the endoplasmic reticulum homeostasis in normal and diseased states, molecular architecture and regulated exocytosis of secretory granules and cell cycle regulated Golgi biogenesis. The systems physiology approaches used in our research are the combination of the quantitative mass spectrometry technology, cellular and integrative physiology, biochemistry and bioinformatics approaches.