Zhang Laboratory

Research in this laboratory is focused on stress signaling and the inflammatory response originated from the endoplasmic reticulum (ER) and/or mitochondria that modulate cell metabolism and disease pathogenesis. The ER is an organelle that is primarily recognized as a compartment for protein folding and assembly, a pool of intracellular calcium, and a site for lipid and sterol biosynthesis. Physiological states that increase protein-folding demand, or stimuli that disrupt protein folding reactions, create an imbalance between the protein-folding load and capacity of the ER. This can cause accumulation of unfolded or misfolded proteins in the ER lumen -a condition referred to “ER stress”. To ensure the fidelity of protein folding and to handle the accumulation of unfolded or misfolded proteins, the ER has evolved a group of signal transduction pathways collectively termed “Unfolded Protein Response (UPR)” to alter transcriptional and translational programs. It has been recognized that the UPR signaling is critical for the initiation and progression of a variety of human diseases, including metabolic disease, cancer, cardiovascular disease, and neurodegenerative disease. Research projects in this laboratory include: 1) regulation of hepatic energy metabolism by ER stress-induced transcriptional activators; 2) roles and mechanisms for the UPR Transducer IRE1a in Autoimmune Diseases; 3) airborne particulate matter(PM2.5)-induced inflammatory stress response and its effect on non-alcoholic fatty liver disease (NAFLD) and type-2 diabetes; 4) roles of ER lipid-raft proteins in breast cancer malignancy maintenance and therapy resistance; and 5) remodeling macrophage inflammation and foam cell formation by the unfolded protein response;