Key words: ER and Golgi stress; Unfolded Protein Response (UPR); glucocorticoid signaling; gene knockout mice; animal stress; metabolism
During the course of our study of gene regulatary events in virus-host cell interactions, we have identified three new cellular proteins, Luman/CREB3, Zhangfei/CREBZF, and Luman-recruiting factor LRF (or CREBRF). We and others have since produced strong evidence suggesting that these proteins play key roles in cellular stress responses, specifically the Unfolded Protein Response (UPR) triggered primarily by disruption of homeostasis in the endoplasmic reticulum and the Golgi. The UPR has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimer’s, diabetes, cancer and viral infection.
In recent years our research has expanded from molecular genetics and cell biology to animal physiology and neuroscience. We have established CREB3- and CREBRF-gene knockout mouse models, both of which showed strikingly similar phenotype – lean and blunted stress response. We have since discovered that CREB3 and CREBRF are regulators of the glucocorticoid signaling and key modulators of lipid metabolism. Our ongoing research falls into the following themes –
1) How CREB3 and CREBRF mediate stress signaling, what their upstream and downstream targets are, and how this is related to cellular processes and animal diseases, such as metabolic disorders such as obesity/diabetes and animal stress-related disorders including animal welfare.
2) What are the genetic variations responsible for the differences among individuals in the response to stresses or susceptibility to metabolic disorders?