I. Unfolded Protein Response and Human Diseases
During the course of our study of gene regulation events in virus-host cell interaction, we have identified three new cellular proteins, Luman/CREB3, Zhangfei/CREBZF, and Luman-recruiting factor (LRF). These proteins play key roles in animal stress responses, specifically the Unfolded Protein Response (UPR) that is caused by stress in the endoplasmic reticulum. 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. We are currently using gene knockout mouse models, combined with molecular and cellular biology techniques to study -
- Stress signaling mediated by these proteins (their upstream and downstream targets), and how it is related to cellular processes or animal diseases (lipid metabolism/obesity, hypoxia/cancer, glucose metabolism/diabetes, and inflammation);
- The molecular mechanism of how these genes/proteins are regulated during the stress response (e.g., transcriptional regulation, protein translational modification and trafficking etc).
II. Molecular Mechanisms of Aging
Another new and exciting field that we have recently undertaken is to study of the mechanisms of aging using planarians (flat worms). The planarians are potentially a better model system than traditional fruitflies and C. elegans (round worms), both of which have undergone extensive gene loss during evolution and are largely post-mitotic in their adult life. We are working to establish planarians as a new aging model to test the hypothesis that longevity requires multiplex resistance to stress. We hope to identify genes or alleles that confer such multiplex stress resistance and/or promote longevity.
Keywords: cell signaling, animal stress response, unfolded protein response, gene-knockout mouse, virus-cell interaction, aging mechanism, planarians