Our current focuses:
1. The function and regulation of noncanonical NF-kB signaling
NF-kB family of transcription factors has a pivotal role in regulating immune response, inflammation, and cell growth/survival, and deregulated NF-kB activation is linked to immunological disorders, including autoimmunity and chronic inflammation, as well as various cancers. NF-kB activation involves two major pathways: the canonical and noncanonical pathways. Despite the extensive studies of the canonical NF-kB pathway, much remains to be investigated regarding the regulation and functions of the noncanonical pathway. Unlike the canonical NF-kB pathway, which responds to diverse stimuli, the noncanonical NF-kB pathway selectively responds to a small subset of TNF receptor (TNFR) family members, including CD40, BAFF, and lymphotoxin-beta receptor (LTbR). Consistently, the function of noncanonical NF-kB pathway is more selective than that of the canonical pathway. Among the well-characterized functions of the alternative NF-kB pathway are secondary lymphoid organogenesis, thymic epithelial cell differentiation, B-cell survival and function, and bone metabolism5-8. However, it is important to note that our understanding of the noncaonical NF-kB functions is still incomplete.
Our lab will focus on the following major topics:
1. The crucial role of noncaonical NF-kB in unique type of tumor generation.
2. Identify the noncanonical specific target genes.
3. The mechanism of noncanonical NF-kB inducing gene regulation.
4. The noncanonical NF-kB inhibitor scanning.
2. The function of protein ubiquitination and phophorylation in autoimmune diseases
Ubiquitination and phophorylation have been reported that involved in multiple signaling transuding and disease process. Based on our previous experience, our lab will focus on the function and regulation of these protein modifications in autoimmune diseases. By comparing the different stimulated immune cell types, we plan to scan the cruicial E3 ubiquitin ligases and kinases. After that, we will generate the conditional KO mice to confirm its function in autoimmune disease process. By these findings, we will also try to find the specific inhibitors to prevent or therapy of multiple autoimmune diseases.