The Wang lab studies Neuroinflammation and Neurodegenerative diseases. The lab has a focus on several topics:
- Diseases of brain autoinflammatory caused by genetic mutations.
- Cellular RNA procession, modification and detection.
- RNA regulated innate immune signaling pathways.
- IFN signaling pathway and diseases.
- Disease animal models of neuroinflammation and degeneration.
The Wang Lab has been working on the function and molecular mechanisms of RNA processes, particularly the RNA editing process. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that binds to and changes the sequence information of RNA molecules. We have demonstrated that ADAR1 is an essential enzyme for animal survival and embryonic development. In ADAR1 knockout mice, embryo die around day 11-12. Employing conditional and inducible knockout models, we also found that adult cells, including adult stem cells, require ADAR1 for their differentiation and normal functions. ADAR1 is dispensable for the homeostasis of organs including the liver, pancreas, and intestines, as well as that of T and B lymphocytes and the skin. For example, in a liver-specific knockout animal model, deletion of ADAR1 caused profound hepatocyte death and persistent liver regeneration that led to severe liver function damage.
There is evidence that ADAR1 is involved in interferon (IFN) signaling pathways. In ADAR1 knockout animals, IFN levels and its regulated genes are upregulated. IFNs play critical roles in pathogen infections and also in inflammation responses. It conceivable that cells change their RNA content biologically or by invading pathogens that need ADAR1 to copy with. Inappropriate RNA processes owill activate the IFN pathway cascade that could lead to severe tissue damage. We currently focus our interests in the function of ADAR1 in the surgical pathological context. Hopefully, our research will contribute to a better understanding of the molecular mechanisms of inflammation development in surgical infection and trauma.