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Research Summary
Research in our laboratory focuses on the mechanisms governing the pathogenesis of cardiometabolic and liver diseases. Particularly, we are interested in how innate immune network modulates these diseases with an emphasis on cardiac remodeling, vascular injury, ischemia/reperfusion injury, obesity,insulin resistance, and hepatic steatosis. Our goal is to identify the fundamental basis that may be employed by these diseases and reveal molecular pathways for therapy.
We are very interested in how innate immune signaling mediators such as interferon regulatory factors (IRFs), toll-like receptor-associated factors (TRAFs), CARDs, DKKs, A20, ABINs, Mindin, Tollip, RECS1, SIKE etc. may response to the stresses causing various pathological conditions relevant to cardiometabolic diseases. We have found that IRFs may play distinct roles in cardiac hypertrophy, hepatic ischemia/reperfusion (I/R) injury, hepatic steatosis, and insulin resistance. Interestingly, these factors may not necessarily function through modulating immune response. They rewire signaling pathways through extensive crosstalk and their functions (positive or negative) in these pathologies are not always consistent to their roles in the innate immune response. Intriguingly, even though two different cardiometabolic conditions worsen each other, a certain IRF may exhibit opposite functions in these two pathologies. Such unique features have been also observed in TRAFs and other molecules and these findings have been confirmed in human patient samples and large animal models. For instance, introducing SIKE into the monkeys protects then from cardiac hypertrophy induced by blood pressure overload, emphasizing a clinical and therapeutic significance of these results. These findings have established a novel conception that innate immune network may function in the pathogenesis of cardiometabolic diseases in an immune-independent manner.

These researches significantly boost our insight into the pathogenesis of cardiometabolic diseases. Our knowledge of innate immune network in these diseases may also be applicable in other diseases such as acute lung injury. From a clinical perspective, a thorough understanding of the role and mechanism of innate immune network in these diseases will significantly promote the related translational medicine research towards the development of novel therapy for these diseases.

Summary of Innate Immune network in Cardiometabolic Disease