The ongoing studies in my laboratory focus on innate immunity and the damage-associated molecular pattern (DAMP) danger response, specifically, the role of DAMPs and pattern recognition receptors in injury-induced inflammation and tumorigenesis of primary and metastatic liver cancer. My seminal findings implicate high mobility group box protein 1 (HMGB1) as an early mediator following acute, local organ injury, as in liver ischemia and reperfusion (I/R). I have developed my research program based on the hypothesis that ischemic parenchymal cells mobilize and release nuclear HMGB1 as a way to notify adjacent immune cells of impending tissue injury. This, in turn leads to activation of an inflammatory response that when excessive, contributes to further tissue damage. These inflammatory responses can also alter the local microenvironment leading to cancer progression via tumor cell survival, expansion, and metastases. My laboratory has recently demonstrated the novel finding that neutrophils can form neutrophil extracellular traps (NETs) in response to surgical stress to the liver (i.e. I/R) and that targeting NETs ameliorates the hepatic as well as systemic inflammation in mice. Our latest exciting findings demonstrate that increased NET formation following surgical stress of the liver also results in the acceleration of both the development and progression of metastatic disease. Because alterations in autophagy underlie mechanisms of a number of common hepatic diseases, I am also interested in understanding the roles that autophagy can play in normal hepatic physiology as well as in pathophysiological conditions, including hepatocellular carcinoma and I/R liver injury. The combination of these studies will provide a more comprehensive understanding of how inflammatory pathways promote organ injury after ischemic insults and should prove useful in the design of novel therapies to minimize tissue damage and improve liver function in a variety of disease states.
- Principal Investigator: Allan Tsung, MD
- Dirk Van der Windt
- Eva Lin
- Hai Huang
- Hamza Obaid Yazdani
- Hongji Zhang
- Jinghua Ren
- Patrick Bou-Samra
- Xinghua Liao
Biomedical Science Tower, W1504, W1510
Publications from the Tsung Lab can be viewed through PubMed.