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Allan Tsung, MD



Liver Cancer Center, UPMC Montefiore Hospital, 3459 Fifth Avenue
Pittsburgh, PA 15213
Phone: (412) 692-2001

Roberta G. Simmons Associate Professor; Division of Hepatobiliary and Pancreatic Surgery

MD, SUNY Health Science Center at Brooklyn, Brooklyn, NY; BS, Cornell University, Ithaca, NY

Research Area(s):

Liver Inflammation and Innate Immunity

The ongoing studies in my laboratory focus on the role of endogenous damage-associated molecular pattern (DAMP) molecules and pattern recognition receptors in ischemia-induced inflammation of the liver during ischemia reperfusion (I/R) injury, sepsis, and cancer. We are currently investigating the mechanisms by which high mobility group box 1 (HMGB1), a nuclear DAMP protein, can act as a key alarm molecule when released extracellularly by hepatocytes during ischemic stress to activate inflammatory responses during liver I/R. In addition, HMGB1 not only activates inflammatory pathways when released from stressed cells, but it also promotes invasion of tumor cells. We are also examining how HMGB1 induces inflammatory response to promote tumor cell invasion in response to hypoxia. HMGB1 appears to activate downstream TLR4 and RAGE signaling pathways to induce caspase-1 and inflammasome activation to promote cancer metastasis. Further, the systemic release of nuclear HMGB1 is a late event in endotoxin-related lethality in mice. Platinating chemotherapeutics induce DNA lesions that sequester HMGB1 within the nucleus of cells. We are exploring effective strategies to sequester HMGB1 to ameliorate sepsis-related mortality as a novel approach to the treatment of sepsis. Lastly, we are defining a novel role for the transcription factor IRF-1 in regulating apoptosis and autophagy in the setting of endotoxemia and the relationship between IRF-1 and HMGB1 release. 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.

Tsung Team:
Hai Huang, MD
KerryAnn McDonald, MD
Remealle How, MD
Yao Liu, MD
Samer Tohme, MD
Patrick Varley, MD
Daniel Sukato (predoc)
Zachary Dong (predoc)
Katrina Han (predoc)
Alexis Chidi (predoc)
Doris Chen (predoc)
Kim Ferrero, MS
Xinghua Liao, MD
Nicole Martik, BS