Research Interests

Keywords

Portal hypertension; vascular biology of the liver; lymphangiogenesis; liver fibrosis; liver cirrhosis; liver regeneration; Nogo-B; reticulon 4B; nitric oxide signaling

Portal hypertension and vascular biology of the liver

Portal hypertension

Portal hypertension is one of the most detrimental complications of liver diseases. Our goal is to understand the mechanisms of portal hypertension in liver cirrhosis and develop therapies that ameliorate detrimental consequences, such as varices and ascites, associated with portal hypertension.

Lymphangiogenesis

Lymphangiogenesis is the growth of lymphatic vessels. Any changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. We are interested in how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases.

Liver fibrosis/cirrhosis/regeneration

Currently there is no effective treatment for liver fibrosis. Furthermore, liver cirrhosis, an advanced stage of fibrosis, is the major cause of portal hypertension. Our goal is to understand mechanisms of liver fibrosis and cirrhosis and develop potential therapeutic strategy to decrease liver fibrosis/cirrhosis.

Nogo-B/reticulon-B

Our recent studies showed Nogo-B, a.k.a., reticulon 4B, promotes liver fibrosis/cirrhosis and the development of portal hypertension. Further, we showed that absence of Nogo-B ameliorates liver cirrhosis and blocks portal hypertension (Zhang et al. (2011), Hepatology). Importantly, absence of Nogo-B decreases liver fibrosis by impairing TGFbeta/Smad2 signaling pathway (Zhang et al. (2011), Hepatology) and increasing apoptosis in myofibroblasts derived from hepatic stellate cells (Tashiro et al. (2013),Am J of Pathology). In addition to its role in liver fibrosis/cirrhosis, Nogo-B plays an important role in liver regeneration. We showed that lack of Nogo-B delays liver regeneration (Gao et al. (2013,) Hepatology).