Yasuko Iwakiri, PhD

Vascular biology of the liver:

My lab has been committed to working on the lymphatic system in the liver, which is a very unexplored area in the study of liver biology (Chung & Iwakiri, CMH, 2013; Iwakiri, Hepatology, 2016; Tanaka & Iwakiri, CMGH, 2016).

Liver fibrosis:

1. We investigate the role of each major liver cell type in fibrogenesis with a particular interest in hepatic stellate cells (HSC), a cell type that has the most direct impact on the development of fibrosis. We have determined that a protein called Reticulon 4B (a.k.a., Nogo-B) increases fibrosis by promoting collagen production by HSCs (Zhang et al., Hepatology, 2011) and protecting HSCs from apoptosis (Tashiro et al., Am J Pathol, 2013).
2. In collaboration with Dr. Mark Saltzman (Yale University), we have explored the therapeutic potential of targeting Reticulon 4B in HSCs for liver fibrosis by delivering siRNA encapsulated in nanoparticles. While nanoparticles have been considered an important tool for delivery of drugs and the liver has been known to retain nanoparticles, their cellular distribution in the liver was not clearly understood. We conducted extensive analyses of liver cell uptake of nanoparticles and demonstrated their cellular distribution in vivo for the first time (Park et al., Nanomedicine, 2016). This study is significant since the effectiveness and safety of medical application of nanoparticles for liver therapy depends on their specific delivery to targeted cell populations.

Kupffer cells/macrophages in the pathogenesis of alcohol-induced liver disease:

Alcohol abuse causes liver disease, whose spectrum includes alcoholic fatty liver, alcoholic hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma in a progressive manner. Early intervention may prevent progression to cirrhosis and hepatocellular carcinoma, but effective treatments are limited due to our incomplete understanding of the molecular and cellular mechanisms of alcohol-induced liver injury. My lab studies the mechanism of alcohol-induced liver injury, in which Kupffer cells (liver resident macrophages) have a pivotal role. We also explore therapeutic potential of nanoparticle delivery to Kupffer cells for the treatment of alcoholic liver disease.