Liver diseases are among the 10 leading causes of death in the United States. The liver's extraordinary regenerative capacity is critical to understanding the mechanisms leading to developmental defects, acute and chronic liver diseases, and liver carcinogenesis. Stimulation of hepatocyte proliferation while preventing apoptosis is essential to the liver's regenerative process. Recently we uncovered a tumor suppressor pathway has potent effects upon liver cell division and death. Our long range goal is to define the cellular mechanisms underlying liver regeneration in health and disease and to apply these findings to developing improved therapies for liver disease. To that end, we are uniquely capable to address the objectives of this application, which are to uncover the mechanism that leads to the novel tumor suppressors'profound effects upon the liver. The central hypothesis of this proposal is that: The tumor suppressor controls liver celgrowth factor pathway in controlling liver size. At the end of the study we will better understand the growth and death of liver cells. This will help develop treatment for many liver diseases such as liver transplantation, cirrhosis, acute and chronic hepatitis.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Gastrointestinal Cell and Molecular Biology Study Section (GCMB)
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Serrano, Jose
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Johns Hopkins University
Schools of Medicine
United States
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Iansante, Valeria; Choy, Pui Man; Fung, Sze Wai et al. (2015) PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation. Nat Commun 6:7882
Gurda, Grzegorz T; Zhu, Qingfeng; Bai, Haibo et al. (2014) The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease. Hum Pathol 45:1057-64
Sauter, Jennifer L; Nayar, Suresh K; Anders, Paige D et al. (2013) Co-existence of Sarcina Organisms and Helicobacter pylori Gastritis/Duodenitis in Pediatric Siblings. J Clin Anat Pathol (JCAP) 1:
Sun, Hai-Xiang; Xu, Yang; Yang, Xin-Rong et al. (2013) Hypoxia inducible factor 2 alpha inhibits hepatocellular carcinoma growth through the transcription factor dimerization partner 3/ E2F transcription factor 1-dependent apoptotic pathway. Hepatology 57:1088-97
Lipson, Evan J; Vincent, Jeremy G; Loyo, Myriam et al. (2013) PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res 1:54-63
Robertson, Scott; Hyder, Omar; Dodson, Rebecca et al. (2013) The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome. Hum Pathol 44:2768-73
Xu, Yang; Chenna, Venugopal; Hu, Chaoxin et al. (2012) Polymeric nanoparticle-encapsulated hedgehog pathway inhibitor HPI-1 (NanoHHI) inhibits systemic metastases in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 18:1291-302
Bai, Haibo; Zhang, Nailing; Xu, Yang et al. (2012) Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology 56:1097-107
Levy, Mary; Trivedi, Anand; Zhang, Jun et al. (2012) Expression of glypican-3 in undifferentiated embryonal sarcoma and mesenchymal hamartoma of the liver. Hum Pathol 43:695-701
Taube, Janis M; Anders, Robert A; Young, Geoffrey D et al. (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127ra37

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