Of mentors, mentoring, and extracellular matrix

D. Montgomery Bissell – 29 October 2009 – D. Montgomery Bissell briefly describes the way he came to a career in academic medicine, how he found mentors, initial projects, and finally a focus on matrix biology and hepatic fibrosis. He draws some lessons from the experience, which should have relevance for physician‐scientist trainees, those considering that path, anyone with responsibility for training the next generation, institutional leaders, and the National Institutes of Health. (HEPATOLOGY 2009;50:1330–1338.)

Targeting cadherin‐17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma

Ling Xiao Liu, Nikki P. Lee, Vivian W. Chan, Wen Xue, Lars Zender, Chunsheng Zhang, Mao Mao, Hongyue Dai, Xiao Lin Wang, Michelle Z. Xu, Terence K. Lee, Irene O. Ng, Yangchao Chen, Hsiang‐fu Kung, Scott W. Lowe, Ronnie T.P. Poon, Jian Hua Wang, John M. Luk – 29 October 2009 – Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof‐of‐principle studies targeting molecules crucial for the development of HCC.

Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell response that abrogates viral expression in mouse models

Qiang Deng, Maryline Mancini‐Bourgine, Xiaoming Zhang, Marie‐Christine Cumont, Ren Zhu, Yu‐Chun Lone, Marie‐Louise Michel – 29 October 2009 – Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired T cell responses. To ensure active immunotherapy, the immune response must be switched from exhausted T cells to functional effectors that can attain the liver and cure the viral infection. We thus designed a recombinant HBV (rHBV) containing a modified viral core gene that specifically delivers a foreign antigenic polyepitope to the liver.

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma‐glutamyl transpeptidase levels

Robin Haring, Henri Wallaschofski, Matthias Nauck, Marcus Dörr, Sebastian E. Baumeister, Henry Völzke – 29 October 2009 – The aim of the present study was to investigate the association of serum gamma‐glutamyltransferase (GGT) levels with all‐cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population‐based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis.

Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1

Dineke E. Folmer, Vincent A. van der Mark, Kam S. Ho‐Mok, Ronald P.J. Oude Elferink, Coen C. Paulusma – 29 October 2009 – Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1), forming a spectrum of cholestatic disease. Whereas PFIC1 is a progressive, endstage liver disease, BRIC1 patients suffer from episodic periods of cholestasis that resolve spontaneously. At present it is not clear how the type and location of the mutations relate to the clinical manifestations of PFIC1 and BRIC1.

Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice

Nora Bijl, Milka Sokolović, Carlos Vrins, Mirjam Langeveld, Perry D. Moerland, Roelof Ottenhoff, Cindy P. A. A. van Roomen, Nike Claessen, Rolf G. Boot, Jan Aten, Albert K. Groen, Johannes M. F. G. Aerts, Marco van Eijk – 29 October 2009 – Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver.

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