Honglei Weng, PhD

Research topic

My research is mainly focused on understanding the molecular mechanism of fibrosis and cirrhosis in different chronic liver diseases and how fibrosis/cirrhosis contribute to primary liver cancer, including hepatocellular carcinoma and cholangiocarcinoma. Liver fibrosis is the common pathway leading to liver cirrhosis for any kind of chronic liver diseases. More than half of hepatocellular carcinoma and a part of cholangiocarcinoma derive from liver cirrhosis. Fibrotic tissue remodelling of liver architecture can influence liver cancer metastasis and accelerate chronic graft rejection in liver transplant recipients. Until now, no standard treatment of chronic liver diseases was proven in clinical trials.

Acute-on-chronic liver failure (ACLF) is a new identified disease entity and is characterized as acute deterioration of hepatic functions, multiple organ failure and deranged systemic inflammatory responses. The disease occurs at the patients who have chronic liver disease, particularly liver cirrhosis. The short mortality of ACLF reaches 50%. Massive hepatic necrosis is the major histological feature of this severe liver disease. In the condition of massive hepatic necrosis, liver progenitor cells (LPC)-derived liver regeneration determine clinical outcome of the ACLF patients in most cases. We are interested in elucidating molecular and immunological mechanisms of the LPC-dependent liver regeneration.

My current specific aims include the following:

1. Identify different signaling pathways (e.g., TGF-β) dependent and independent pro-fibrogenic mechanisms in different chronic liver diseases.
2. Characterize the predominant signaling pathways in liver progenitor cell-dependent liver regeneration in ACLF.

Selected publication from recent five years:

1. Shen Z, Liu Y, Dewidar B, Hu J, Park O, Feng T, Xu C, Yu C, Li Q, Meyer C, Ilkavets I, Müller A, Stump-Guthier C, Munker S, Liebe R, Zimmer V, Lammert F, Mertens PR, Li H, ten Dijke P, Augustin HG, Li J, Gao B, Ebert MP, Dooley S, Li Y, Weng HL. Delta like ligand 4 modulates liver damage by downregulating chemokine expression. Am J Pathol 2016;186:1874-1889. doi: 10.1016/j.ajpath.2016.03.010.
2. Weng HL, Cai X, Yuan X, Liebe R, Dooley S, Li H, Wang TL. Two sides of one coin: hepatic necrosis and progenitor cell-derived regeneration in acute liver failure. Frontiers in Physiology 2015; doi: 10.3389/fphys.2015.00178.
3. Li H, Xia Q, Zeng B, Li ST, Liu H, Li Q, Li J, Yang SY, Dong XJ, Gao T, Munker S, Liu Y, Liebe R, Xue F, Li QG, Chen XS, Liu Q, Zeng H, Wang JY, Xie Q, Meng QH, Wang JF, Mertens PR, Lammert F, Singer MV, Dooley S, Ebert MP, Qiu K, Wang TL, Weng HL. Submassive hepatic necrosis distinguishes HBV-associated acute-on-chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol 2015;63:50-59. doi: 10.1016/j.jhep.2015.01.029.
4. Yin CH, Weng HL, Zhou FG, Fang M, Ji J, Cheng C, Wang H, Liebe R, Dooley S, Gao CF. Elevated core-fucosylated IgG is a new diagnostic and longitudinal monitoring marker in HBV-related hepatocellular carcinoma. OncoImmunology 2015 Jul 7;4(12):e1011503. eCollection 2015 Dec.
5. Xu C, Wan X, Xu L, Weng H, Yan M, Miao M, Sun Y, Xu G, Dooley S, Li Y and Yu C. Xanthine oxidase in nonalcoholic fatty liver disease and hyperuricemia: one stone hits two birds. J Hepatol. 2015;62(6):1412-9. doi: 10.1016/j.jhep.2015.01.019. Epub 2015 Jan 23.
6. Feng D, Wang Y, Wang H, Weng H, Kong X, Martin-Murphy BV, Li Y, Park O, Dooley S, Ju C, Gao B. Acute or chronic effects of IL-22 in acetaminophen-induced liver injury. J Immunol 2014; Sep 1;193(5):2512-8. doi: 10.4049/jimmunol.1400588.
7. Weng HL, Feng DC, Radaeva S, Kong XN, Wang L, Liu Y, Li Q, Shen H, Gao YP, Müllenbach R, Munker S, Huang T, Chen JL, Zimmer V, Lammert F, Merten PR, Cai WM, Dooley S and Gao B. Interferon gamma inhibits liver progenitor cell proliferation in patients with chronic hepatitis B and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice. J Hepatol 2013;59: 738-45. doi:pii: S0168-8278(13)00374-7. 10.1016/j.jhep.2013.05.041.
8. Feng D, Kong X, Weng H, Park O, Wang H, Dooley S, Gershwin ME, Gao B. Interleukin-22 promotes liver stem/progenitor proliferation in the mice and patients with chronic hepatitis B infection. Gastroenterology 2012;143: 188-198.e7
9. Liu Y, Meyer C, Müller A, Herweck F, Li Q, Meullenbach R, Mertens PR, Dooley S and Weng H-L. IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-b independent Smad signalling. J Immunol 2011;187:2814-2823. 187:.doi/10.4049/jimmunol.1003260
10. Park O, Wang H, Weng H, Feigenbaum L, Li H, Yin S, Ki SH, Yoo SH, Dooley S, Wang FS, Young HA and Gao B. In vivo consequences of liver specific interleukin-22 expression: implications for human liver disease progression. Hepatology 2011;54:252-261.