Laboratory of Liver Diseases Group Photo

 

June 2012

Bin Gao MD. , PhD, Chief

Laboratory of Liver Diseases

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

5625 Fishers Lane, Room 2S-33

Bethesda, MD 20892

telephone: 301.443.3998; fax: 301 480.0257

e-mail: bgao@mail.nih.gov                           

 

Hua Wang, MD., PhD

(Research Fellow, email:  whua@mail.nih.gov)

 

Ogyi Park, PhD

(Research Fellow, email: parkogyi@mail.nih.gov)
 

Adeline Bertola, PhD

(Visiting Fellow, email: adeline.bertola@nih.gov)
 

Dechun Feng, PhD

(Visiting Fellow, email: dechun.feng@nih.gov)

 

Hyojung Kwun, DMV, PhD

(Visiting fellow, email: hyojung.kwun@nih.gov)
 

Young Suk Won, PhD

(Visiting Fellow, email: youngsuk.won@nih.gov)
 

Mingjiang Xu, MD., PhD

(Visiting fellow, email: ming-jiang.xu@nih.gov)

 

Stephanie Mathews, PhD

(Postdoctoral fellow, email: stephanie.mathews@nih.gov)
 

Yan Wang, MD PhD

(Guest researcher, email: yan.wang7@nih.gov)
 

Yongmei Li, MD., PhD

(Special Volunteer, email: yongmei.li@nih.gov)

 

Xiaoni Kong, PhD

(Former Visiting fellow, current address, Med-X Research Institute, Shanghai Jiao Tong University, email: xiaonikong@gmail.com)

 

Vadalia, Shalini

(Summer student)

 

Mission Statement:

 

The mission of the Laboratory of Liver Diseases at NIAAA, NIH, established in 2009, is to investigate the immunological aspects and molecular pathogenesis of alcoholic liver disease (ALD), and to explore novel therapeutic targets for the treatment of this disorder. ALD is a major cause of chronic liver disease, leading to cirrhosis and liver cancer. The latest report from our institute (NIAAA) shows that cirrhosis is the 12th leading cause of deaths in the United States with a total of 29,925 deaths in 2007, of which 48.1% were alcohol-related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma. At present, there are no small animal models available for human alcoholic hepatitis (inflammation), cirrhosis, and alcoholic liver cancer. Thus, our laboratory has been actively using liver injury models induced by ethanol and other insults to investigate the immunologic mechanisms underlying alcoholic liver injury, to study the effect of inflammation on liver disease progression, and to explore novel therapeutic targets for the treatment of ALD. Currently, we are focusing on the roles of innate immune cells (eg. natural killer and natural killer T cells), cytokines (eg. interleukin-6, interleukin-22), and the Jak-STAT signaling pathways activated by these cytokines in liver injury, fibrosis, regeneration, progenitor/stem cell proliferation, and hepatocarcinogenesis. We are also exploring the therapeutic potential of interleukin-22 for the treatment of ALD.

 

 

Selected Recent Publications (over 160)

 

Review articles:

 

  1. Gao, B., Lafdil, F., Wang, H., Feng, D.: The STAT proteins: key regulators of antiviral response, inflammation and tumorigenesis in the liver. Journal of Hepatology 2012, 57:430-41
  2. Wang, H., Gao, B., Zakhari, S., and Nagy, L.: Inflammation in alcoholic liver disease. Annual Reviews of Nutrition 2012, 32:343-68
  3. Gao, B., Bataller, R.: Alcoholic liver disease: pathogenesis and new therapeutic targets    Gastroenterology 2011,141:1572-1585
  4. Gao, B., Radaeva, S., Park, O.: Liver NK/NKT cells: Immunobiology and emerging roles in liver diseases. J. Leukocyte Biology 2009; 86:513-528
  5. Gao, B., Jeong, W., and Tian, Z.: Liver: an organ with predominant innate immunity.   Hepatology 2008; 47:729-736

 

Original Articles:

 

  1. Kong, X., Feng, D., Wang, H., Hong, F., Bertola, A., Wang, F., and Gao, B.: IL-22 induces hepatic stellate cell senescence and restricts liver fibrosis. Hepatology 2012 in press
  2. Feng, D., Kong, X., Weng, H., Park, O., Wang, H., Dooley, S., Gershwin, E., and Gao, B.: IL-22 promotes liver progenitor cell proliferation in patients with viral hepatitis and in mice. Gastroenterology 2012 143:188-198
  3. Park, O., Wang, H., Weng, H., Feigenbaum, L., Li, H., Yin, S., Ki, S., Yoo, S., Dooley, S., Wang, F., Young, S., and Gao, B.:  In vivo consequences of liver-specific IL-22 expression: implications for human liver disease progression. Hepatology, 2011, 54:252-261
  4. Miller, A., Wang, H., Park, O., Horiguchi, N., Ki, S., Yin, S., Lafdil, F., and Gao, B.: Inflammation-associated hepatic IL-6/STAT3 activation ameliorates alcoholic and nonalcoholic fatty liver diseases in IL-10 deficient mice. Hepatology 2011 54:846-856
  5. Li, Y.,  Xu, S., Mihaylova, M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, E.,  Shyy, J., Gao, B., Wierzbicki, M., Verbeuren, T., Shaw, R., Cohen, R., Zang, M.: AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice. Cell Metabolism 2011, 13:376-88
  6. Jeong, W., Park, O., Wang, L., Suh, Y., Byun, J., Park, S., Kim, J., Ko, H., Wang, H., Miller, A. and Gao, B.: Suppression of innate immunity (NK cells and IFN-g) in the late stages of liver injury. Hepatology 2011, 53:1342-1351
  7. Zhang, Z., Zhang, S., Zou, Z., Fan, R., Zhao, J., Li, B., Fu, J., Li, Z., Qin, E., Xu, X., Zhang, J., Zhou, C., Shi, M., Gao, B., Tian, Z., Wang, F.: Roles of NK cells in liver injury and fibrosis in patients with chronic HBV infection. Hepatology 2011, 53:73-85
  8. Ki, S., Park, O., Zheng, M., Kolls, J., Batller, R., and Gao, B.: IL-22 treatment ameliorates alcoholic liver injury in a murine model of chronic plus binge drinking. Hepatology 2010, 52:1291-300
  9. Zhang. X., Tachinana, S., Wang, H., Williams, G., Gao, B., and Sun, Z.: IL-6 is an essential mediator for mitochondrial DNA repair in alcoholic liver injury in mice. Hepatology 2010, 52:2137-2147
  10. Kim H, Xiao C, Wang R, Lahusen T, Xu X, Vassilopoulos A, Vazquez-Ortiz G, Jeong W, Park O, Ki S, Gao B, Deng CX.: Sirt6 deacetylase negatively regulates glycolysis and triglyceride synthesis and prevents fatty liver formation in mice. Cell Metabolism 2010, 12:224-236
  11. Horiguchi N, Lafdil F, Miller AM, Park O, Wang H, Rajesh M, Mukhopadhyay P, Fu X, Pacher P, Gao, B.: Dissociation between hepatic inflammation and necrosis induced by CCl4 in myeloid cell specific STAT3 knockout mice.   Hepatology 2010, 51:1724-34
  12. Wang, H., Lafdil, F., Park, O., Shen, K., Horiguchi, N., Yin, S., Fu, X., Kunos, G., Gao, B.: Interplay of hepatic and myeloid STAT3 in facilitating liver regeneration via tempering innate immunity.  Hepatology 2010, 51:1354-1362
  13. Hong, H., Mak, K., Topol, L., Yun, K., Hu, J., Garrett, L., Chen, Y., Park, O., Chang, J., Simpson, R., Wamg, C., Gao, B., Jiang, J., Yang, Y.: Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci USA 2010, 107:1431-6
  14. Park, O., Jeong, W., Wang, L., Wang, H., Lian, Z., Gershwin, E., and Gao, B: Diverse roles of invariant NKT cells in liver injury and fibrosis induced by carbon tetrachloride.    Hepatology 2009, 47:571-580
  15. Lafdil, F., Wang, H., Park, O., Zhang, W., Moritoki, Y., Fu, X., Gershwin, M., Lian, Z., Gao, B.: Myeloid STAT3 inhibits T-cell-mediated hepatitis by regulating T helper 1 cytokine and interleukin-17 production. Gastroenterology 2009, 137:2125-35
  16. Horiguchi, N., Wang, L., Mukhopadhyay, P., Jeong, W., Lafdil, F., Osei-Hyiaman, D., Moh, A., Fu, X., Pacher, P., Kunos, G., Gao, B.: Cell-dependent pro- and anti-inflammatory role of STAT3 in alcoholic liver injury. Gastroenterology 2008;134:1148-1158
  17. Jeong, W., Park, O., Gao, B.:  Abrogation of anti-fibrotic effects of NK/IFN-g contributes to alcohol acceleration of liver fibrosis. Gastroenterology 2008, 134:248-258
  18. Hu, W., Ferris, S., Tweten, R., Wu, G., Radaeva, S., Gao, B., Bronson, R., Halperin, J., Qin, X.:  Conditional, rapid and targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nature Medicine 2008;14, 98 – 103
  19. Jeong W, Osei-Hyiaman, D., Park, O., Liu, J., Bátkai, S., Mukhopadhyay, P., Horiguchi, N., Harvey-White, J., Marsicano, G., Lutz, B., Gao, B., Kunos, G.: Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic liver disease. Cell Metabolism 2008; 7:227-35.
  20. Chuang, Y., Lian, Z., Yang, G., Shu, S., Moritoki, Y., Ridgway, M., Kronenberg, M., Flavell, R., Gao, B., and Gershwin, E.: CD1d-restricted NKT cells exacerbate liver injury in a TGF-b receptor II dominant-negative mouse model of primary biliary cirrhosis. Hepatology 2008;47:571-580
  21. Cui, Y., Hosui, A., Sun, R., Shen, K., Gavrilova, O., Chen, W., Cam, M., Gao, B., Robinson, G., Hennighausen, L.: Inactivation of hepatic Stat5a/b results in aberrant GH-induced activation of Stat1 and Stat3, hepatosteatosis, and diminished liver regeneration.  Hepatology 2007;46:504-513
  22. Sun R., Park, O., Horiguchi, N, Kulkarni, S., Jaruga, B., Jeong, W., Sun, H., Radaeva, S., and Gao, B:. STAT1 contributes to dsRNA inhibition of liver regeneration after partial hepatectomy in mice.  Hepatology 2006, 44:955-966
  23. Jeong, W., Park, O., Radaeva, S., and Gao, B: STAT1 inhibits liver fibrosis through attenuating stellate cell activation and stimulating NK cell killing of activated stellate cells. Hepatology 2006, 44:1441-1451
  24. Radaeva, S., Sun, R., Jaruga, B., Nguyen, V., Tian, Z., Gao B.: Natural killer cells ameliorate liver fibrosis through killing activated stellate cells in RAE1/NKG2D- and TRAIL-dependent manners. Gastroenterology 2006, 130: 435-452.
  25. Xu, X., Kobayashi, S., Qiao, W., Li, C., Xiao, C., Radaeva, S., Stiles, B., Wang, R., Ohara, N., Yoshino, T., LeRoith, D., Torbenson, M., Gores, G., Wu, H., Gao, B., and Deng, C. Induction of cholangiocellular carcinoma by liver specific disruption of Smad4 and Pten in mice.  J. Clin. Invest. 2006, 116:1843-1852
  26. Kim, W., Lee, J., Suh, Y., Hong, S., Choi, J., Lim, J., Song, J., Gao, B., and Jung, M.: Exposure to chronic high glucose induces b-cell apoptosis through decreased interaction of GCK with mitochondria: downregulation of GCK in pancreatic b cells. Diabetes 2005,54:2602-11
  27. Sun R., and Gao, B.: Negative regulation of liver regeneration by innate immunity (NK/IFN-g). Gastroenterology 2004, 127, 1525-1539
  28. Radaeva, R., Sun, R., Pan, H., Hong, F., and Gao, B.: Interleukin-22 (IL-22) plays a protective role in T cell hepatitis: IL-22 is a survival factor for hepatocytes via activation of STAT3. Hepatology 2004, 39:1332-1342.
  29. Hong, F., Radaeva, S., Pan, H., Tian, Z., Veech, R., and Gao, B.: Interleukin-6 treatment alleviates steatosis and ischemia/reperfusion injury in mice with fatty liver disease. Hepatology 2004, 40: 933-941.
  30. Gao, B., Hong, F., and Radaeva, S: Host factors and interferon-a treatment failure in HCV: molecular mechanisms and potential therapeutic improvement (Review). Hepatology 2004, 39:880-890.
  31. Jaruga, B., Hong, F., Sun, R., Radaeva, S., and Gao, B.: Crucial Role of IL-4/STAT6 in T cell-mediated hepatitis: Upregulating eotaxins and IL-5, and recruiting leukocytes. J. Immunol.  2003, 171: 3233-3244  
  32. Sun, Z., Klein, A. S., Radaeva, S., Hong, F., El-Assal, O., Jaruga, B., Pan, H., Batkai, S., Tian, Z., Hoshino, S., Kunos, G., Diehl, A., and Gao, B.: In vitro interleukin-6 treatment prevents mortality associated with fatty liver transplants in rats. Gastroenterology 2003, 125:202-215.
  33. Radaeva, S., Jaruga, B., Hong, F., Kim, W. H., Fan, S., Cai, H., Strom S., Liu, Y., El-Assal, O., and Gao, B.: Interferon-a activates multiple STAT signals and downregulates c-Met in primary human hepatocytes. Gastroenterology 2002, 122:1020-1034.
  34. Nguyen, V. N., and Gao, B.: Expression of interferon-a signaling components in human alcoholic liver disease. Hepatology  2002, 35:425-432.
  35. Hong, F., Kim, W. H., Tian, Z., Jaruga, B., Ishac, E., Shen, X., and Gao, B.: Elevated IL-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of Bcl-2 and Bcl-x(L) proteins. Oncogene  2002, 21:32-43.
  36. Hong, F., Jaruga, B., Kim, W. H., Radaeva, S., Tian, Z., El-Assal, O., Nguyen, V., and Gao, B.: Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. J. Clin. Invest.  2002, 110: 1503-1513.

 

Editorials

 

  1. Gao, B., and Waisman A.:  Th17 cells regulate liver fibrosis by targeting multiple cell types: Many birds with one stone.  Gastroenterology 2012, in press
  2. Gao, B., and Bertola A.: Natural killer cells take two Tolls to destruct bile ducts. Hepatology  2011, 53:1076-1079
  3. Gao, B.: Innate immunity and steatohepatitis: A critical role of another Toll (TLR9). Gastroenterology 2010, 139:27-30
  4. Gao, B.: NKG2D, its ligands and liver disease – good or bad?  Hepatology 2010, 51:8-11
  5. Danese, S., and Gao, B.: IL-6: A therapeutic Jekyll and Hyde in gastrointestinal and hepatic diseases. Gut 2010, 59:149-151
  6. Kunos, G., and Gao, B.: Endocannabinoids, CB1 receptors, and liver disease – hitting more than one bird with the same stone.  Gastroenterology 2008;134:622-625
  7. Kunos, G., Osei-Hyiaman, D., Bátkai, S., and Gao, B.: Cannabinoids hurt, heal in cirrhosis. Nature Medicine 2006, 12:608-610