Boris Yoffe, M.D.
Department of Medicine
Pathogenesis of Virus-Induced Hepatitis
Our laboratory is involved in several basic and clinic research areas devoted to pathogenesis of virus-induced liver diseases:
There is a limited understanding of the cellular regulation of hepatitis B virus (HBV) gene expression in differentiated hepatocytes. We demonstrated that HBV replication inverselycorrelates with cell proliferation and DNA synthesis. In contrast, hepadnavirus replication appears to be enhanced by cell activation and dedifferentiation in non-hepatocytes, including bile duct epithelial and hematopoietic cells.
We hypothesize that HBV gene expression and replication in hepatocytes is regulated in a cell cycle-dependent manner. Recently, we have shown that HBV gene expression is activated in liver-derived cells cultured at low temperature. This model system may be especially useful for future studies that strive to delineate the molecular mechanisms that underlie the relationship between the HBV life cycle and the hepatocyte growth state. The long-term goal of our research is to understand the molecular mechanisms that control viral gene expression and replication at distinct stages of the cell cycle in hepatocytes and extrahepatic cells.
The only available treatment for subjects with end-stage liver disease is liver transplantation. However, due to the shortage of donor livers, there is an urgent need to develop alternative approaches, including liver assist devices, xenotransplantation and hepatocyte transplantation. While these approaches require a readily available pool of primary human hepatocytes, previous efforts have failed to establish long-term cultures of viable and differentiated hepatocytes.
Our preliminary results using a NASA-developed bioreactor that creates the unique environment of low shear force and enables 3-D cell growth demonstrated that a simulated microgravity environment is conducive for maintaining long-term cultures of functional hepatocytes. We observed the formation of liver tissue-like structures (up to 3.0 cm in length) and albumin mRNA was expressed throughout the 60-day culture. The long-term goal is to establish a basis for a potential use of expanded primary hepatocyte cultures in clinical and commercial applications.
We are involved in several clinical and translational studies to understand pathogenesis for HCV- and HBV-induced diseases and to develop better therapy for these conditions.
Department of Medicine
Baylor College of Medicine
One Baylor Plaza, MS BCM385
Houston, TX, 77030, U.S.A.
M.D. - Faculty of Medicine, Technion, Israel
Postdoctoral - Baylor College of Medicine
Ozer A, V.I. Khaoustov, M. Mearns, D. Lewis, G. Darlington and B. Yoffe. Effect of cell proliferation and DNA synthesis on HBV replication. Gastroenterology. 110: 1519-1528, 1996.
Karttunen, R.M. Genta, B. Yoffe, C. Hachem, D.Y. Graham and F. El-Zaatari. Detection of H. pylori in paraffin embedded gastric biopsy specimens by in situ hybridization. Am J Clin Pathol. 106:305-311,1996.
Kazachkov Y., V.I. Khaoustov, B. Yoffe, H. Solomon, G.B.G. Klintmalm and E. Tabor. Hepatocellular carcinoma in the USA: abnormalities of the p53 tumor suppressor gene. Carcinogenesis. 17:2207-2212, 1996.
Kazachkov Y., B. Yoffe, V.I. Khaoustov, H. Solomon, G.B.G. Klintmalm and E. Tabor. Microsatelite instability in human hepatocellular carcinoma: Relationship to p53 abnormalities. Liver, 18:156-161, 1998.
Yoffe B., Darlington G.J., Soriano H.E., Krishnan B., Risin D., Pellis N.R., Khaoustov V.I. Cultures of human liver cells in microgravity environment. Advances in Space Research, 24:829-836, 1999.
Hogue A., Patt Y.Z., B. Yoffe, JD Groopman, M.S. Greenblatt, Y.J. Zhang and R.M. Santella Does Aflatoxin B1 play a role in the etiology of Hepatocellular Carcinoma in the United States. Nutrition and Cancer, 35:27-33, 1999.
Kosovsky MJ, Khaoustov VI, Rushton M, and B. Yoffe. Induction of hepatitis B virus expression at low temperature. Bioch. Bioph. Acta 1490: 63-73, 1999.
Abdel-Fatach G, Yoffe B, Krishnan B, Khaoustov VI, and K. Itani. MDM2/P53 protein expression in colorectal adenocarcinoma. J Gastrointestinal Surg. 4:109-114, 2000.
Khaoustov VI, Risin D, Pellis NR and B. Yoffe. Microarray analysis of genes differentially expressed in HepG2 cells cultured in simulated microgravity. In Vitro cell. & Devel. Biology, 37:84-88, 2001.
Monga H., Rodriguez-Barrades M, Breaux K., Khattak,K, Velez M, Troisi CL and Yoffe B. Increased HCV-related morbidity and mortality in HIV patients. Clin.Inf.Dis., 33:240-247, 2001.
Yoon, D., Kueppers F, Genta RM, Khaoustov, VI., and B. Yoffe, Role of alpha1 antichymotrypsin in promoting cirrhosis in two siblings with heterozygous deficiency phenotype SZ. Gut, 50:730-732, 2002.
Doral A., Genta RM, Goodman Z., and B. Yoffe. Hepatitis C – associated adult idiopathic ductopenia. Dig.Dis.Sci, 47:1625-1626, 2002
Xie Q, Khauostov VI, Chung C, Sohn J., Krishnan B, Lewis D, and Yoffe B. Inhibition of endoplastic reticulum-mediated apoptosis by ursodeoxycholic acid in hepatoma cell lines. Hepatology, 36:592-601, 2002.
Sohn J, Khauostov VI, Xie Q, Chung C Krishnan B, and Yoffe B. Survivin expression and the effects of ursodeoxcholic acid on the survivin in thapsigargin-induced apoptosis. Cancer Letters, 191:83-92,2003.
Yoffe B, Bagri A, Schtenberg K, Khaoustov V and Dural T Hyperlipasemia in patients with hepatitis C infection. Dig Dis Sci, 2003 (in press).