Research Interests

Molecular mechanisms whereby alcohol and its metabolites induces liver fibrosis and cirrhosis; Cell-cell and cell-matrix interaction Development of co-culture systems to sustain hepatocyte survival and differentiation; and the role of cell-surface laminin-binding proteins in tumor adhesion, invasion and metastasis, and investigate drug toxicity and infection with hepatitis C virus.

Research Program

Liver cirrhosis is the 12th leading cause of death in the United States and the 4th when considering males between 45 to 54 years of age. Close to 50% of these deaths are associated with chronic alcohol consumption and the other 50% to multiple causes of which chronic hepatitis B and C are predominant. There is no approved therapy for this deadly disease. A better understanding of the molecular mechanisms whereby alcohol and its metabolites and HBV/HCV induce liver fibrosis will allow the development of novel therapies for these end-stage liver diseases. Our studies on the role of oxidative stress have lead to the finding of a chemokine with great antifibrogenic potential in vitro.

Studies of chronic alcohol toxicity and HCV infection in vitro have been hampered by the lack of appropriate methods to sustain hepatocyte differentiation in culture. We have developed a co-culture system of hepatocytes and hepatic stellate cells that sustains hepatocyte differentiation in culture, for at least 5 months. These co-cultures metabolize ethanol, can be infected with HCV and survive when implanted into scid mice.

Normal and tumor cells attach to laminin using integrin and non-integrin receptors. Normal hepatocytes contain a very high affinity laminin-binding protein that differs from that present in hepatomas. This protein of normal hepatocytes prevents tumor attachment in vitro and tumor implantation in the liver in vivo.

Selected Publications

• Sicklick JK, Choi SS, Bustamante M, McCall SJ, Hernandez Perez E, Huang J, Li YX, Rojkind M, Diehl AM. Evidence for Epithelial-Mesenchymal Transitions in Adult Liver Cells. Am J Physiol Gastrointest Liver Physiol. 291: G575-G583, 2006.
• Zhang Y, Ikegami T, Honda A, Miyazaki T, Bouscarel B, Rojkind M, Hyodo I, Matsuzaki Y. Involvement of integrin-linked kinase in carbon tetrachloride-induced hepatic fibrosis in rats., Hepatology 44:612-622, 2006.
• Lechuga CG, Hernandez-Nazara ZH, Hernandez E, Bustamante M, Desierto G, Cotty A, Dharker N, Choe M, Rojkind M. PI3 Kinase is involved in PDGF-{beta} receptor up-regulation post-PDGF-BB treatment in mouse hepatic Stellate cells. Am J Physiol Gastrointest Liver Physiol. 291: G1051-G1061, 2006.
• Nieto, N and Rojkind, M: Repeated whiskey binges promote liver injury in rats fed a choline-deficient diet J. Hepatol. 46: 330-339, 2007.
• Trujillo-Murillo K, Rincón-Sánchez AR, Martínez-Rodríguez H, Bosques-Padilla F, Ramos-Jiménez J, Barrera-Saldaña HA, Rojkind M, Rivas-Estilla AM. Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways. Hepatology 47:1462-1472, 2008.
• Olga Ohayon, Nidal Mawasi, Anna Pevzner, Ana Tryvitz, Tsvia Gildor, Mark Pines, Marcos Rojkind, Melia Paizi and Gadi Spira. Halofuginone upregulates the expression of heparanase in thioacetamide-induced liver fibrosis in rats. Lab Invest. 88:627-633, 2008.