Vassilis I. Zannis
Professor of Biochemistry
Departments of Medicine and Biochemistry
Boston University School of Medicine
Center for Advanced Biomedical Research Building, W509
700 Albany Street
Boston, MA 02118
Phone: 617-638-5085
Fax: 617-638-5141
Email: vzannis@bu.edu
Education
Ph.D., Department of Biochemistry, University of California, Berkeley, CA
Research Interest
Lipoproteins are macromolecular complexes of lipids and apolipoproteins, which are involved in cholesterol transport and cholesterol homeostasis. During the past 15 years our laboratory has cloned most of the apolipoprotein cDNAs and/or genes and has described genetic variations in apolipoproteins that are associated with human diseases. We have also identified the regulatory elements which are involved in the regulation of transcription of the apoA-I, apoA-II, apoA-IV, apoB, apoCII and apoCIII genes and several factors bound to them, and have assessed their importance for hepatic and intestinal transcription. Currently, we have two major research objectives: I. Mechanisms of transcriptional regulation of the apolipoprotein genes in vivo and in vitro. This includes a) elucidation of the role of hormone nuclear receptors and factors bound to the apoCIII enhancer on the transcriptional regulation of the apoA-I, apoCIII, and apoA-IV gene cluster; b) elucidation of the importance of the hormone nuclear receptors and apoCIII enhancer for apolipoprotein gene regulation in vivo using in vivo footprinting, antisense methodologies, and transgenic mice. The combined in vitro and in vivo approaches may provide new insights on the mechanisms responsible for apolipoprotein gene regulation that may affect the plasma apolipoprotein and lipoprotein levels. II. Elucidation of the structure-function relationship of human apoA-I and apoE. a) by in vitro mutagenesis of the corresponding genes and analysis of the properties of the protein products; and b) by using transgenic methodologies. ApoA-I is involved in the reverse transport of cholesterol and the activation of the enzyme LCAT. ApoE is responsible for the clearance of lipoprotein remnants and recently has been implicated in Alzheimer’s disease. Pertinent questions are: domains of the two proteins involved in lipid and receptor binding, in activation of enzymes, as well as the role of apoE in the pathogenesis of Alzheimer’s disease.
Representative Publications
Laccotripe, M., Makrides, S.C., Jonas, A., and Zannis, V.I. (1997).The carboxyl-terminal hydrophobic residues of apolipoprotein A-I affect its rate of phospholipid binding and its association with high density lipoprotein. J. Biol. Chem. 272:17511-17522.
Kardassis, D., Saccharidou, E. and Zannis, V.I. (1998).Transactivation of the human apolipoprotein CII promoter by orphan and ligand-dependent nuclear receptors. J. Biol. Chem. 273:17810-17816.
Aleshkov, S.A., Abraham, C.R., and Zannis, V.I. (1997). Interaction of nascent apoE2, apoE3, and apoE4 isoforms expressed in mammalian cells with amyloid peptide b (1-40). Relevance to Alzheimer’s disease. Biochemistry 36:10571-10580.
Liadaki, K.N., T. Liu, S. Xu, B.Y. Ishida, J.P. Krieger, J. Kane, M., Krieger, V.I. Zannis. (2000) Binding of HDL and rHDL to the HDL receptor SR-BI: Effect of lipid association and apoA-I mutations on receptor binding. J. Biol. Chem. 275: 21262-21271
Kan, H.-Y., S. Georgopoulos, V.I. Zannis. (2000) A hormone response element in the human apoCIII enhancer is essential for intestinal expression of the apoA-I and apoCIII genes and contributes to the hepatic expression of the two linked genes in transgenic mice. J. Biol. Chem. (in press)
