The major focus of our research is on the structure and functions of apoA-I and apoE in relation to the biogenesis of HDL, atherosclerosis and Alzheimer’s disease. Using adenovirus-mediated gene transfer in apoA-I-deficient mice, we have established that apoA-I mutations inhibit discrete steps in a pathway that leads to the biogenesis and remodeling of HDL. To this point, five discrete categories of apoA-I mutants have been characterized that may affect the interactions of apoA-I with ABCA1 or LCAT or may influence the plasma PLTP activity or may cause various forms of dyslipidemia. Biogenesis of HDL is not a unique property of apoA-I. Using adenovirus-mediated gene transfer of apoE in apoA-I- or ABCA1-deficient mice, we have established that apoE also participates in a novel pathway of biogenesis of apoE-containing HDL particles. This process requires the functions of the ABCA1 lipid transporter and LCAT and it is promoted by substitution of hydrophobic residues in the 261 to 269 region of apoE by Ala. The apoE-containing HDL particles formed in the circulation may have atheroprotective properties. ApoE-containing HDL may also have important biological functions in the brain that confer protection from Alzheimer’s disease.
- Professor, Biochemistry, Boston University School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- University of California, Berkeley, PhD
- University of Athens, BS
- Published on 11/4/2017
Zannis VI, Su S, Fotakis P. Role of apolipoproteins, ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins. J Biomed Res. 2017 Nov 04. PMID: 29109329.
- Published on 11/1/2017
Daminelli EN, Fotakis P, Mesquita CH, Maranhão RC, Zannis VI. Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice. Lipids. 2017 Nov 01. PMID: 29094255.
- Published on 11/9/2015
Tamehiro N, Park MH, Hawxhurst V, Nagpal K, Adams ME, Zannis VI, Golenbock DT, Fitzgerald ML. LXR Agonism Upregulates the Macrophage ABCA1/Syntrophin Protein Complex That Can Bind ApoA-I and Stabilized ABCA1 Protein, but Complex Loss Does Not Inhibit Lipid Efflux. Biochemistry. 2015 Nov 24; 54(46):6931-41. PMID: 26506427.
- Published on 9/17/2015
Dafnis I, Metso J, Zannis VI, Jauhiainen M, Chroni A. Influence of Isoforms and Carboxyl-Terminal Truncations on the Capacity of Apolipoprotein E To Associate with and Activate Phospholipid Transfer Protein. Biochemistry. 2015 Sep 29; 54(38):5856-66. PMID: 26337529.
- Published on 8/24/2015
Tiniakou I, Kanaki Z, Georgopoulos S, Chroni A, Van Eck M, Fotakis P, Zannis VI, Kardassis D. Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice. Atherosclerosis. 2015 Nov; 243(1):77-85. PMID: 26363436.
- Published on 5/22/2015
Fotakis P, Kuivenhoven JA, Dafnis E, Kardassis D, Zannis VI. The Effect of Natural LCAT Mutations on the Biogenesis of HDL. Biochemistry. 2015 Jun 2; 54(21):3348-59. PMID: 25948084.
- Published on 4/13/2015
Tiniakou I, Drakos E, Sinatkas V, Van Eck M, Zannis VI, Boumpas D, Verginis P, Kardassis D. High-density lipoprotein attenuates Th1 and th17 autoimmune responses by modulating dendritic cell maturation and function. J Immunol. 2015 May 15; 194(10):4676-87. PMID: 25870241.
- Published on 1/1/2015
Zannis VI, Fotakis P, Koukos G, Kardassis D, Ehnholm C, Jauhiainen M, Chroni A. HDL biogenesis, remodeling, and catabolism. Handb Exp Pharmacol. 2015; 224:53-111. PMID: 25522986.
- Published on 1/1/2015
Kardassis D, Gafencu A, Zannis VI, Davalos A. Regulation of HDL genes: transcriptional, posttranscriptional, and posttranslational. Handb Exp Pharmacol. 2015; 224:113-79. PMID: 25522987.
- Published on 4/28/2014
Fotakis P, Vezeridis A, Dafnis I, Chroni A, Kardassis D, Zannis VI. apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL. J Lipid Res. 2014 Jul; 55(7):1310-23. PMID: 24776540.
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