Romanian Academy
Catalin Lazar, PhD
Biography
Papers
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. "N-Glycosylation and N-Glycan Processing in HBV Biology and Pathogenesis", Cells 6(9), (2020)
IF: 5.60 -
. "Production of Chimeric Hepatitis B Virus Surface Antigens in Mammalian Cells", Methods in Molecular Biology, Blaine Pfeifer and Andrew Hill (eds.). Springer Science. 2183(Vaccine Delivery Technology: Methods and Protocols), (2020)
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. "Oral administration of a chimeric Hepatitis B Virus S/preS1 antigen produced in lettuce triggers infection neutralizing antibodies in mice", Vaccine 36(38): 5789-5795, (2018)
IF: 3.27 -
. "Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination", Plant biotechnology journal 15(12): 1611-1621, (2017)
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. "Novel function of the endoplasmic reticulum degradation-enhancing α-mannosidase-like proteins in the human hepatitis B virus life cycle, mediated by the middle envelope protein", Cellular microbiology 19(2), (2017)
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. "Characterization of the anti-HBV activity of HLP1-23, a human lactoferrin-derived peptide", Journal of medical virology 85(5): 780-8, (2013)
IF: 2.22AI: 0.70 -
. "Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production", PloS one 7(3): e34169, (2012)
IF: 3.73AI: 1.50 -
. "Antiviral activity of lactoferrin against bovine viral diarrhea virus", Romanian Jornal of Biochemistry(42): 21-29, (2005)
Grants
We aim to produce high yields of novel HBV/HCV antigens with superior immunogenic properties in plants and mammalian cells, based on innovative molecular design and establish in premiere an advanced biotechnological platform for production of best vaccine candidates antigens in algae.
Considering the molecular features of the secretory autophagy, on one hand and the enhanced HBV production by degradation-independent autophagy, on the other hand, we hypothesized that HBV employs this peculiar form of autophagy for its own egress. We further proposed that the M protein plays a pivotal role in tilting the equilibrium between viral degradation and secretion towards the latter, due to the presence of the preS2 domain glycan.
Lactoferrin (Lf), an immunomodulatory glycoprotein was shown to interfere with the life-cycles of many viruses. Our group has rationally designed and characterized the anti-HBV activity of an Lf-derived peptide containing one of the cationic clusters. This project proved the concept that the development of non-toxic, small Lf-derived molecule(s) with a broad-spectrum anti-viral activity may constitute a valuable, cheaper alternative to the current standard of care.
The objectives of this project aim to identify as many as possible cell proteins with a role in processing HBV envelpe proteins and to make a correlation between the HBV cccDNA which is the replicative form of the virus and the expression level of cellular proteins involved in the debradation of the HBV envelope proteins. The results will be confirmed in vivo using human hepatocytes explanted from the patiens chronically infected with HBV.
Degradation of the viral proteins in infected cells is a way to avoid their aberrant accumulation, on one hand, and generate viral peptides, which will be presented at cell surface by the major histocompatibility complex, raising an immune response, on the other hand. In the case of HBV infection, accumulation of mutant viral proteins within the endoplasmic reticulum can result in a particular phenotype, characterised by a ground glass appearance of hepatocytes.