Abstract
The aim of this project is to dissect the changes in the host and viral genomes that enable adenoviral propagation. The project is based on evidence that major alterations in acetylation and methylation patterns of both host and viral genomes are essential for completion of the adenoviral life cycle. Using a combination of inhibitors of histone acetylases and deacetylases, siRNAs and RNAseq analysis the overall goal is to delineate the molecular pathways that are crucial for viral propagation.
References
1 Stella Man YKS, Foster J, Carapuca E, Davies JA, Parker AL, Sosabowski J, Halldén G. Systemic
delivery and SPECT/CT in vivo imaging of 125I-labelled oncolytic adenoviral mutants in models of
pancreatic cancer. Sci Rep (2019) Sep 6;9(1):12840. doi:10.1038/s41598-019-49150-9.
2 Baker AT, Aguirre-Hernandez C, Halldén G, Parker AL. (2018) Designer Oncolytic Adenovirus:
Coming of Age. MDPI Cancers, 10(6)201; https://doi.org/10.3390/cancers10060201
3 Man YKS, Davies JA, Coughlan L, Pantelidou C, Blázquez-Moreno A, Marshall JF, Parker A, Halldén
G. (2018) The novel oncolytic adenoviral mutant Ad5-3Δ-A20T retargeted to αvβ6-integrins efficiently
eliminates pancreatic cancer cells. Molecular Cancer Therapeutics. 17:575-587.
4 Aguirre-Hernández C, Maya-Pineda H, San Millán J, Man YSK, Lu YL, Halldén G. (2018) Sensitisation
to mitoxantrone-induced apoptosis by the oncolytic adenovirus AdΔΔ through Bcl-2-dependent
attenuation of autophagy, Oncogenesis, 7:6.
5 Pantelidou C, Cherubini G, Lemoine NR, Halldén G. (2016) The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11. Oncotarget. Feb 10. PMID:26872382