Chemotherapy and radiation induce cancer cell death through DNA damage; however, the prevalence of drug-resistant cancer presents a substantial treatment barrier. Previous investigations have connected the overexpression of DNA dependent protein kinase (DNA-PK), a crucial enzyme in the DNA damage response (DDR), to chemotherapy resistant cancer cells. There has been much evidence to indicate that […]
C09: Elucidating Interactions between Adenovirus and DNA- PK
For Adenovirus (Ad) to undergo a successful replication cycle, proteins expressed from the early gene region 4 (E4) function in regulating the host’s DNA damage response (DDR). In mutant viruses with a deletion of the E4 region (E4-), one particular DDR kinase — DNA-dependent protein kinase (DNA-PK)— is able to ligate the ends of Ad […]
C10: Determining How Activation of the DNA-Dependent Protein Kinase Impacts Adenovirus Replication
While human adenovirus (Ad) infection can cause severe illness, antiviral treatments often cause serious adverse effects and have limited efficacy against severe Ad infection. Ad infection activates the cellular DNA damage response (DDR), which triggers activation of protein complexes such as the DNA-dependent protein kinase (DNA-PK) that hinder viral infection. However, Ad wields several viral […]
C34: Engineering an Oncolytic Adenovirus Containing HMGA1-Antisense for Treatment of Pancreatic Cancer
Being one of the major cancers with the highest mortality rate and lowest 5-year survival rate, pancreatic cancer is growingly concerned world-wide. Recurrence rate after surgery is still high. Therefore, safe, affordable, and effective therapies are increasingly needed for a better outcome. The main objective of this project is to engineer an oncolytic adenovirus with […]
A04-P: Evaluating How Adenovirus Proteins Regulate DNA-PK
Adenovirus (Ad) infection can lead to the activation of DNA damage response (DDR) pathways such as non-homologous end joining (NHEJ) if unchecked. To avert DDR interference, Ad encodes several proteins in early region 4 (E4) that regulate the DDR to promote viral replication. Specifically, E4 11kDa and 34kDa have been shown to interact with DNA-dependent […]