Anjali Gowripalan

Event Date: 
Tuesday, August 29, 2017 - 18:15 - 18:30
Institution: 
University of Sydney
Title: 

Honing the oncolytic weapon: Non-canonical Smad signalling during vaccinia virus infection

Abstract: 
Tumour cells possess many features which predispose them to viral infections, including an abundance of replication resources, a defective interferon response and localised evasion of host immune cells. Oncolytic viruses exploit these characteristics to preferentially replicate within tumour cells, multiplying rapidly and targeting cells for destruction by the host immune system. Vaccinia virus (VACV) is a well characterised oncolytic virus and has been studied extensively due to its role in the smallpox vaccine. To improve safety and specificity of its use in oncolytic therapy, numerous genetic modifications have been made, giving rise to a therapeutic strain known as JX-594. Unfortunately, there are still dangers associated with treatment, including the intratumoral route of administration, which dislodges malignant cells and encourages distal tumour formation. Recent work has focused on mining important elements of the VACV replication cycle to dig up novel targets to improve tumour selectivity. Observations made in our lab have demonstrated potent upregulation of TGF-β signalling upon VACV infection. These pathway components can be detected at both the transcript and protein level, via qPCR, immunoblot and immunofluorescence assays. Furthermore, using both CRISPR-Cas9 and siRNA technologies, we have demonstrated a novel role for Smad4, a transcription factor in this cascade, in a number of aspects of infection, including virus-induced cell invasion. As high levels of TGF-β signalling are associated with numerous tumours, including but not limited to colon, prostate, breast and hepatocellular carcinoma, understanding how VACV recruits this pathway could assist in shifting infection away from healthy cells and towards tumours.