Project 466881

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest types of cancer, with only 8% of patients surviving beyond five years. The poor prognosis of patients with PDAC highlights a need to better understand this cancer and its subtypes. In general, the PDAC subtypes lie on a spectrum, with the ;Classical subtype on one end and the ;Basal-like subtype on the other. PDAC tumours are classified into subtypes by their gene expression, such as the GATA6 gene which is more highly expressed in Classical tumours than in Basal-like tumours. Our lab has recently found that by knocking out GATA6 in Classical tumours, tumour growth is reduced. This suggests that GATA6 is an important gene in tumour proliferation. On the contrary, other studies have shown a tumour suppressive role for GATA6. Therefore, my goal is to delineate the role of GATA6 in PDAC subtypes. I hypothesize that the role of GATA6 is context-dependent, and that it acts as a tumour suppressor in Basal-like tumours as opposed to its tumour-promoting role in Classical tumours. To test this hypothesis, I will first generate 3D cell models (organoids) that overexpress GATA6. The GATA6-overexpressing organoids will also express green fluorescent protein, enabling me to track their growth over time using flow cytometry. To investigate the molecular function of GATA6, I will perform RNA sequencing which will identify changes in gene expression that result from GATA6 overexpression. Finally, I will explore the protein-protein interactions of GATA6 to find potential targets for new therapies. Overall, by understanding the role of GATA6 in different PDAC subtypes, this project seeks to identify more personalized treatment options and improve the prognosis for patients with this deadly disease.