SLMS Academic Careers Office

22.  Understanding the molecular mechanisms of pancreatic cancer progression

Supervisor Pair: Dr John Timms and Dr Stephen Pereira
Potential Student’s Home Department: Institute for Women’s Health, Women’s Cancer

Pancreatic cancer is a devastating disease that is most often diagnosed late, when curative therapies are no longer possible. New treatment strategies for advanced pancreatic cancer, as well as improved diagnostic and treatment options for precursor lesions and early pancreatic malignancies are urgently needed. Precursor lesions include intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and pancreatic intraepithelial neoplasms (PanINs). The mechanisms by which these precursor lesions progress to malignancy is poorly understood.

The aim of this project is to understand the molecular and cellular mechanisms that drive the oncogenic transformation of pancreatic cancer. Model cell lines will be developed from immortalised pancreatic ductal epithelial cells or precursor cell lines that overexpress frequently mutated oncogenic variants (KRas, GNAS) or reduced expression of tumour suppressor genes (p53, CDKN2A). The proliferation, survival and invasion of derived cell lines will be characterised using cell-based assays. Established proteomics-based profiling using in vivo metabolic labelling with SILAC will be used to examine global protein changes in response to oncogenic activation or tumour suppressor loss and these mapped to cellular phenotype to understand the molecular events associated with malignant progression. Commonly identified changes will be confirmed and promising candidates further tested in clinical and pre-clinical serum samples to establish their potential as biomarkers for the early detection of pancreatic cancer.

The project brings together expertise in cancer cell signalling and proteomics on UCL’s Bloomsbury campus with expertise in pancreatic cancer biology and diagnosis on the Royal Free campus. The two supervisors have a history of successful collaboration in the field of pancreaticobilliary disease, in particular, cancer biomarker discovery and validation. The partnerships will allow access to state of the art proteomics instrumentation, optimised proteomics workflows and established cancer cell biology techniques which will complement a substantial research programme in the area of pancreatic cancer detection and therapeutic intervention.