Rushika M. Perera, PhD

Organelle dynamics and metabolic reprogramming in pancreatic cancer

How do cancer cells escape tightly controlled regulatory circuits that link their growth to extracellular signaling cues? An emerging theme in cancer biology is how, in addition to genetic alterations in signaling pathways (eg. MAPK and PI3K), cancer cells can hijack normal stress response pathways to overcome strict reliance on external nutrients for growth. Pancreatic adenocarcinoma (PDA) is the quintessence of an aggressive malignancy that thrives in nutrient poor, hypoxic environments, by systematically altering the core pathways for nutrient acquisition and utilization. These alterations include increased uptake of glucose and glutamine, along with constitutive activation of scavenging pathways that converge at the lysosome, namely autophagy (cellular self-catabolism) and macropinocytosis (bulk uptake of extracellular material).

In our lab we study the cancer-specific mechanisms of autophagy-lysosome activation, and how this organellar system contributes to metabolic reprogramming in PDA. We hypothesize that the functional interplay between enhanced cellular trafficking pathways and activation of gene programs that regulate organelle dynamics and function is an essential, previously unrecognized mechanism for tumor growth. Our studies using a combination of biochemistry, fluorescence imaging and proteomics in PDA cell lines, mouse models and primary patient derived cultures aims to provide insight into how fundamental cellular process are rewired in cancer while also identifying new nodes for anti-cancer therapy.