St James's University Hospital
Wellcome Trust Brenner Building, room 6.14
Leeds LS9 7TF
Cancer metabolism; apoptosis; signalling pathways; mitogen-activated protein kinase (MAPK); c-Jun N-terminal kinase (JNK); NF-kappa B transcription factor.
- My current research programs focus on understanding basic cellular mechanisms (i.e. DNA transcription and protein post translational modifications), molecules that control complex regulatory pathways (signal transduction, gene regulation, development and differentiation), and the molecular basis for immunity, inflammation and cancer.
- The serine/threonine c-Jun-N-terminal kinase (JNK) is an important signalling pathway in eukaryotic cells, and has been chosen as model system to investigate the mechanisms of signal transduction.
- JNK responds to a variety of extracellular stimuli and regulates various cellular events, including the induction of apoptosis induced by reactive oxygen species (ROS), cell proliferation, and resistance to apoptosis.
- Consistent with the importance of these events in inflammation and tumorigenesis, regulation of JNK signalling is associated with immunity and cancers in humans.
- JNK1 and JNK2 are the major forms of JNK expressed ubiquitously.
- The paradigm is that both JNK1 and JNK2 contribute at the same cellular function.
- However, emerging evidence from our and other studies demonstrate that JNK1 and JNK2 have either distinct or even opposing biological functions, especially in cancer development (Barbarulo et al., Oncogene 2013; Bubici and Papa, Br J Pharmacol 2014).
- In a recent study published in Nature Communications (Iansante et al., Nat Commun 2015) we demonstrated that cancer cells stimulate the over-production of the protein known as PARP14, which enable cancer cells to use glucose to turbocharge their growth and override the natural check of cell death.
- Using a combination of genetic and molecular biology approaches, we have also uncovered an intricate link between JNK and cellular metabolism, providing evidence for JNK regulating an inextricable crosstalk between apoptosis and metabolism (Papa S, Bubici C, Mol Cell Oncol 2016)