Dr Salvatore Papa

Dr Salvatore Papa

University Academic Fellow, Head of Cell signaling and Cancer Group

+44-113-343-9038

Summary: Dr Salvatore Papa gained a first class in Molecular Biology followed by a PhD in Experimental Medicine.

Location: Wellcome Trust Brenner building, Level 6.

Teaching Commitments: Current PhD student: Nathan Lee, LICAP PhD Student, University of Leeds. Supervision Topics: Cancer metabolism; apoptosis; signalling pathways; mitogen-activated protein kinase (MAPK); c-Jun N-terminal kinase (JNK); NF-kappa B transcription factor.

Overview

My graduate studies were carried out in the Ben May Department for Cancer Research at University of Chicago, USA. I completed my postdoctoral training at Imperial College London, where I became interested in experimental haematology and oncology. After promotion to Senior Research Fellow (Lecturer status) in 2009 sponsored by a Wellcome Trust personal award, I began my independent career as Group Leader at the Institute of Hepatology London sponsored by UK charities (i.e. the Foundation for Liver Research and AMMF-the cholangiocarcinoma charity). Current research efforts in Dr Papa’s laboratory are aimed to the identification and characterization of novel anti-apoptotic factors as potential cancer biomarkers.

During my postgraduate studies, my efforts have been directed towards the identification and characterization of the downstream effectors of the prosurvival activity of NF-kappaB.  My primary focus was to uncover a mechanism by which Gadd45b, a downstream effector of NF-kappaB, blunts JNK signalling. We have identified the MAPKK MKK7/JNKK2 – a specific and essential activator of JNK – as a target of Gadd45b, and in fact, of NF-kappaB itself. Gadd45b associates directly and tightly with MKK7, inhibiting its catalytic activity, and this inhibition is central to the Gadd45b-mediated suppression of TNF-induced JNK signalling and apoptosis (Papa S. et al., Nat Cell Biol 2004; Papa S. et al., J Biol Chem 2007; Papa S. et al., J Clin Invest 2008; Papa S. et al., Biol Chem 2009).

After completing my research training at University of Chicago and Imperial College London, I was appointed Group Leader at the Institute of Hepatology London, establishing my independent group while continuing my honorary association with the Department of Surgery & Cancer at Imperial College London. Starting May 2016, I have joined the Leeds Institute of Cancer and Pathology (LICAP) at University of Leeds to lead the Cell Signaling and Cancer group.

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) (see schematic Figure). A full coverage of our recent study has been discussed at The Conversation UK and can be found at: https://theconversation.com/starving-cancer-cells-of-sugar-could-be-the-key-to-future-treatment-47906