Imperial College London

Dr Salvatore Papa

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 3313 8282s.papa

 
 
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Location

 

10N.13Commonwealth BuildingHammersmith Campus

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Summary

 

Summary

My Lab Website

Google Scholar

During the past few years, 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 Gadd45β, 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 Gadd45{beta}, and in fact, of NF-kappaB itself. Gadd45{beta} 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). Subsequently, we have defined the precise mechanism by whichGadd45{beta} blocks MKK7, and ultimately, TNF-induced programmed cell death (Papa S. et al., J Biol Chem, 2007). These findings identify the MKK7-Gadd45{beta} interaction as a potential new target for anti-inflammatory and anti-cancer therapy. Interestingly, pharmacological compounds that disrupt Gadd45{beta} binding to MKK7 might uncouple anti-apoptotic and proinflammatory functions of NF-kappaB, and so, circumvent the potent immunosuppressive side effects of global blockers of NF-kappaB.  

To understand the physiological contexts in which Gadd45{beta} blocks the JNK activity, I then generated and analyzed Gadd45{beta}-null mice. Analyses of these mice revealed that Gadd45{beta} is required for liver regeneration, and the regenerative response is associated with selective attenuation of JNK2 isoform. These findings have important implications for treatment of widespread liver diseases (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've been appointed at the Institute of Hepatology London as Group Leader while continuing to teach and supervise MSc and BSc students at Imperial College.

Since 2016, I have joined the Leeds Institute of Medical Research  at University of Leeds to lead the Cell Signaling and Cancer group. The focus of our research is to understand the molecular mechanisms, regulation and role of apoptosis (i.e. programmed cell death) in the pathogenesis of human conditions, and translating these insights in therapeutic concepts and novel treatments for diseases including cancer, inflammation and infectious disease.

Fo more updated informations visit my lab website

Selected Publications

Journal Articles

Bubici C, Lepore A, Papa S, 2019, ASKing no more: the emerging role of DUSP12 in the regulation of hepatic lipid metabolism, Hepatology, ISSN:0270-9139

Bubici C, Papa S, 2019, Editorial: The warburg effect regulation under siege: the intertwined pathways in health and disease, Frontiers in Cell and Developmental Biology, Vol:7, ISSN:2296-634X

Papa S, Choy PM, Bubici C, 2019, The ERK and JNK pathways in the regulation of metabolic reprogramming, Oncogene, Vol:38, ISSN:0950-9232, Pages:2223-2240

Lee NCW, Carella MA, Papa S, et al., 2018, High expression of glycolytic genes in cirrhosis correlates with the risk of developing liver cancer, Frontiers in Cell and Developmental Biology, Vol:6, ISSN:2296-634X

Papa S, Bubici C, 2018, Feeding the hedgehog: a new meaning for JNK signalling in liver regeneration, Journal of Hepatology, Vol:69, ISSN:0168-8278, Pages:572-574

Manka P, Coombes JD, Boosman R, et al., 2018, Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment, Cancer Letters, Vol:419, ISSN:0304-3835, Pages:175-186

Verzella D, Bennett J, Fischietti M, et al., 2017, GADD45β loss ablates innate immunosuppression in cancer, Cancer Research, Vol:78, ISSN:1538-7445, Pages:1275-1292

Papa S, Bubici C, 2016, Linking apoptosis to cancer metabolism: Another missing piece of JuNK, Molecular & Cellular Oncology, Vol:3, ISSN:2372-3556

Iansante V, Choy PM, Fung SW, et al., 2015, PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation, Nature Communications, Vol:6, ISSN:2041-1723

Coombes JD, Swiderska-Syn M, Dolle L, et al., 2015, Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice, Gut, Vol:64, ISSN:0017-5749, Pages:1120-1131

Bubici C, Papa S, 2014, JNK signalling in cancer: in need of new, smarter therapeutic targets, British Journal of Pharmacology, Vol:171, ISSN:0007-1188, Pages:24-37

Barbarulo A, Iansante V, Chaidos A, et al., 2013, Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma, Oncogene, Vol:32, ISSN:0950-9232, Pages:4231-4242

Svensson CI, Inoue T, Hammaker D, et al., 2009, Gadd45 beta Deficiency in Rheumatoid Arthritis Enhanced Synovitis Through JNK Signaling, Arthritis and Rheumatism, Vol:60, ISSN:0004-3591, Pages:3229-3240

Papa S, Bubici C, Zazzeroni F, et al., 2009, Mechanisms of liver disease: the crosstalk between the NF-kappaB and JNK pathways., Biol Chem, Vol:390, Pages:965-976

Papa S, Zazzeroni F, Fu YX, et al., 2008, Gadd45{beta} promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling, J Clin Invest, Vol:118, Pages:1911-1923

Pham CG, Bubici C, Zazzeroni F, et al., 2007, Upregulation of Twist-1 by NF-kB blocks cytotoxicity induced by chemotherapeutic drugs, Mol Cell Biol, Vol:27, Pages:3920-3935

Papa S, Monti SM, Vitale RM, et al., 2007, Insights into the structural basis of the Gadd45ß mediated inactivation of the JNK kinase, MKK7, J Chem Biol, Vol:282, Pages:19029-19041

Bubici C, Papa S, Dean K, et al., 2006, Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance, Oncogene, Vol:25, ISSN:0950-9232, Pages:6731-6748

Papa S, Bubici C, Zazzeroni F, et al., 2006, The NF-kappa B-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease, Cell Death and Differentiation, Vol:13, ISSN:1350-9047, Pages:712-729

Pham CG, Bubici C, Zazzeroni F, et al., 2004, Ferritin heavy chain upregulation by NF-kappa B inhibits TNF alpha-induced apoptosis by suppressing reactive oxygen species, Cell, Vol:119, ISSN:0092-8674, Pages:529-542

Papa S, Zazzeroni F, Pham CG, et al., 2004, Linking JNK signaling to NF-kappa B: a key to survival, Journal of Cell Science, Vol:117, ISSN:0021-9533, Pages:5197-5208

Papa S, Zazzeroni F, Bubici C, et al., 2004, Gadd45{beta} mediates the NF-kappaB suppression of JNK signalling by targeting MKK7/JNKK2., Nat. Cell Biol., Vol:6, Pages:146-153

Zazzeroni F, Papa S, De Smaele E, et al., 2003, Cell signalling (communication arising) - Cell survival and a Gadd45-factor deficiency - Reply, Nature, Vol:424, ISSN:0028-0836, Pages:742-742

De Smaele E, Zazzeroni F, Papa S, et al., 2001, Induction of gadd45 beta by NF-kappa B downregulates pro-apoptotic JNK signalling, Nature, Vol:414, ISSN:0028-0836, Pages:308-313

Conference

Iansante V, Zen Y, Barbarulo A, et al., 2012, MAPK SIGNALLING REGULATES THE DEVELOPMENT OF A CHOLANGIOCELLULAR PHENOTYPE FROM HCC IN POST-TACE LIVER TRANSPLANTS, 1st Combined Digestive Disorders Federation Meeting of the British-Society-of-Gastroenterology (BSG), Association-of-Upper-Gastrointestinal-Surgeons (AUGIS), BAPEN and British-Association-for-the-Study-of-the-Liver (BASL), BMJ PUBLISHING GROUP, Pages:A416-A416, ISSN:0017-5749

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