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metabolites useful to monitor the response. Moreover, we want to clarify and

define the metabonomic patterns that will predict the success of a liver before

transplantation, to do this we analyze the metabonome of livers transplanted,
whose post-transplant performance is known.

• Liver Cell Therapy: the goal is to apply cell therapy (hepatocyte or mesenchy-

mal cells) for the treatment of certain liver diseases: acute liver failure, acute

decompensation in chronic liver disease, primary biliary cirrhosis and congenital
metabolic disorders, thus making it a therapeutic strategy that can be applied

as a bridge or as an alternative to whole organ transplantation.

• s F, C CF, B M, t J, C Jv, B r. Gata4 blocks somatic cell
Most relevant erraNoaLatayuDLazQuezorresasteLLort
reprogramming by directly repressing Nanog.Stem Cells. 2013 Jan;31(1):71-82.
scientific • g C, B M, p-v s, M M, g-M Mv, M-C ML.
uzMáNeNetisoNeroaQuerooyaarCíaeDiaviLLaartíNezhaNtar
articles
The human liver fatty acid binding protein (FABP1) gene is activated by FOXA1 and PPARα;
and repressed by C/EBPα: Implications in FABP1 down-regulation in nonalcoholic fatty liver

disease.Biochim Biophys Acta. 2013 Apr;1831(4):803-18.
• ó
CarBaJo-pesCaDor s, orDoñez r, BeNet M, Jover r, garCía-paLoMo a, Mauriz JL. Inhibition of VEGF
expression through blockade of Hif1α and STAT3 signalling mediates the anti-angiogenic
effect of melatonin in HepG2 liver cancer cells.Br J Cancer. 2013 Jul 9;109(1):83-91.

• toLosa L, gMez-LeChóN MJ, pérez-CataLDo g, CasteLL Jv, DoNato Mt. HepG2 cells simulta-

neously expressing five P450 enzymes for the screening of hepatotoxicity: identification
of bioactivable drugs and the potential mechanism of toxicity involved.Arch Toxicol. 2013
Jun;87(6):1115-27.

• BLazQuez M, Carretero a, eLLis JK, athersuCh tJ, CaviLL r, eBBeLs tM. A combination of transcrip-

tomics and metabolomics uncovers enhanced bile acid biosynthesis in HepG2 cells expres-
sing CCAAT/enhancer-binding protein β (C/EBPβ), hepatocyte nuclear factor 4α (HNF4α),
and constitutive androstane receptor (CAR).J Proteome Res. 2013 Jun 7;12(6):2732-41.

In late 2013 we finished two research projects funded by the Institute of Health Carlos
Highlights
III (ISCIII). The purpose of one of the projects has been the citomic and metabonomic
study of the hepatotoxic mechanism of drugs, the prediction of their hepatotoxic poten-

tial and the transition from iatrogenic to autoimmune hepatitis. This project has achieved
the development and validation of a practical and reproducible multiparametric method

for evaluating and predicting drugs that are potentially hepatotoxic to humans. The other

project has focused on the study of novel transcriptional mechanisms involved in the
pathogenesis of nonalcoholic fatty liver disease of both metabolic and iatrogenic etiology.

One of the most significant results has been the finding of a transcriptomic fingerprint
able to identify new steatotic drugs.

Projects are underway in 2013 include:

• Study of the Hex-mediated activity of MYC in cell reprogramming (Ministry of Science 13
and Innovation, 2012-2014)
20
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• Finding a metabonomic pattern for fast pre-implantation assessment of the functional OR
P
quality of the donor liver graft (ISCIII, 2012-2014).
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• Innovative strategies to generate human hepatocytes for treatment of metabolic liver A
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diseases: Tools for personalised cell therapy (InnovaLiv EU, 2011-2014).
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A
Finally, among the projects beginning in 2013 is worth to mention a project funded by D /
the European Union, from 2013 to 2017, and entitled “HeCaToS - Hepatic and Cardiac H
E
Toxicity Systems modelling”. For this project, a new Hepatotoxicity Unit service has re- ER
cently been founded in Hospital La Fe, as a result of the synergy between our Unit and IB
C
the Clinical Hepatology Unit (HU), to which patients with suspected drug hepatotoxicity
are referred for a detailed and personalized study.
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