Alfonso Martínez de la Cruz
Alfonso Martínez de la Cruz
Liver Disease Lab
Address: Bizkaia Science and Technology Park, building 801A, Derio (Bizkaia)

Alfonso Martínez de la Cruz got his undergraduate degree in Chemistry from the Universidad Autónoma de Madrid, Spain (1992). He finished his PhD work at the Department of Crystallography of Institute Rocasolano (1997) under a FPI fellowship from the Spanish Ministry of Science. Afterwards, he held three post doctoral positions, first at the Max Planck Institute Für Medizinische Forschung in Heidelberg, Germany in the lab of Professors Ken Holmes and Wolfgang Kabsch, where he carried out structural studies of proteins involved in Chagas disease (March-October, 1997). His work there was done in collaboration with Prof. Luise Krauth-Siegel, at the Department of Biochemistry of the University of Heidelberg. In October 1997 he moved to USA to join Sung-Hou Kim´s lab at Univ. of California, Berkeley, granted by a Fulbright Fellowship and later by a postdoctoral contract at the Department of Chemistry of this University. His work at Berkeley focused on the nascent Structural Genomics Initiative, aimed to perform high-throughput structure determination of proteins to setup the limits of the protein fold universe. In September 2000, he returned to Spain and joined the lab of Prof. José María Mato at the Univ. of Navarra, in Pamplona, granted first by a postdoctoral fellowship and later under a contract as a Scientist at the Center for Applied Medical Research (CIMA). During his stay in Pamplona he performed structural studies on enzymes regulated by S-adenosylmethionine (AdoMet), a hub molecule of the methionine cycle, that regulates the activity of several metabolic enzymes linked to the development of human liver diseases, including liver cancer and several rare pathologies. The biological relevance and complex regulation of one of this enzymes, cystathionine beta-synthase (CBS), which is key in regulating the transsulfuration pathway in mammals, focused his attention for future studies. In January 2005, he joined CIC bioGUNE, in Bilbao, as Principal Investigator.

Latest Publications

















During 2015-2018 Liver Disease Lab (LDL) has published 35 peer reviewed articles, 18 of them in the first Decil (Nature Communicaton, Cell Metab, Nature, Hepatology, Gut, Gastroenterology etc) and  eleven of them  in the first quartile with an average impact factor of 9. We have been successful obtaining funding from different national and internationals agencies such as the Ministry of Economy Science and Competitiveness, Carlos III Health Institute, Foundations, crowdfunding and international projects derived from NIH. The visibility of our research group in the liver field has been intensified through an extensive participation in different national and international networks such as Ciberehd (Carlos III Health Institute), Women in Hepatology (International Consortium) and different European COST actions PROTEOSTASIS, TRANSAUTOPHAGY and MITOEAGLE.

Tutoring is an important factor in LDL and along these three years, nine PhD theses, 4 master's  and multiple undergraduate and technician students have been  trained. The co-direction of PhD students with different agencies like hospitals and technology centers has been of special relevance, contributing to enrich our research vision.

Regarding the research lines carried out in the LDL, we have generated three new areas of knowledge in this period of time, two of them practically unexplored, which have led us to be Cover Page of Hepatology in 2017 and to reach high impact journals such as Nature Communications, Gut or Cell Metabolism among others. These areas open new ways of knowledge in the liver field regarding metabolism, physiology and disease. These areas are a) post-translational modifications mainly NEDDylation b) Mitochondrial activity c) microRNAS and d) Magnesium metabolism.  In all of them, we have developed new biological tools, preclinical animal models and new therapeutic approaches that have ended in the generation of patents and the development of a robust translational research.

In fact, one of the relevant points during 2015 -2018 of LDL has been the transfer of our knowledge to biomedical and pharmaceuticals companies. We have generated three patents, all of them licensed and other two under development. Importantly, we have promoted the generation of Mitotherapeutix LLC (USA), a biopharmaceutical company that develops products for treatment of degenerative liver disorders, based on our R&D, with a first product in Phase I Clinical Trial and another molecule under development. We have also participated in the OWL Liver and OWL Test, the first test for non-invasive diagnose of NAFLD, currently commercialized.  We have actively collaborated with international companies such as Takeda Pharmaceutical and AGIOS in preclinical trials of their drugs and we have formal initiatives to transfer our R&D to important pharmaceutical companies. Regarding Basque Health cluster we have generated and consolidate initiatives with technological Engineers Centers (bioGUNE / TEKNIKER) with the aim to validate a candidate molecule as a predictive circulating marker of liver injury developing a promising low-cost effective Point-Of-Care technology to facilitate diagnosis and monitoring solutions in primary healthcare centers, pharmaceutical industry and for consumers
Therefore, in these three years we have generated knowledge, an extensive network of collaborations and we have proven preclinical models and transfer our R&D to national and international pharmaceutical companies.

Latest Publications

Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV-positive women with hepatocellular carcinoma

Critelli, RM;Milosa, F;Romanzi, A;Lasagni, S;Marcelli, G;Di Marco, L;Pivetti, A;Schepis, F;Romagnoli, D;Mancarella, S;Dituri, F;Martinez-Chantar, ML;Giannelli, G;Villa, E



ChemPert: mapping between chemical perturbation and transcriptional response for non-cancer cells

Zheng, ML;Okawa, S;Bravo, M;Chen, F;Martinez-Chantar, ML;Del Sol, A



The NADPH oxidase NOX4 regulates redox and metabolic homeostasis preventing HCC progression

Penuelas-Haro, I;Espinosa-Sotelo, R;Crosas-Molist, E;Herranz-Iturbide, M;Caballero-Diaz, D;Alay, A;Sole, X;Ramos, E;Serrano, T;Martinez-Chantar, ML;Knaus, UG;Cuezva, JM;Zorzano, A;Bertran, E;Fabregat, ...



Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression

Juarez-Fernandez, M;Goikoetxea-Usandizaga, N;Porras, D;Garcia-Mediavilla, MV;Bravo, M;Serrano-Macia, M;Simon, J;Delgado, TC;Lachiondo-Ortega, S;Martinez-Florez, S;Lorenzo, O;Rincon, M;Varela-Rey, ...



Endothelial angiopoietin-2 overexpression in explanted livers identifies subjects at higher risk of recurrence of hepatocellular carcinoma after liver transplantation

Lasagni, S;Leonardi, F;Pivetti, A;Di Marco, L;Ravaioli, F;Serenari, M;Gitto, S;Critelli, RM;Milosa, F;Romanzi, A;Mancarella, S;Dituri, F;Riefolo, M;Catellani, B;Magistri, P;Romagnoli, D;Celsa, ...



The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes

Mercado-Gomez, M;Prieto-Fernandez, E;Goikoetxea-Usandizaga, N;Vila-Vecilla, L;Azkargorta, M;Bravo, M;Serrano-Macia, M;Egia-Mendikute, L;Rodriguez-Agudo, R;Lachiondo-Ortega, S;Lee, SY;Gine, AE;Gil-Pitarch, ...



Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

Serrano-Macia, M;Lachiondo-Ortega, S;Iruzubieta, P;Goikoetxea-Usandizaga, N;Bosch, A;Egia-Mendikute, L;Jimenez-Lasheras, B;Azkargorta, M;Elortza, F;Martinez-Redondo, D;Castro, B;Lozano, JJ;Nogueiras, ...



Targeting cyclin M4 as a new therapeutical approach to treat alcoholic liver disease

Gonzalez-Recio, I;Goikoetxea, N;Agudo, RR;Espinosa, JS;Serrano-Macia, M;Azkargorta, M;Elortza, F;Diaz-Moreno, I;Diaz-Quintana, A;Schaeper, U;Bataller, R;Avila, MA;Martinez-Cruz, LA;Martinez-Chantar, ...



Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis

Fondevila, MF;Fernandez, U;Heras, V;Parracho, T;Gonzalez-Rellan, MJ;Novoa, E;Porteiro, B;Alonso, C;Mayo, R;Lima, ND;Iglesias, C;Filliol, AA;Senra, A;Delgado, TC;Woodhoo, A;Herrero, L;Serra, ...



Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors

Lachiondo-Ortega, S;Delgado, TC;Banos-Jaime, B;Velazquez-Cruz, A;Diaz-Moreno, I;Martinez-Chantar, ML