Malu Martínez-Chantar
mlmartinez
Malu Martínez-Chantar
PRINCIPAL INVESTIGATOR

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

Address: Bizkaia Science and Technology Park,
building 800, 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.

Non-alcoholic fatty liver disease (NAFLD) is a clinicalpathological term that includes a spectrum of alterations ranging from the simple accumulation of triglycerides in the hepatocytes (steatosis) to steatosis with hepatic inflammation (steatohepatitis or NASH). NASH, in turn, also progresses to cirrhosis and HCC. The mechanisms that lead to the expression of NASH are not clear, but it is a condition associated with obesity, insulin resistance, and diabetes. Since the incidence of these diseases is increasing, the prevalence of NASH is also expected to increase in coming years (today it varies between 13 to 15 % of the population). NASH is now considered to be an emerging disease in USA and occidental countries.Nowadays, lacking accurate, sensitive diagnostic test, distinguishing steatosis from steatohepatitis requires the use of invasive techniques like liver biopsy. To summarize, the lack of information about the factors implicated in the NASH pathogenesis, as well as in the prognostics characteristics and the treatment of this pathology, highlights the need of new approach in order to understand the mechanisms involved in the development of NASH and the progression to cirrhosis and liver cancer. Over the last few years, we have elucidated new molecular mechanisms implicated in the proliferation, regeneration and apoptosis and identified targets that contributing to the abnormal hepatic lipid metabolism and proliferation ended in the development of cirrhosis and liver cancer.The most important projects ongoing in my laboratory are focused on the role of posttranslational modifications throughout different stages of liver disease and ranges from effects on whole organ, such as NEDD8 inhibition on development of fibrosis, to more molecular approaches such as autophagy in hepatic steatosis and the role of LKB1 in hepatocellular carcinoma. In this respect, Metabolism has been one of the most important goals as well as  the mitochondria function in liver disease. Finally we have maintained a closed collaboration with the company OWL Metabolomics in the development of OWLiver® Care and OWLiver®, two non-invasive assays for fatty liver screening and for NASH diagnosis and Millennium Pharmaceuticals and Mitotherapeutix for the discovery of new drugs for the treatment of cirrhosis-NAFLD dependent and Liver Cancer.