GASTROENTEROLOGY,

 HEPATOLOGY AND

 NUTRIGENOMICS

 

 

MEMBERS AND COLLABORATORS

 

Name

Category

E-mail

María Jesús Tuñón González (Coord)

CU Fisiología ULE

mjtung@unileon.es

Jose Luís Mauriz Gutierrez

TU Fisiología ULE

jl.mauriz@unileon.es

Beatriz San Miguel de Vega

PA Fisiología ULE

bsanv@unileon.es

Carolina Méndez Blanco Becario AECC cmenb@unileon.es
Flavia Fondevila Peña Becario FPU ffonp@unileon.es
Paula Fernández Palanca Becario FPU pferp@unileon.es

Irene Crespo Gómez

AD Fisiología Universidad de Oviedo

crespo@unilovi.es

Juan J. Ortiz de Urbina

Jefe del Servicio de Farmacia CAULE

jortiz@hleo.sacyl.es

Pedro Linares Torres Facultativo Especialista de Área, Servicio Aparato Digestivo CAULE pedrolinato@yahoo.es

Antonio Blanco Mercadé

Facultativo Especialista, Servicio Otorrinolaringología  CAULE

ablame@ono.com

Andrés García Palomo

Jefe del Servicio de Oncología  CAULE

agarciapaolomo@gmail.com

Santiago Vivas Alegre Facultativo Especialista de Área, Servicio Aparato Digestivo CAULE svivasa@gmail.com

Jesús M. Culebras Fernández

Investigador Colaborador

jm.culebras@telefonic.net

OBJECTIVES

 

1. To improve methods of prevention, diagnosis and treatment of human liver and gastrointestinal diseases through cellular and animal models

2. To test biological substances used in therapeutic analyzing the power, range and safety in these cellular and animal models.

3. Achieve the applicability/transference of basic research to the clinical setting

 

 

ACTIVITIES

 

The group is composed by researchers of different formation, including biologists, physicians, veterinarians and pharmacists, who come from the Department of Biomedical Sciences of the University of Leon and from different Units of the Hospital of León (Surgery, Pharmacy and Oncology). Our activity is related to the Inflamamation, oxidative stress and antioxidants Unit (led by Dr. González-Gallego at the same Institute of Biomedicine), and it has been shaped in the accomplishment of research projects funded by the Spanish National Plan of R+D, the Spanish Health Research Fund o the Regional Government of Castilla y León, and has made possible the development of research contracts with diverse multinational companies of the pharmaceutical sector.

 

Members of this group have been part of one of the nodes of a Cooperative Research Thematic Network of the Carlos III Health Institute on "Pathogenic mechanisms of viral hepatitis and steatohepatitis" (2003-2005). From its creation in 2006 they are members of the “Hepatic and Digestive Diseases “CIBER of the Spanish Health Ministry. Moreover, our unit collaborates with other groups such as the Center of Applied Medical Research (CIMA) at the University of Navarra (Spain), the Experimental Hepatology Unit at the Hospital La Fe (Spain), the Nanobiosensors and Bioanalytical Applications Group at CSIC (Spain), the Hepatology and Gastroenterology Laboratory of the Hospital of Porto Alegre and Federal University of Rio Grande do Sul (Brazil), the Department of Internal Medicine at the Johannes Gutenberg University (Germany), the Department of Chemistry at the Federal University of Santa Maria (Brazil), etc.

 

The group has centered its activity in the use of cellular and animal models for the study of pathophysiological and therapeutic aspects of liver and gastrointestinal diseases, with special interest on oxidative and inflammatory mechanisms as well as proliferation and cell death, and analyzing the potential effects of different molecules (drugs, nutraceutics, etc).

 

Interesting data have been obtained by our group using a new animal model of fulminant hepatic failure (FLF) through experimental rabbit infection with the rabbit hemorrhagic disease virus (RHDV). RHDV infection reproduces clinical, biochemical, and histological features of the human FLF syndrome and satisfies criteria for a suitable animal model. Additionally, we have demonstrated, in both animal and cellular models, that flavonoid administration could be useful against liver damage induced by diabetes, portal hypertension and other situations with oxidative stress or inflammation. Also, studies using animal models have confirmed the interest of glutamine derivatives as part of new parenteral formulations. Moreover, we have analyzed the beneficial effects of antioxidant molecules (such as melatonine) and new antiangiogenic drugs on human hepatocarcinoma treatment. Furthermore, we are studying the potential interest of new antioxidant molecules (such as diphenyl diselenide) blocking liver and neuronal acetaminophen-induced damage. Finally, we are developing new methods to analyze liver tumor markers like VEGF in blood samples using biosensors based on the surface plasmon resonance.

 

 

METHODOLOGY

 

STUDIES

  • Ex vivo e in vitro experimental models (isolated hepatocytes, liver and endotelial cell lines, ect)

  • In vivo experimental models (rat, rabbit, hamster, sheep, etc)

METHODS

  • Cell isolation

  • Human and animal cell culture

  • FACS and confocal microscopy

  • Blood biochemical markers

  • Coagulation

  • Histopathological and immunohistochemistry studies

  • Radiological studies (CHO, CT, NMR)

  • Intracraneal pressure monitoring

  • Oxidative stress markers and antioxidant ability

  • Citoquines and growth factors determination

  • Oxidative stress, inflammation and cell damage mediators expression

  • Transcription factors activation

  • Apoptosis and autophagy markers

  • Cell cycle and cell proliferation markers

  • Mitochondrial damage measurement

  • Study of biomedical application of new biosensors

 

TECHNOLOGICAL OFFER

 

1. Development of animal and cellular models for the study of pathogenetic mechanisms and beneficial effects of drugs and nutrients in different pathologies

2. Clinical and basic research on gastrointestinal and liver diseases.

3. Advising and transfer of technology to  companies in the health sector

4. Training in laboratory techniques

 

SELECTED PUBLICATIONS

  • “Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis”. B. San Miguel, I. Crespo, D. I. Sánchez, B. González-Fernández, J. J. Ortiz, M. J. Tuñón y J. González-Gallego. Journal of Pineal Research: 59, 151-162, 2015.

  • “Sensitivity and resistance to sorafenib in hepatocellular carcinoma: the role of autophagy”. N. Prieto-Domínguez, R. Ordoñez, A. Fernández, A. García-Palomo, J. González-Gallego, J. L. Mauriz. Frontiers in Pharmacology: 7, 151, 2016.

  • “Melatonin-induced increase in sensitivity of human hepatocellular carcinoma cells to sorafenib is associated with ROS production and mitophagy”.  N. Prieto-Domínguez, R. Ordóñez, A. Fernández, C. Méndez-Blanco, A. Baulies, C. Garcia-Ruiz, J. C. Fernandez-Checa, J. L. Mauriz y J. González-Gallego. Journal of Pineal Research: 61, 396-407, 2016.

  • “Protective effect of protocatechuic acid on TNBS-induced colitis in mice is associated with modulation of the Sphk/S1P signaling pathway”. I. Crespo, B. San-Miguel, J. L.  Mauriz, J. J.  Ortiz de Urbina, M. Almar, M. J. Tuñón y J. González-Gallego. Nutrients:  9, E288, 2017.

  • “Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine-induced hepatocellular carcinoma”.D. I. Sánchez, B. González-Fernández, I. Crespo, B. San-Miguel, M. Álvarez, J. González-Gallego y M. J. Tuñón. Journal of Pineal Research: e12506, 2018.

  • "Stabilization of hypoxia-inducible factors and BNIP3 promoter methylationcontribute to acquired sorafenib resistance in hepatocellular carcinoma cells”. C. Méndez-Blanco, F. Fondevila, P. Fernández-Palanca, A. García-Palomo, J. van Pelt, C. Verslype, J. González-Gallego y J. L. Mauriz.Cancers: 11, 1984, 2019

     

CONTACT