Molecular MedicineMetabolic engineering and diabetes therapy

Metabolic engineering and diabetes therapy
Group Leader

Professor (Biochemistry and Molecular Biology Dept. - UB)

+34 93 40 37111

The group directed by Prof. Guinovart is involved in several projects on glycogen metabolism and its dysfunctions in diabetes and Lafora disease. Studies on glycogen metabolism have allowed the identification of many enzymes and intermediate metabolites involved in the synthesis and degradation of this polysaccharide. However, new factors and processes that participate in glycogen regulation are constantly being discovered. Moreover, data on the mechanisms of control in distinct organs and in diverse physiological conditions are incomplete. The alteration of one of these mechanisms may lead to serious pathologies such as diabetes mellitus and Lafora disease. The discovery of compounds that counteract the alterations of glucose metabolism is of potential interest for the treatment of diabetes mellitus.

  • To study the mechanisms of glucose storage in the form of glycogen in liver, muscle and brain and its alterations in diabetes and neurological disorders.
  • To identify and characterize novel compounds with anti-diabetic action.
  • To identify novel potential molecular targets for the design of anti-diabetic compounds.

1) Regulation of hepatic, muscular and neuronal glycogen metabolism. Alterations in pathological conditions: diabetes mellitus and Lafora disease.

Main tasks:
a) Identification and functional analysis of the phosphorylation sites in the liver isoform of glycogen synthase.
b) Identification of the regulatory domains of glycogen synthases through structural and phylogenetic analyses.
c) Analysis of the physiological significance of the translocation of the muscle and liver isoenzymes of glycogen synthase.
d) Characterization of glycogen synthesis in neurons. Study of the components of the glycogen synthesis and degradation pathways in this cellular type.
e) Study of the alterations in glycogen metabolism in pathological situations.

  • Analysis of alterations in the post-translational modification pattern or in the subcellular localization of glycogen synthase in diabetes mellitus.
  • Study of the alterations in neuronal glycogen metabolism that lead to the production of polyglucosan bodies in Lafora disease. Involvement of laforin and malin.

2) Study of anti-diabetic agents and their possible application in diabetes treatment.

Main tasks:

  • Identification of the molecular targets of the anti-diabetic agent sodium tungstate.
  • Identification of new molecular targets for the design of anti-diabetic agents.
Slebe F, Rojo F, Vinaixa M, García-Rocha M, Testoni G, Guiu M, Planet E, Samino S, Arenas EJ, Beltran A, Rovira A, Lluch A, Salvatella X, Yanes O, Albanell J, Guinovart JJ and Gomis RR.
Nat Commun, 7 11199 (2016)
López-Ramos JC, Duran J, Gruart A, Guinovart JJ and Delgado-García JM.
Front Cell Neurosci, 9 431 (2015)
Duran J and Guinovart JJ.
Mol Aspects Med, 46 70-7 (2015)
López-Soldado I, Zafra D, Duran J, Adrover A, Calbó J and Guinovart JJ.
Diabetes, 64 (3), 796-807 (2015)
Zeqiraj E, Tang X, Hunter RW, García-Rocha M, Judd A, Deak M, von Wilamowitz-Moellendorff A, Kurinov I, Guinovart JJ, Tyers M, Sakamoto K and Sicheri F.
P Natl Acad Sci Usa, 111 (28), E2831-40 (2014)
Sinadinos C, Valles-Ortega J, Boulan L, Solsona E, Tevy MF, Marquez M, Duran J, Lopez-Iglesias C, Calbó J, Blasco E, Pumarola M, Milán M* and Guinovart JJ*
Aging Cell, 13 (5), 935-945 (2014)
Saez I, Duran J, Sinadinos C, Beltran A, Yanes O, Tevy MF, Martínez-Pons C, Milán M and Guinovart JJ.
J Cerebr Blood F Met, 34 (6), 945-55 (2014)
Duran J, Gruart A, García-Rocha M, Delgado-García JM and Guinovart JJ.
Hum Mol Genet, 23 (12), 3147-56 (2014)
Duran J, Saez I, Gruart A, Guinovart JJ and Delgado-García JM.
J Cerebr Blood F Met, 33 (4), 550-6 (2013)
Díaz A, Díaz-Lobo M, Grados E, Guinovart JJ, Fita I and Ferrer JC.
Iubmb Life, 64 (7), 649-58 (2012)
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M* and Guinovart JJ*.
EMBO Mol Med, 4 (8), 719-29 (2012)
Díaz A, Martínez-Pons C, Fita I, Ferrer JC and Guinovart JJ.
J Biol Chem, 286 (21), 18505-14 (2011)
Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, Serafin A, Cañas X, Soriano E, Delgado-García JM, Gruart A and Guinovart JJ.
EMBO Mol Med, 3 (11), 667-81 (2011)
Cifuentes D, Martínez-Pons C, García-Rocha M, Galina A, Ribas de Pouplana L and Guinovart JJ.
J Biol Chem, 283 (9), 5642-9 (2008)
Vilchez D, Ros S, Cifuentes D, Pujadas Ll, Vallès J, García-Fojeda B, Criado-García O, Fernández-Sánchez E, Medraño MI, Domínguez J, García Rocha M, Soriano E, Rodríguez de Córdoba S and Guinovart JJ
Nat Neurosci, 10 (11), 1407-13 (2007)

* shared senior authorship

This group receives financial support from the following sources:

  • Instituto de Salud Carlos III. Ministerio de Sanidad y Consumo (Spanish National Institute of Health)
  • Fundació “La Caixa” ("la Caixa" Foundation)
  • Ministerio de Educación y Ciencia (Spanish Ministry of Education and Science)
  • Fundación Marcelino Botín (M. Botín Foundation)
  • Marató de TV3
  • Ministerio de Economía y Competitividad (MINECO)
  • European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"

     

Group news & mentions

20 Apr 2016

The newspaper published in Lleida devotes an article to the recent finding made by the researchers Felipe Slebe, Joan Guinovart and Roger Gomis in breast cancer.

18 Apr 2016

In an extensive interview on Radio Nacional de España, Radio Exterior, Felipe Slebe explains the breakthroughs in the fight against cancer made at IRB Barcelona.

Upcoming events

26 Sep
Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Emil Pai, University of Toronto
30 Sep
Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Sir Philip Cohen, Ph.D. MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences. University of Dundee. Scotland (UK)
03 Oct - 05 Oct
Institut d'Estudis Catalans (IEC), Barcelona