Genetic diseases of connective tissue: Williams syndrome. PI: Victoria Campuzano Uceda

Presentation

Williams-Beuren syndrome (WBS) [OMIM 194050] is a neurodevelopmental disorder caused by the heterozygous deletion of 26-28 contiguous genes on chromosome 7q11.23 that affects 1/7500-1/20000 newborns. WBS individuals present mild to moderate intellectual disability, with a mean intelligence quotient (IQ) of 55-60. The syndrome is characterized by a unique cognitive functioning including relatively preserved expressive language and facial processing abilities along with hypersociability towards strangers but dramatic deficits in spatial cognition. Mainly due to Elastin (ELN) deficiency, WBS patients show a generalized arteriopathy characterized by hypertrophy of smooth muscle cells, increased number and disorganized lamellar structures, and fragmented elastic fibers. The complete deletion (CD) mouse model captures several behavioral and cardiovascular defects that are seen in humans with WBS.


Victoria Campuzano Uceda
Assistant professor
Serra-Hunter Program

vcampuzanou@ub.edu

 


Noura Abdalla
PhD student
nabdalla89@ub.edu

  • Identification of molecular biomarkers: Analyze mitochondrial function in tissues (and cells derived from them) mainly affected in the CD mouse model (cardiac and neural).
  • Identification of the major player in mitochondria dysfunction: genetic rescue of DNAJC30 gene expression in cell cultures derived from the CD model.
  • Analysis of a possible depressive behaviour: Behavioral characterization of CD mouse model in relationship with the depressive phenotype.
  • Identification of “in vivo” cardiovascular biomarquers: Electrocardiogram to CD animals
  • Genetic rescue by means of Adeno-associates of the expression of the DNAJC30 gene
  • Pharmacological intervention: combining anti-hypertensives and mitochondria-targeted therapies

  • Recuperación Genética y Farmacológica del déficit en la cognición, la interacción social y la ansiedad a través de eficiència funcional de GTF2I

MINECO (SAF2016-78508-R)
(04/06/2019 – 31/12/2020)
PI: Victoria Campuzano

  • Studying the mitochondrial health of cardiomyocytes and vascular smooth muscle cells in Williams Syndrome

Fundation Autour des Williams (France)
(2019-2020)
PI: Victoria Campuzano

  • Molecular bases in the effectiveness of the treatment of Williams-Beuren syndrome by inhibitors of the monoacyl glycerol lipase

Fondation Jerome Lejeune
(2018-2019)
PI: Victoria Campuzano

  • Genetic and pharmacological recovery of cognition deficit, social interaction and anxiety through GTF2I functional efficiency

Ministerio de Economía y Competitividad (MCINN)
(2017-2019)
OI: Victoria Campuzano

  • Modulación de la Expresión de GTF2I: Correlación entre Fenotipo Cognitivo, Morfologia Neural y Alteración Molecular (Ref: SAF2012-40036)

Ministerio de Economía y Competitividad (MCINN)
(2013-2015)

PI: Victoria Campuzano

For more information for PI publications click in the links:
WoS Researcher ID: G-1826-2014
SCOPUS Author ID: 6602504477

ORCID: 0000-0001-8128-2641

 

Rodríguez-Rovira I, López-Sainz A, Palomo-Buitrago ME, Pérez B, Jiménez-Altayó F, Campuzano V, Egea G. Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome. Int J Mol Sci. 2023 Jul 10; 24(14): 11293. doi: 10.3390/ ijms241411293. PMID: 37511051

Abdalla N, Tobías-Baraja E, Gonzalez A, Garrabou G, Egea G, Campuzano V. Dysfunctional Mitochondria in the Cardiac Fibers of a Williams-Beuren Syndrome Mouse Model. Int J Mol Sci. 2023 Jun 13; 24(12): 10071. doi: 10.3390/ ijms241210071. PMID: 37373217

Abdalla N, Ortiz-Romero P, Rodriguez-Rovira I, Pérez-Jurado LA, Egea G, Campuzano V. The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams-Beuren Syndrome Mouse Model. Int J Mol Sci. 2023 Feb 7; 24(4): 3261. doi: 10.3390/ ijms24043261. PMID: 36834670

Giannoccaro S, Ferraguto C, Petroni V, Marcelly C, Nogues X, Campuzano V, Pietropaolo S. Early Neurobehavioral Characterization of the CD Mouse Model of Williams-Beuren Syndrome. Cells. 2023 Jan 21; 12(3): 391. doi: 10.3390/cells12030391. PMID: 36766733

Kühne BA, Teixidó E, Ettcheto M, Puig T, Planas M, Feliu L, Pla L, Campuzano V, Gratacós E, Fritsche E, Illa M, Barenys M. Application of the adverse outcome pathway to identify molecular changes in prenatal brain programming induced by IUGR: Discoveries after EGCG exposure. Food Chem Toxicol. 2022 Dec;170: 113506. doi: 10.1016/ j.fct.2022.113506. Epub 2022 Nov 10. PMID: 36370916

Rodríguez-Rovira, I.;De Rycke, K.; Arce, C.; Pérez, B.; Carretero, A.; Arbonés, M.; Teixidò-Turà, G.; Gómez-Cabrera, M.C.; Campuzano, V.; Jiménez-Altayó, F.; Egea, G. Allopurinol Blocks The Formation And Progression Of Aortic Aneurysm In A Mouse Model Of Marfan Syndrome. BioRxiv Preprint January 16, 2022. doi.org/ 10.1101/ 2021.10.13.464182.

Navarro-Romero, A.; Galera-López, L.; Ortiz-Romero, P.; Llorente-Ovejero, A.; de los Reyes-Ramírez, L.; Mas-Stachurska, A.; Reixachs-Solé, M.; Pastor, A.; de la Torre, R.; Maldonado, R.; Benito, B.; Eyras, E.; Rodríguez-Puertas, R.; Campuzano, V.; Ozaita, A. Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome. BioRxiv Preprint August 19, 2021. doi.org/ 10.1101/2021.08. 16.456474.

Arce, C.; Rodríguez-Rovira, I.; De Rycke, K.; Durán, K.; Campuzano, V.; Fabregat, I; Jiménez-Altayó, F.; Berraondo, P.; Egea, G. Anti-TGFβ (Transforming Growth Factor β) Therapy with Betaglycan-derived P144 peptide gene delivery prevents the formation of Aortic Aneurysm in a mouse model of Marfan Syndrome. Arterioscler Thromb Vasc Biol. 2021 Sep; 41(9): e440-e452. doi: 10.1161/ ATVBAHA. 121.316496. Epub 2021 Jun 24. Pmid: 34162229

Ortiz-Romero, P; González-Simón, A; Egea, G; Pérez-Jurado, LA; Campuzano, V.  Co-Treatment With Verapamil and Curcumin Attenuates the Behavioral Alterations Observed in Williams-Beuren Syndrome Mice by Regulation of MAPK Pathway and Microglia Overexpression. Front Pharmacol. 2021 Aug 3;12: 670785. doi: 10.3389/ fphar. 2021. 670785. eCollection 2021.  PMID: 34413771

Egea G; Jiménez-Altayó F; Campuzano V. Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue. Antioxidants (Basel) 2020 Oct 19;9(10):1013. doi: 10.3390/ antiox 9101013. PMID: 33086603

Jiménez-Altayó F; Ortiz-Romero P; Puertas-Umbert L; Dantas AP: Pérez B; Vila E; D'Ocon P; Campuzano V. Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome. Sci Rep. 2020 Jan 21; 10(1): 889. doi: 10.1038/ s41598-020- 57803-3. PMID 31965005

F. Jiménez-Altayó, P. Ortiz-Romero, L. Puertas-Umbert, B. Pérez, E. Vila, P. D’Ocon, V. Campuzano (2019) “Analysis of thoracic aorta function in young Williams-Beuren syndrome mice reveals compromised α1-adrenergic contractions mediated by increased nitric oxide signalling” Scientific Reports (SREP-19-27340, in revision) Q1

M. Dasilva, A. Navarro-Guzman, P. Ortiz-Romero, A. Camassa, A. Muñoz-Cespedes, V. Campuzano, M. V Sanchez-Vives (2019). Altered neocortical dynamics in a mouse model of Williams-Beuren syndrome. Mol. Neurobiol doi: 10.1007/ s12035 -019- 01732-4. PMID: 31471877 Q1

P. Ortiz-Romero, C. Borralleras, M.Bosch-Morató, B. Guivernau, G. Albericio, F. J. Muñoz, L. A. Pérez-Jurado, V.Campuzano (2018). Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model. PLoS One. Mar 19; 13 (3): e0194476. doi: 10.1371/ journal.pone .0194476. PMID:29554110 Q1

C. Borralleras, S. Mato, T. Amédée, C. Matute, C. Mulle, L. A. Pérez-Jurado and V. Campuzano (2016). Synaptic plasticity and Spatial working memory are impaired in the CD mouse model of Williams-Beuren syndrome. Mol Brain: 9(1): 76. PMID:27485321 Q2

Campuzano V  y Estivill X. Bases Moleculares de la Herencia. In the book TRATADO DE MEDICINA INTERNA FARRERAS-ROZMAN XVIII  (pg. 1121-1129). (2016) ISBN: 978-84-8086-487-9

Borralleras, C., Sahun I., Perez-Jurado, L. A and Campuzano V.(2015). Intracisternal Gtf2i Gene Therapy Ameliorates Deficits in Cognition and Synaptic Plasticity of a Mouse Model of Williams-Beuren Syndrome. MOL THER. 23 (11). PMID: 26216516. Q1.

Palacios-Verdu, G. M; Segura-Puimedon, M.; Borralleras, C.; Flores, R.; Del Campo, M.; Campuzano, V. and Perez-Jurado, L. A (2015). Metabolic abnormalities in Williams-Beuren síndrome. J. MED GENT 52 (4): 248-55. doi: 10.1136/ jmedgenet- 2014- 102713 Q1. PMID: 25663682.

Segura-Puimedon M, Sahún I, Velot E, Dubus P, Borralleras C, Rodrigues AJ, Valero MC, Valverde O, Sousa N, Herault Y, Dierssen M, Pérez-Jurado LA, Campuzano V. Heterozygous deletion of the Williams-Beuren syndrome critical interval in mice recapitulates most features of the human disorder. HUM MOL GENET. 2014 Dec 15; 23 (24): 6481-94. doi: 10.1093/ hmg/ ddu368. Q1. PMID: 25027326

  • Offers from the University of Barcelona:

Work UB

  • Offers from the Research Group:

This Group is open for students of the end of Master's, Degree or curricular practices. If you are interested, please contact Victoria Campuzano

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