C046 – Gene Regulatory Control in Disease (GeneRegulon)

Objeticves and lines of research

Objectives

The regulation of gene expression is key to understanding cell behavior. It is precisely controlled to ensure that specific genes are expressed at the appropriate times and levels in response to various genetic and environmental signals, which determines the biological processes that operate in the cell. Therefore, its alteration often leads to disease.
Using both experimental and computational approaches, our laboratory aims to deconstruct the mechanistic basis for the control of gene expression in pathological and developmental contexts at the level of individual genes to complete genomes.

Lines of research

We are interested in multiple aspects of gene expression control, including transcriptional, translational and post-translational control mechanisms, with a particular focus on nervous disorders, liver diseases and cancer.

1. Nerve Disorders: Work in the laboratory addresses a number of intertwined problems in Schwann cell biology, ranging from axonal myelination to Schwann cell response to pathological conditions, including nerve injury, disorders genetics, immune cell attack and microbial infections.

2. Cancer: We are focused on identifying therapeutic targets for neurofibromatosis type 1 and malignant peripheral nerve sheath tumors (MPNST).

3. Liver disease: We are investigating the molecular mechanisms underlying liver cellular responses to chronic liver diseases of various etiologies, including non-alcoholic fatty liver disease (NAFLD), drugs and cholestatic disease, as well as the liver regenerative response after liver resection.

Research team

Leader
Woodhoo, Ashwin

Researchers (established or associate)
Varela Rey, Marta

Postdoctoral staff
Buendia, Izaskun
Fernández Susavila, Héctor
Riobello Suárez, Cristina
Velasco Avilés, Sergio

Predoctoral staff
Aparicio Rey, Adrián
Ayuso García, Paula
Blázquez Vicens, Joan
Capelo Diz, Alba
Esquinas Román, Eva María
Huarte Sebastián, Cecilia
Jiménez Vega, Selene
Ferrer Pinós, Aroa
Lis López, Lluis Miquel
Tinahones Ruano, Alberto Jesús
Sánchez Rueda, Alejandro

Technical support staff
Cañas Martín, Jorge
Posado Fernández, Adrián

Projects

Identification of new predictors of hepatic fibrosis
Entidad financiadora: Fundación BBVA
Investigador/a principal: Marta Varela Rey

Publications
  • Stassart RM, Woodhoo A. Axo-glial interaction in the injured PNS. Dev Neurobiol. 2021 Jul;81(5):490-506. doi10.1002/dneu.22771
  •  Palomo-Irigoyen et al,…,Varela-Rey M & Woodhoo A. HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. Journal of Clinical Investigation (2020) 130(7):3848–3864. doi: 10.1172/JCI130379
  • Goikoetxea-Usandizaga N, Serrano-Maciá M, Delgado TC, Simón J, Fernández Ramos D, Barriales D, Cornide ME, Jiménez M, Pérez-Redondo M, Lachiondo-Ortega S, Rodríguez-Agudo R, Bizkarguenaga M, Zalamea JD, Pasco ST, Caballero-Díaz D, Alfano B, Bravo M, González-Recio I, Mercado-Gómez M, Gil-Pitarch C, Mabe J, Gracia-Sancho J, Abecia L, Lorenzo Ó, Martín-Sanz P, Abrescia NGA, Sabio G, Rincón M, Anguita J, Miñambres E, Martín C, Berenguer M, Fabregat I, Casado M, Peralta C, Varela-Rey & M Martínez-Chantar ML. Mitochondrial bioenergetics boost macrophages activation promoting liver regeneration in metabolically compromised animals. Hepatology. 2021 Sep 12. doi: 10.1002/hep.32149
  • Blokker BA, Maijo M, Echeandia M,…,Varela-Rey M, Beraza N. Fine-Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease. Hepatology, (2019)  Feb;69(2):699-716. doi: 10.1002/hep.30275
  • Gonzalez-Rellan MJ, Fondevila MF, Fernandez U, Rodríguez A, Varela-Rey M, Veyrat-Durebex C, Seoane S, Bernardo G, Lopitz-Otsoa F, Fernández-Ramos D, Bilbao J, Iglesias C, Novoa E, Ameneiro C, Senra A, Beiroa D, Cuñarro J, Dp Chantada-Vazquez M, Garcia-Vence M, Bravo SB, Da Silva Lima N, Porteiro B, Carneiro C, Vidal A, Tovar S, Müller TD, Ferno J, Guallar D, Fidalgo M, Sabio G, Herzig S, Yang WH, Cho JW, Martinez-Chantar ML, Perez-Fernandez R, López M, Dieguez C, Mato JM, Millet O, Coppari R, Woodhoo A, Fruhbeck G, Nogueiras R. O-GlcNAcylated p53 in the liver modulates hepatic glucose production. Nat Commun. 2021 Aug 20;12(1):5068. doi: 10.1038/s41467-021-25390-0
  • González-Romero F, Mestre D, Aurrekoetxea I, O’Rourke CJ, Andersen JB, Woodhoo A, Tamayo-Caro M, Varela-Rey M, Palomo-Irigoyen M, Gómez-Santos B, de Urturi DS, Núñez-García M, García-Rodríguez JL, Fernández-Ares L, Buqué X, Iglesias-Ara A, Bernales I, De Juan VG, Delgado TC, Goikoetxea-Usandizaga N, Lee R, Bhanot S, Delgado I, Perugorria MJ, Errazti G, Mosteiro L, Gaztambide S, Martinez de la Piscina I, Iruzubieta P, Crespo J, Banales JM, Martínez-Chantar ML, Castaño L, Zubiaga AM, Aspichueta P. E2F1 and E2F2-Mediated Repression of CPT2 Establishes a Lipid-Rich Tumor-Promoting Environment. Cancer Res. 2021 Jun 1;81(11):2874-2887. doi: 10.1158/0008-5472.CAN-20-2052
  • Simon J, Nuñez-García M, Fernández-Tussy P, Barbier-Torres L, Fernández-Ramos D, Gómez-Santos B, Buqué X, Lopitz-Otsoa F, Goikoetxea-Usandizaga N, Serrano-Macia M, Rodriguez-Agudo R, Bizkarguenaga M, Zubiete-Franco I, Gutiérrez-de Juan V, Cabrera D, Alonso C, Iruzubieta P, Romero-Gomez M, van Liempd S, Castro A, Nogueiras R, Varela-Rey M, Falcón-Pérez JM, Villa E, Crespo J, Lu SC, Mato JM, Aspichueta P, Delgado TC, Martínez-Chantar ML Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly. Cell Metab. 2020 Mar 3;31(3):605-622.e10. doi: 10.1016/j.cmet.2020.01.013
  • Myelin – Methods and Protocols in Methods in Molecular Biology, edited by A. Woodhoo, Springer (2018). ISBN 978-1-4939-7862-5