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Mechanisms of Disease

Gene Regulatory Control in Disease (GeneControl)

Ashwin Woodhoo
Group Leader | Oportunius researcher
ashwin.woodhoo@usc.es
 
Labs: P1L8, P1L9
Field of knowledge

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 at work in the cell. Its disruption therefore often leads to disease.

Using both experimental and computational approaches, our laboratory aims to deconstruct the mechanistic basis for control of gene expression in developmental and pathological contexts at the level of single genes to entire genomes. We are interested in multiple aspects of gene expression control, including transcriptional, translational and post-translational control mechanisms with a particular focus on nerve disorders, liver disease and cancer.

Research Lines

  • Nerve Disorders: The work in the laboratory addresses a set of interlocking issues in Schwann cell biology, ranging from axonal myelination to the response of Schwann cells to pathological conditions, including nerve injury, genetic disorders, immune cell attack and microbial infections.
  • Liver Disease: We are investigating the molecular mechanisms underlying the hepatic cellular responses to chronic liver diseases of various etiologies, including non-alcoholic fatty liver disease (NAFLD), drugs, and cholestatic disease, as well as the hepatic regenerative response after liver resection.
  • Cancer: We are focused on the identification of therapeutical targets for neurofibromatosis type 1 and malignant peripheral nerve sheath tumours (MPNST) Our research employs a variety of model organisms (mice models and patient samples) and is built on a multidisciplinary approach involving an array of modern techniques in biochemistry and molecular, cellular, and structural biology, as well as bioinformatic analyses, high-throughput sequencing and -OMICS technologies.

Members

Marta Varela Rey
Sergio Vidal Distinguished Investigator
martavarela.rey@usc.es
Cristina Riobello Suárez
Postdoctoral research associate
cristina.riobello@usc.es
Hector Fernández Susavila
Postdoctoral research associate
hectorfernandez.susavila@usc.es
Izaskun Buendia Abaitua
Juan de la Cierva researcher
izaskun.buendia@usc.es
Sergio Velasco Avilés
Postdoctoral research associate
sergio.velasco@usc.es
Vanesa Álvarez Álvarez
Postdoctoral research associate
vanesa.alvarez.alvarez@usc.es
Adrián Posado Fernández
Project Management Technician
adrian.posado@usc.es

 

Alejandro Sánchez Rueda
FPI fellowship
Paula Ayuso García
FPU fellowship
Jorge Cañas Martín
PhD student
Joan Blázquez Vinces
Xunta de Galicia fellowship
Aroa Ferrrer Pinós
FPU fellowship
Cecilia Huarte Sebastián
FPU fellowship
Alba Capelo Diz
PhD student
Alberto Tinahones Ruano
AECC fellowship
Selene Jiménez Vega
Xunta de Galicia fellowship
Noelia Otero Rial
Lab technician
Adrián Aparicio Rey
AECC fellowship
Eva María Esquinas Román
FPI fellowship
Carlos Rodríguez Ponte
Lab technician
Raquel Peña Romero
FPU fellowship
Yuqing Wang
Marie Curie PhD student fellowship
Sofia Perdikari
Marie Curie PhD student fellowship

Selected publications

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

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*. [* joint senior authors]

HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. 

Palomo-Irigoyen et al,…,Varela-Rey M* & Woodhoo A*. [* joint senior authors]

Methionine and SAMe levels are critical regulators of PP2A activity modulating lipophagy during steatosis. 

Zubiete-Franco I & García-Rodríguez JL, …, Martínez-Chantar ML* & Varela-Rey M* [* joint senior authors]

Schwann cell autophagy, myelinophagy, clears myelin. 

Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo_irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias N, Azkargorta M, Aurrekoetxea I, Jefferies HBJ, Aspichueta P, Elortza F, Aransay AM, Martínez Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A*, Jessen KR*. [* joint senior authors]

S-adenosylmethionine Regulate the Schwann Cell DNA Methylome.

Varela-Rey M*, Iruarrizaga-Lejarreta M*, Lozano JJ*, Aransay AM*, Fernandez AF, Lavin JL, Mosen-Ansorena D, Berdasco M, Turmaine M, Luka Z, Wagner C, Lu SC, Esteller M, Mirsky R, Jessen KR, Fraga MF, Martinez-Chantar ML, Mato JM, and Woodhoo A

The RNA-binding protein human antigen R controls global changes in gene expression during Schwann cell development. 

Iruarrizaga-Lejarreta M, Varela-Rey M, Lozano JJ, Fernandez-Ramos D, Rodriguez-Ezpeleta N, Embade N, Lu SC, van der Kraan PM, Blaney Davidson EN, Gorospe M, Mirsky R, Jessen KR, Aransay AM, Mato JM, Martinez-Chantar ML and Woodhoo A.

Human antigen R contributes to hepatic stellate cell activation and liver fibrosis. 
Hepatology.

Woodhoo A, Iruarrizaga-Lejarreta M, Beraza N, Garcia-Rodriguez JL, Embade N, Fernandez-Ramos D, Martinez-Lopez N, Gutierrez-De Juan V, Arteta B, Caballeria J, Lu SC, Mato JM, Varela-Rey M* and Martinez-Chantar ML* [* joint senior authors]

A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo. 

Napoli I, Noon LA, Ribeiro S, Kerai AP, Parrinello S, Rosenberg LH, Collins MJ, Harrisingh MC, White IJ, Woodhoo A and Lloyd AC

c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. 

Arthur-Farraj PJ, Latouche M, Wilton DK, Quintes S, Chabrol E, Banerjee A, Woodhoo A, Jenkins B, Rahman M, Turmaine M, Wicher GK, Mitter R, Greensmith L, Behrens A, Raivich G, Mirsky R and Jessen KR

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.

Woodhoo A, Alonso MB, Droggiti A, Turmaine M, D'Antonio M, Parkinson DB, Wilton DK, Al-Shawi R, Simons P, Shen J, Guillemot F, Radtke F, Meijer D, Feltri ML, Wrabetz L, Mirsky R and Jessen KR

Selected Results

Projects

UE project(s)

Deconstructing the Translational Control of Myelination by Specialized Ribosomes (MyeRIBO)
REF: 865157Duration: -
PI: Ashwin Woodhoo
European Commission

National project(s)

Papel funcional y mecanístico de los IncRNAs en la enfermedad colestática RETOS 2020
REF: PID2020-119486RB-I00Duration: -
PI: Marta Varela Rey
AGENCIA ESTATAL DE INVESTIGACION
Estudiar cómo el control de translación por ribosomas especializados en células gliales del siste...
REF: JC2019-041873-IDuration: -
PI: Izascun Buendía Abaitua
AGENCIA ESTATAL DE INVESTIGACION

Contracts Agreements Services

Convenio de colaboración entre a Consellería de Cultura, Educación e Universidade e a Universidad...
REF: 2021-CP089Duration: -
PI: Ashwin Woodhoo
CONSELLERIA DE CULTURA, EDUCACION E UNIVERSIDADE