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Research Group on Human Genetics and Disease Models - GEHUMEN

Description

Basic research in genetic diseases with neurological alterations. Our group mainly studies the Friedreich's Ataxia and Spastic Paraplegia Type 7 diseases, which are rare mitochondrial pathologies with Mendelian inheritance, and Schizophrenia, relatively more frequent, but whose inheritance is complex. Friedreich's Ataxia (FRDA): Through the development of different experimental models of the disease (animal models created in Drosophila and cell models from lines of human origin), we generate tools that allow us to address:

  1. The identification of genes that, by altering their expression, can increase the level of frataxin, a protein deficient in FRDA, or improve some of the pathological phenotypes in the models. 
  2. The search for new molecules with therapeutic potential to be proposed in preclinical trials, together with a methodological strategy that facilitates the identification of the molecular mechanism underlying the action of these molecules. 
  3. The identification of new targets that make it possible to design different therapeutic strategies.

Spastic Paraplegia Type 7 (SPG7): It is a neurodegenerative disease caused by mutations in the SPG7 gene that encodes the paraplegin protein. So far, the only models described are those of total loss of paraplegia function due to a complete deletion of the gene. However, the effects caused by complete loss of function may be different from those caused by a particular point mutation. New mass sequencing methodologies identify genetic changes that are often difficult to characterise as pathological. Our aim is to use Drosophila to assess the possible pathogenic effect of genetic variations identified in the SPG7 gene in patients with the disease. In addition, these humanised Drosophila models will make it possible to understand the pathological mechanism of these mutations in order to propose actions aimed at a more personalised medicine.

Schizophrenia: This disease is clinically very heterogeneous with complex inheritance involving factors of different aetiology. The identification of genetic risk factors is still a challenge. Our group carries out, in chronic patients and in patients with first psychotic episodes, expression studies of candidate genes that have been identified in Genome Wide Association Studies (GWAS). We also analyse the effect of medication on gene expression patterns in blood samples by identifying biomarkers of treatment response. By generating Induced Pluripotent Stem Cells (iPSCs) from psychotic patients and healthy individuals, differentiated into different neuronal types (inhibitory, excitatory and dopaminergic), the group aims to understand why some patients respond to medication while others are totally refractory to treatment.

Goals CT
  • Identification of modifier genes, new targets and molecules with therapeutic potential in Friedreich’s Ataxia.
  • Identification of the pathological mechanisms of Spastic Paraplegia Type 7.
  • Identification of genetic risk factors and biomarkers of response to medication in Schizophrenia.
Research lines
  • Experimental models in mitochondrial neurodegenerative diseases

    Obtaining experimental models and characterisation of the effects produced by:

    • Systemic and tissue-specific loss/gain of frataxin and paraplegia function in Drosophila.
    • Functional alterations of both proteins in humanised paraplegia and frataxin models in Drosophila.
  • Genetics of Schizophrenia

    Study of gene expression, identification of biomarkers of treatment response in schizophrenia, and characterisation of the cell response to the drug in models derived from Induced Pluripotent Stem Cells (iPSCs).

Management
  • MOLTO RUIZ, MARIA DOLORES
  • PDI-Catedratic/a d'Universitat
View details
 Contactedolores.molto@uv.es
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  • MOLTO RUIZ, MARIA DOLORES
    PDI-Catedratic/a d'Universitat
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Investigation activities

Associated structure
Contact group details
Human Genetics and Disease Models (GEHUMEN)

Burjassot/Paterna Campus

C/ Doctor Moliner, 50

46100 Burjassot (València)

+34 963 543 400

Geolocation

dolores.molto@uv.es

Contact people
  • MOLTO RUIZ, MARIA DOLORES
  • PDI-Catedratic/a d'Universitat
View details
 Contactedolores.molto@uv.es