Línies de recerca

• Critical conditions for disease onset or prognosis

  To evaluate clinical and molecular features that may condition disease onset, severity, evolution and co-morbidities. Description of the natural history of disease, elaboration of clinical guidelines for patient management, participation in clinical assays and registries.

• Identification of genes responsible for genetic disorders

  The strategic objective of this research line is to investigate the genetic, anatomopathological and biochemical bases, as well as the physiopathological mechanisms of inherited metabolic diseases and muscular disorders. Within this group we are particularly devoted to patients with defects of the mitochondrial energy metabolism, congenital disorders of glycosylation (CDG) and myositis. These patients are preselected on the basis of their clinical and biochemical or anatomopathological characteristics. Within this line, we aim to identify new genetic defects and to generate knowledge that could be implemented to improve the diagnosis and the design of therapeutic options.

• Physiopathology of disease

  To search for the physiopatological bases of these diseases we use a combination of the classical and advanced omics technologies (metabolomics, proteomics, transcriptomics, genomics) together with functional biology. In addition, we aim to consolidate a platform of generic tools for functional genomics approaches to determine the pathogenic effect of the genetic variants and molecular mechanisms. We are specially focused in understanding mitochondrial disorders of primary or secondary origin, but also alternative molecular basis of disease.

• Validation of models, mechanisms, and biomarkers of disease

  To confirm the pathogenicity of a certain gene or molecular mechanism, we validate cell models derived from patient to study the disease. We use fibroblasts, pluripotent induced stem (iPS) cells, neuronal or muscular cells derived from iPS, as well as 3D-organoids. These models also prompt the identification of potential surrogate biomarkers of disease, that are latter seek in biological fluids (liquid biopsy).

• Therapeutic approaches

  This line involves the testing of chemical and peptide libraries, as well as genetic edition strategies. Selection has been made on disease-causing missense mutations previously identified by our group in a wide range of diseases. We are particularly interested in compounds with chaperone action and compounds capable of inducing lysosomal exocytosis, autophagy and anti-oxidant stress response, that we assay in the models of disease previously developed. When necessary, preclinical studies will be performed.