National Institute of Health Carlos III ( Instituto de Salud Carlos III / ISCIII), Spain

2015

  • Alpha-dystroglycanopathies: Pathophysiology, genetics and studies in animal models
  • Enhancing diagnosis, prognosis and therapy of rare neurodegenerative diseases
  • ENiGMA: Advanced gene editing for Duchenne Muscular Dystrophy
  • Involvement of microRNAs in regulating SERPINA1 gene and its role in alpha-1 antitrypsin deficiency and related lung diseases
  • Multicenter study of Staphylococcus aureus population structure and relationship with microbiome, cocolonización with P. aeruginosa and clinical situation in cystic fibrosis
  • Phenotypic and genotypic characterization of hypohidrotic ectodermal dysplasia in Spanish population

2014

  • Advances Diagnostics Distal Renal Tubular Acidosis (DRTA).
  • Alterations in immune response and hematopoietic development in Wolf-Hirschhorn syndrome: from the animal models to the patients.
  • Bioenergetics regulation as therapeutic target for adrenoleukodystrophy: dissection of E2F1/RIP140 pathways and protection of the mitochondria in the murine model.
  • Biological and radiological markers of cerebrovascular dysfunction in Cerebral Amyloid Angiopathy.
  • Biomarkers study in the pathological continuum between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD)
  • Biotensegrity study in neuroblastoma.
  • Breaking traffic pump copper ATP7B in hepatocytes and variations in Wilson’s disease and idiopathic cuprotoxicosis.
  • Cell stress and mislocalization of transcription factors in ALS pathophysiology.
  • Cerebral functional connectivity in alternative circuitry to food motivation network in adult patients with Prader-Willi syndrome.
  • Clinical-Genetic correlations in inherited dementias and in cognitively preserved nonagenarians.
  • Contribution of mutations in X linked genes versus mutations in autosomes in pairs of brothers with intellectual disabilities without etiology, and no other family history. Study by Next Generation Sequencing.
  • Cystic Fibrosis as a model for the application of advanced therapies to the treatment of rare diseases.
  • Development of new therapeutic strategies for the treatment of Spinal Muscular Atrophy: regulation of autophagy and intracellular signaling pathways.
  • Etiology of neural tube defects: possible implication of the non-canonical Wnt signalling pathway in the incidence of lipomyelomeningocele in humans.
  • Exosomal mRNA and microRNAs ultra-sequencing in patients with Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis caused by identified mutations in CLDN19 gene.
  • Heterogeneity of aortic involvement in Marfan syndrome. Aortic biomechanics, biomarkers and genetic determinants.
  • Identification of new causative genes of Dravet syndrome and related spectrum of infantile febrile epileptic encephalopathies.
  • Impact of Next Generation Sequencing (NGS) for molecular diagnosis in a series of patients affected by genetically unresolved myopathies.
  • Interaction of miRNA-200 and miRNA-138 in infiltration and profiles of Glioblastoma Multiforme MMMI primary. Utility as biomarkers in the diagnosis, prognosis and therapeutic.
  • Intrathecal administration of expanded autologous stromal cells with pauta 100/3 in chronically established spinal cord injury.
  • Inherited syndromes in unexplained sudden cardiac death-genetic investigation.
  • McArdle disease (gsdv): novel diagnostic, pathophysiologic and therapeutic approaches.
  • MicroRNA-based nanotherapy: New treatment for pediatric tumors of the nervous system
  • Mitochondrial encephalomyopathies and secondary coenzyme Q10 deficiencies: Study in pediatric patients, in cellular and murine models.
  • Multitarget chiral compounds for the treatment of neurodegenerative diseases: nicotinic ACh receptors ligands, Nrf2 inducers and antiinflammatory efect.
  • New mutations in the mitochondrial DNA associated to diseases: characterization in transmitochondrial cybrids differentiated to neurons and myocites.
  • New strategies against the multiresistant pathogen Acinetobacter baumannii: siRNA silencing in bacteria and development of new inhibitors. Evaluation in pre-clinical studies.
  • New therapeutic targets in Ewing sarcoma through the study of the tumor microenvironment.
  • Peripheral nerve tumors in Neurofibromatosis 1: susceptibility, origin, progression and malignancy.
  • Pharmacological modulation of ryanodine receptor in Duchenne and Becker muscular dystrophies.
  • Preclinical development of humanized monoclonal antibodies for the treatment of infections caused by Acientobacter baumannii.
  • Risk Factors for Sudden Death in Adults with Congenital Heart Disease. Implications for Automatic Defibrillator Implantation.
  • Role of LINE-1 retrotransposition in DNA-repair associated human diseases.
  • Standardization of the diagnosis of early malignant transformation in neurofibromas of NF1 patients including MRI, PET/CT and Pathology.
  • Study of the genetic susceptibility in the unexplained adenomatous polyposis.
  • Study of the regenerative potential of patient-specific iPS-derived muscle progenitor cells in Limb Girdle Muscular Dystrophy type 2A. Study performed in an in vitro model and in a murine model of tissue injury.
  • Sub-clonal genetic changes in myelodysplastic syndromes (MDS) 5q- patients treated with lenalidomide.
  • Systems biomedicine for unraveling the molecular basis and modeling inherited spastic paraplegias.
  • The oncogenic role of embryonic pathways (Notch, Hedgehog and Wnt) in rhabdomyosarcoma: expanding the knowledge to discover new therapeutic targets.
  • The role of epigenetics in neuroblastoma pathogenesis: new molecular insights for the development of therapeutic strategies.
  • The study of clinical phenotypes and their association with biological distinct pathways in a sample of 200 patients with Autism Spectrum Disorders.
  • Whole exome sequencing for the study of 30 children with developmental delay or moderate to severe

2013

  • Advances in McArdle disease: New therapeutic approaches and development of a new non-invasive diagnostic method in patients
  • Alterations in immune response and hematopoietic development in Wolf-Hirschhorn syndrome: from the animal models to the patients
  • Alzheimer’s disease and Down syndrome. Multimodal cerebrospinal fluid, magnetic resonance imaging and amyloid PET studies
  • An assessment of endometrial cancer risk markers in Lynch syndrome patients
  • Analysis of microRNAs in patients and in murine models of retinitis pigmentosa: novel therapeutic targets
  • Assessment of molecular clonal evolution by next generation sequencing in JAKV617F-positive myeloproliferative neoplasms and correlation with JAK2V617F mutant allele load
  • Clinical and pre-clinical investigation of neuromuscular diseases through computerized image analysis
  • Costs and Burden of Disease study of hereditary angioedema in Spain
  • Cystic and glomerular inherited kidney diseases: panel-based next-generation sequencing to improve diagnosis and exome sequencing to identify novel genes
  • Development of pharmacological therapies for myotonic dystrophy
  • Functional and anatomical preservation of Melatonin and Epigallocatechin Gallate on retinal neurodegenerative models
  • Identification and characterization of microRNAs involved in the pathogenesis of autoimmune thyroid diseases
  • Identification of common genetic alterations (other than NF2 inactivation) in meningiomas and schwannomas derived from patients with NF2 and from sporadic cases
  • Identification of new genes and molecular mechanisms of Usher syndrome and its translation to the diagnosis
  • Identification of new genes responsible for Hirschsprung disease and for thyroid cancer, and elucidation of the associated pathogenic mechanisms
  • In vitro analysis of the protein turnover in muscle of patients with limb girdle muscular dystrophy type 2A
  • Intratumoral heterogeneity in glioblastoma. Therapeutic implications
  • Investigation of RNA splicing and its regulation in multiple myeloma
  • Involvement of ICOS and PI3K isoforms in autoimmune inflammatory diseases. Development of new therapies
  • Living whit Lynch Syndrome: Self-concept, personal identity and adaptation to the generic diagnosis
  • Modeling the impact of telomerase in dyskeratosis congenita: New therapeutic targets and treatments
  • Molecular mechanisms and modulation of mitophagy and mitochondrial biogenesis in cellular models of MELAS disease
  • Molecular diagnostics by massive sequencing (NGS) of genetic eye diseases: retinal dystrophies (DR) and glaucoma. Expression of new variants associated with DR
  • New antigenic reactivities and studies of innate immunity in autoimmune neuromuscular diseases (IMMUN-ENM)
  • New genetic mechanisms involved in imprinting disorders
  • New therapeutic strategies for diffuse intrinsic pontine gliomas and pediatric high grade gliomas
  • Pharmacological modulation of the phosphatase enzyme PP2A as a therapeutic alternative for the treatment of neurodegenerative diseases and brain ischemia
  • Regulation of the autophagic flux in Glioblastoma: towards the identification of novel therapeutical strategies
  • Research of the chromosomal copy number variations and search of new candidate loci in the Familial Colorectal Cancer Type X and in other types of colorectal cancer
  • Resectable Glioblastoma Multiforme: Impact in incorporating advanced functional imaging procedures (RMs; RM-PWI, RM-DWI and PET- Fluorocholine) and genomic Profile in survival
  • Role of (hydroxy)methylation of DNA in the regulation of long non-coding RNAs in Multiple Myeloma
  • Role of collagen VI and biglycan in muscle cell homeostasis: Regulation of muscle cell size and metabolism. Implications for muscular dystrophies
  • Spanish Neuromuscular Disease Database Project
  • Study of HLA-DR/DQ haplotypes in sporadic and familial forms of autoimmune MG. Analysis of their role as genetic factor of susceptibility and modifier of the phenotype in a Spanish population
  • Study of pathways involved in autism spectrum disorders: functional consequences of genetic and epigenetic variants
  • Therapeutic potential of estrogen in Duchenne disease: effects and mechanisms of action on the satellite cells and macrophages
  • Translational research in neuromuscular disorders: advanced dystrophin quantification for streamlined screening of RNA treatments

2012

  • “Tackling teenage”: adaptation of a training program on psychosexual development in ASD adolescents
  • Animal model generation and gene therapy for OXPHOS diseases
  • Antibodies against neuronal membrane antigens in the opsoclonus-myoclonus syndrome, neuromyotonia and epileptic syndromes probably immune mediated
  • Antibodies against neuronal membrane antigens in the opsoclonus-myoclus syndrome
  • Application of new technologies in the characterization of ciliopathies: Bardet-Biedl and Alström syndromes
  • Application of the optic nerve hemoglobin assesment: ischemic optic neuritis and function-morphology relation in glaucoma (coordinated)
  • Cardiac involvement in primary amyloidosis: study of serum biomarkers, 3-Tesla magnetic resonance imaging, and genomic characterization of amyloidogenic light chains.
  • Clinical and etiological research on congenital atypical craniofacial clefts (CACFC)
  • Clinical, neuroanatomical and functional study with neuroimaging techniques in Down Syndrome population with and without dementia: predictive patterns for the development of dementia
  • CoQ10 deficiency syndrome: understanding the genotype-phenotype association and metabolic dysfunction through the generation of iPSCs from patient-specific genetically-corrected cells
  • Drug Repositioning for Rare Disease
  • Effect of HIF modulation on the retinal degeneration of retinitis pigmentosa
  • Effects of neuroinflammation on the activation of the UPR, ERAD and Akt/GSK3/b-catenin pathways in response to proteasome inhibition. Relationship to hippocampal neurodegeneration
  • Exome sequencing for molecular analysis of early epileptic encephalopathies
  • High precission radiosurgical treatment in temporal lobe epilepsy
  • Identification, characterization and clinical relevance of molecular defects in the Complement factor H/CFHR protein family in renal patholog
  • Immunogenetic profiles in hemophagocytic lymphohistiocytosis (HLH) for a rapid diagnosis of the familiar forms (FHL) of the disease
  • Improvement of neural regeneration using biodegradable scaffolds and stem cells during open fetal surgical repair of myelomeningocele in a teratogenic model
  • Long-term morbi-mortality due to hepatic disorders and DILI susceptibility in patients with a previous DILI episode
  • McArdle disease: in-depth phenotype assessment of all Spanish patients and novel therapeutic approaches in patients and in a murine model (‘knock-in’ mouse)
  • Mesenchymal stromal cells as a tool for the treatment of inflammatory/autoimmune diseases: Role of transforming growth factor (TGF)-beta
  • Mitochondrial DNA mutations contribute to autism and also to the characteristics of mitochondrial disorders present in patients with autism spectrum disorders
  • Mitochondrial medicine: delineating a strategy for molecular-genetics identification of oxphos patients; part 1 i+12
  • Mitochondrial medicine: delineating a strategy for molecular-genetics identification of oxphos patients; part 2 vhir
  • Mutation detection in genes associated with Retinitis Pigmentosa by Next generation sequencing (NGS). In vitro expression of mutant gene in human retinal cells
  • Mutational studies in series of patients with distal hereditary motor neuropathy
  • Pathophysiology and genetics of diseases associated with dystroglycan and it’s O-glycosylation
  • Phenotypic and molecular study of thyroid tumors in the PTEN hamartoma tumor syndrome
  • Pluripotent Stem Cells for modeling Charcot-Marie-Tooth disease
  • Progressive Familial Intrahepatic cholestasis type 3: Pharmacological therapy for specific mutations in ABCB4 and identification of new disease-causing genes
  • Role of genetic sequences in postnatal persistence of fetal hemoglobin: Phenotype modulators in hemoglobinopathies
  • SCA36: Analysis of the origin and molecular dynamics of the NOP56 intronic expansion, its influence on gene expression and on the phenotype
  • SPANISH HUMAN PROTEOME PROJECT OF CHROMOSOME 16: Rheumalogic Application
  • Spanish Rare Disease Registries Research Network (website)
  • Structural molecular basis of the kidney dense deposit disease (DDD) associated with C3 polymorphisms and therapeutic opportunities
  • Study of genetic markers in patients with Henoch-Schöenlein purpura
  • Study of miRNAs in Friedreich’s ataxia patients. Diagnostic and therapeutic implications
  • Study on the initial neural affectations in foetal/neonatal hydrocephalus. Prognosis and therapeutic approaches
  • Testing the idoneity of new genomic analysis techniques for the identification of novel genetic determinants of idiopathic GH deficiency and primary IGF-I deficiency in short stature
  • The Molecular Basis for Neurodegeneration and Muscle Atrophy in ALS
  • The role of autophagy and its modulation in fibroblasts from patients with Amyotrophic Lateral Sclerosis and in the NSC-34 cellular model, in a context of normoglycemia or hyperglycemia
  • Therapy approaches for the treatment of mitochondrial DNA depletion syndrome
  • Translational development for detection of aneuploidies through massive parallel sequencing of cell free fetal DNA in maternal plasma
  • Translational Research and disease mechanisms in hereditary peripheral neuropathies
  • Translational Research, Experimental Medicine and Therapeutics on Charcot-Marie-Tooth (website)
  • Usefulness of cerebral flow perfusion maps generated by arterial spin labeling in patients with refractory epilepsy

 

2011

  • Etiology of cardiopathy in acromegaly and its relation to body composition
  • Genetic and epigenetic integrated study of sudden cardiac death
  • Diagnostic potential and reliability of array-CGH technique in chorionic villi samplings. Detection of cryptic chromosome abnormalities and possible fetoplacental discrepancies
  • Analysis of motoneuron degeneration in a cellular model of Spinal Muscular Atrophy
  • Approaching new fetal genetic diagnosis in maternal blood
  • Arteriovenous malformations in patients with Hereditary Hemorrhagic Telangiectasia. Accuracy of different diagnostic techniques
  • Autosomal dominant non-syndromic sensorineural hearing loss: Extension of the molecular-genetic diagnostic by applying novel technologies, functional studies and generation of mouse models
  • Axonal pathophysiology of Friedreich’s ataxia: axonal transport and degeneration
  • Biochemical and genetic characterization of new patients and types of Congenital Disorders of Glycosylation (CDG). Searching new therapeutic targets
  • Biochemical and genetic characterization of new patients and types of Congenital Disorders of Glycosylation (CDG)
  • Clinical utility of the oxidative stress profile and the expression of miRNAs, in blood and exhaled breath condensate in patients with deficiency of alpha-1 antitrypsin
  • Development of innovative Gene Therapy approaches for rare skin disorders
  • Development of Molecular Diagnosis Panels for Hereditary Monogenic Pathology using Fluidigm Access Array System and Next Generation Sequencing GS Junior System
  • FOXC1, FOXC2 y PITX2 gene mutations in primary congenital glaucoma. Identification of new genes by exome sequencing and study of the genotype-phenotype relationship
  • From channel to clinical arrhythmias. Clinical, genetical and functional study of channelopathies
  • Genetic basis of the immunodermatology disorders familial hidradenitis suppurativa and SAPHO syndrome
  • Genomic analysis of Neurofibromatosis type 1 associated tumors: identification of genes involved in tumor predisposition and progression
  • Genomics Analysis in Overgrowth Syndromes: evaluation of genomic dosage through customized oligo/SNP arrays and study of candidate genes using NGS
  • Identification and validation of biomarkers for mitochondrial respiratory chain disorders
  • Identification of new genes responsible for Inherited Retinal Dystrophies and elucidation of the associated pathogenicity mechanisms
  • Identification of the molecular mechanisms that modify the cystic fibrosis phenotype using high-throughput sequence analysis of the exome and transcriptome
  • Idiopathic cardioskeletal myopathies: a clinical, pathological and genetic study
  • Impact of oxidative stress in mitochondrial biogenesis, energy homeostasis and proteolysis and its regulation: therapeutic implications for adrenoleukodystrophy
  • LINE-1 activity in Fanconi Anemia Patients: looking for new partners and establishment of an iPSC based disease model
  • Massive sequencing applied to autosomal recessive and X-linked non-syndromic hearing impairment: identification of novel genes, and development and validation of a diagnostic panel
  • New insights in Fabry disease: molecular mechanisms involved in the pathology and cloning of biological tools for treatment of the pathology
  • Oxidative phosphorylation toxicogenomics in Parkinson’s disease
  • Pathogenesis of Lesch-Nyhan syndrome: hypoxanthine effect on neurotransmission balances during dopaminergic neurone differenciation
  • Phenotypic and molecular characterization of coenzyme Q deficiency syndromes
  • Pilot study of deep sequencing targeted on sequences of high interest for genetic diagnosis of intellectual disability
  • Preclinical characterization of ryanodine receptor stabilizers in patients with muscular dystrophies
  • Preventive and Therapeutic Strategies in Patients with Syndromes Noonan, Costello and Cardio-Facio-Cutaneous
  • Proteomic analysis of serum and urine in patients with acute porphyria
  • Research on Prognostic factors for response to drug therapy in patients with autism spectrum disorder
  • Role of anti-mullerian hormone (amh) as a marker of ovary aging in prenatal screening for Down syndrome
  • Role of mirnas as biomarkers for early diagnosis in hereditary breast cancer. Expression profiling of tumors, blood and serum
  • Study of the importance of autophagy in cells from Parkinson patients with mutations in genes PARK
  • Study on cell mediated immunity diagnosis of pediatric patients with suspected combined immunodeficiency (idc) process
  • The implementation of universal methodologies to Preimplantation Genetic Diagnosis, the best strategy against minority hereditary diseases
  • Translational research in Spinal Muscular Atrophy: phenotype modifiers, iPSCs derived motor neurons and developmental neuromuscular pathology
  • Use of patient-specific induced pluripotent stem cells to improve diagnosis and treatment of hemophilia A

 

2010

  • A mutational study of the TARDBP gene in the familial and sporadic forms of ALS. Analysis of expression in plasma and CSF of the protein TDP-43 as a biomarker for the disease and its correlation with the neuropathological findings
  • Analysis of splicing regulatory sequences (enhancers and silencers) of BRCA1 and BRCA2 by hybrid minigenes: aberrant splicing and breast/ovarian cancer. Global analysis of splicing patterns in BRCA-negative patients
  • Characterization of a new neurodegenerative syndrome linked to R265X mutation in the seipin gene
  • Congenital Myopathies: A study of the signaling pathways & molecular mechanisms involved in its pathogenesis
  • Deciphering the role of the NFkB pathway in autoimmunity: celiac disease as a model
  • Development of a new strategy for the genetic diagnosis of mitochondrial diseases that are caused by nuclear genes
  • Disruption of iodine and thyroid hormone metabolism in a murine model. Implications for Attention Deficit and Hyperactivity disorders (ADHD) and autism
  • Effect of melatonin on the development of uroporphyria in a murine model of porphyria cutanea tarda
  • Etiopathogenic pathways and biomarkers in ALS: genetic expression in patient’s limphocytes and neural stem cell performance from olfactory bulb.
  • Free access to genetic testing through the internet: impact and implications
  • From autism to schizophrenia: Study of the biological mechanisms underlying brain dysfunction and structural phenotypes in schizophrenia and autistic spectrum disorders
  • Functional characterization of oxidative phosphorylation diseases
  • Genetic component search of the Sudden infant death syndrome (SIDS)
  • Genetic study of FXPOI in ovarian follicle cells in young PM carrier women of FXS: Correlation with patients’ clinical parameters
  • Glial cell involvement in Amyotrophic Lateral Sclerosis: a genomics approach
  • GWAS, GWES & GWLA to characterize susceptibility loci for Hirschsprung disease and thyroid cancer.
  • Hereditary Breast and Ovarian Cancer Syndrome: in vitro study of unknown significant BRCA1 and BRCA2 variants and search for new genes responsible for this syndrome
  • Hereditary pyruvate kinase deficiency. Effect of erythropoiesis versus apoptosis balance on the severity of the haemolytic syndrome
  • Immunopathogenesis of lymphocytic enteritis due to gluten-sensitive enteropathy
  • Induction of factor VIII by mesenchimal stem cells transplant in a murine model of hemophilia A
  • Inorganic Polyphosphate as a physiological regulator of von Willebrand Factor, and its role in different subtypes of von Willebrand Disease
  • Integrative genomic and epigenomic approaches to further asses phenotype severity in Spinal Muscular Atrophy (SMA) patients
  • Lentiviral vectors for the development of gene therapy protocols for ataxia-teleangiectasia
  • Mesenchymal Stem Cells for the therapy of Perthes disease. Experimental study
  • Molecular and physiopathological mechanisms of mitophagy in mitochondrial diseases
  • Molecular characterization of imprinting control region(s) for PHP: cis and trans approach
  • Molecular strategy to characterize the genetic base of hereditary disorders of iron metabolism
  • Molecular studies for the treatment of rare diseases of the skin and skin cancer
  • Molecular study of genes involved in Usher syndrome and candidate genes (PDZD7, NCAM2 and MRPL39). Expression studies of USH genes
  • Multiplex lysosomal enzyme genetic analysis using next generation sequencing technology
  • New mutations in the mitochondrial DNA associated to diseases: characterization in transmitochondrial cybrids constructed with immortalized cellular lines and human adult stem cells
  • New study strategies for increasing the frequency of gene targeting (gene correction addressed) in human fibroblasts. Targeted recombination and reprogramming of patient fibroblasts
  • New therapeutic approaches in inherited metabolic disease: RNA-based and pharmacological chaperones therapies
  • Niemann-pick type C disease: generation of a murine model and assessment of a new therapeutic approach
  • Novel insights into muscular dystrophy: role of collagen VI, intramuscular adipose tissue and metabolic dysregulation. Implications for diagnosis and therapies
  • Preclinical evaluation of a therapeutic strategy in limb-girdle muscular dystrophy LGMD2A by gene silencing of cellular systems
  • Regulation of the phenotypic expression in McArdle´s disease: development of experimental models
  • Regulation of the pka pathway as a therapeutic strategy for Huntington’s disease
  • Stem cells like biomarker and/or therapeutic target in Amyotrophic Lateral Sclerosis
  • Study of cerebral functional connectivity in food motivation networks in adult patients with Prader-Willi Syndrome
  • Study of the degeneration of different cone types and rods in animal models of hereditary or acquired retinal degeneration and their protection of with antioxidants, neuroprotectants and antiapoptotic substances
  • Systematic analysis of genetic and epigenetic alterations in autism spectrum disorders
  • Technological innovation of high throughput molecular diagnostics of clinically and molecularly heterogeneous genetic disorders (Techgene): application to mental retardation
  • Therapeutic approach to NF2 with gentamicine and PTC 124 drugs correcting nonsense mutations by readthrough
  • Therapeutic challenge in Leukodystrophies: translational and ethical research towards clinical trials (LeukoTreat)