Liver, Digestive and Inflammatory Diseases

General Immunology and Transplants


Cód. SSPA: IBiS-E-03

Research Lines

  • Our principal research area is the study of the molecular pathways involved in inflammatory-based diseases development

Specifically, we have focused on studying genes associated with rheumatoid arthritis, systemic lupus erythematosus, Chron's and Behcet's diseases, as well as infection by hepatitis C virus. Traditionally, the approach was the study of candidate genes based on the function of the molecules they encode using low-throughput studies (conventional PCR and real-time PCR). In most recent projects, we used medium (Sequenom iPlex MassARRAY) and high throughput (Immunochip) platforms to simultaneously study a large number of polymorphisms located in genes related to nucleic acid sensors and perform exhaustive screening of a large number of variants of immune system genes. Finally, we have introduced the Next Generation Sequencing (NGS) for the rare variants investigation. These types of studies have made it possible to verify the existence of common routes to different immune-mediated pathologies.

Currently, we are focusing on the study of autoinflammatory diseases. These diseases, mainly monogenic, are caused by genetic variants in genes related to the innate branch of the immune system, specifically, in components of the inflammasome pathways. There are multiple issues related to this area that pose problems even in clinical practice, thus the variants of uncertain significance or heterozygous individuals with a disease phenotype in pathologies with a recessive inheritance pattern. We are currently developing functional studies to establish phenotype/genotype relationships in vitro models.

The tools used in our laboratory consisted of genotyping platforms of different scales, Sanger and massive sequencing and RNA expression studies. We have also experienced the isolation and analysis of cell subpopulations and cell cultures.

  • Immune response in solid organ and hematopoietic cell transplantation 

Rejection is the leading cause of organ failure after transplantation. The criteria for diagnosis of antibody-mediated rejection (AMR) in liver transplantation includes donor-specific glutathione S-transferase T1 (GSTT1) antibodies. These antibodies were identified in our laboratory in 2001. This antigen is also involved in AMR of the kidney allograft and in the hepatic form of graft-versus-host disease. We have also described other genetic mismatches between donor and recipient leading to antigen recognition and rejection.

Presently, my main area of research is the study of the mechanisms leading to this particular immune response. We have incorporated new techniques such as cytometry by time of flight (Cytof) which allows the analysis of a high number of cellular markers simultaneously and whole genome sequencing in the search for new allelic mismatches between donor and recipient that experience chronic ductopenic rejection after LT.

For us, this is the result of years of research, from which the patients in our hospital already benefit, since the Liver Transplant Unit, the Digestive Diseases Service and ourselves have worked closely all these years.

  • We study the role of homeostatic processes and immunoregulation in different clinical settings

As the chronic immunodeficiency in people living with HIV or the immunosuppression in renal transplant recipients, as well as in “aging”. In all these scenarios, the alterations in immune homeostasis and regulation impact systemic inflammation and cellular senescence, eventually affecting tissue function and clinical progression. Our main line of research is T-cell homeostasis, involving central mechanisms as thymic output as well as peripheral mechanisms like compensatory homeostatic proliferation and regulatory T-cells, among others. We actively collaborate with the Biochemistry and Nephrology Services at our Hospital as well as with different Elderly Homes. Our research approaches mainly involve multiparametric flow cytometry as well as different primary cell culture and molecular techniques, including omics.

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