Genetics and Genomics of Immune-Mediated Diseases

The understanding of the genetic architecture of disease and the mechanisms through which genes lead to the development of specific cellular populations and the pathways through which these do so, is of major importance to the application of new therapies, the early diagnosis of diseases with very late diagnostic rates, and the understanding of the mechanisms of susceptibility genes in the pathogenesis of disease and the molecular stratification of diseases also including those who never receive a clinical diagnosis, are important questions that require innovative approaches and multidisciplinary collaborations.

Dr Alarcón-Riquelme has coordinated a European Innovative Medicines Initiative (IMI-JU) funded project known as PRECISESADS (2014-2019) with the participation of the pharma industry and up to 20 academic centers around Europe with a budget of 22M€.

In this study, through the molecular reclassification of systemic autoimmune diseases the group identified new genetic loci involved in inflammation, and groups of individuals who shared molecular signatures, despite having different clinical diagnoses.

The results of this work are now part of the applied personalized medicine research line (SL3). Here, Prof. Alarcón-Riquelme coordinates a major study, 3TR (2019-2026), the largest in the topic of immunology funded by the IMI-JU and major pharmaceutical companies with a budget of 80M€ where 7 immune-mediated diseases are being prospectively studied and analyzed for the mechanisms of response and non-response to treatments.

Dr Alarcón has also a separate collaboration with Astra Zeneca to sequence the genome of several systemic autoimmune and inflammatory diseases and determine proteome modifications that may help identify novel therapeutic targets. Dr Alarcón received recently funding from the Lupus Research Alliance from the United States to perform single cell analyses of responses and non-response to treatments in SLE in paired blood and tissues of active patients. Various collaborations are ongoing with Latin America. Focusing on publications in D1.

Despite being relatively rare diseases, systemic autoimmune diseases in conjunction reach about 5% of the population, particularly young and middle-aged women. Immune-mediated diseases affect the complete sphere of diseases, from all organs and systems where an inflammatory process is taking place. Many patients remain several years without a diagnosis and are therefore not treated with new biological drugs, while it is molecularly evident that they do have abnormalities in their immune system cellular patterns of the transcriptome. Earlier diagnosis and proper treatment are some of the social goals my group has. Possibility of predicting treatment responses will be of major importance to initiate the correct therapy and early to avoid organ damage.

Prof Alarcón-Riquelme has trained over 15 PhD students and a large number of postdocs. Her group is composed of 3 senior researchers (Guillermo Barturen, Elena Carnero and Concepción Marañón), each co-supervising PhD and masters students and 5 PhD students. Dr Alarcón-Riquelme is the PI of a Marie Sklodowska Curie predoctoral network called SIGNATURE co-coordinated by Dr Concepción Marañón.

Promote senior researchers in the group to apply for national, regional, and European grants, including ERC grants. Increase contacts with the pharmaceutical industry and with international collaborators in the areas of immune-mediated diseases. Obtain new European funding. Continue with the training of PhD students and postdocs. Keep the level of MdM guarantor.