Research Areas to select

  • Studies on the molecular stratification of systemic autoimmune diseases (PRECISESADS): this study aims at the use of integrated gene expression and methylation data from blood and specific cell populations to define the molecular pathways for each patient´s disease. This will lead us to a new molecular diagnosis and to personalized medicine possibilities. The aim is also to identify classifiers that can be used to determine if a patient may become active or fall into remission, whether long-term or short term. Here the candidate will be involved in the analysis of longitudinal transcriptome data to determine the best molecular pattern to define the evolution of the disease. In addition we are investigating major functional differences between the clusters identified.
  • Molecular Phenotyping of Disease States and the genetics behind each disease state:During period of flare, not all lupus patients fall within the same molecular pattern of disease. We have identified 3 possible molecular patterns: inflammatory, lymphoid and interferon. Each disease state may have a different genetic basis. We have identified a new locus strongly associated in the inflammatory cluster and analyzing the genes involved, while attempting to dissect their function and role in the pathogenesis of the disease. Here the person will be involved in the analysis of single-cell transcriptome data from blood and tissues, according to the patient´s disease state, or exome sequencing of the individuals of interest.
  • Studies on mouse models of SLE: Mouse models of SLE help us understand the mechanisms of disease. We have been working on the role of the BANK1 gene and the appearance of various subsets of B cells, including pro-inflammatory B cells and regulatory B cells. In addition, the role of the microbiome in the development and differentiation of B cell subsets in the spleen but also kidney and intestine, including single-cell RNASeq.

Relevant publications:

Kozyrev, S.V*., Abelson, A.K*., Wojcik, J., Zaghlool, A., Linga Reddy, P.M.V., Sanchez, E., Yin, H., Gunnarsson, I., Svenungsson, E., Sturfelt, G., Jönsen, A., Truedsson, L., Pons-Estel, B., Witte, T., D’Alfonso, S., Momigliano-Richiardi, P., Danieli, M.G., Gutierrez, C., Suárez, A., Junker, P., Laustrup, H., González-Escribano, M.F., Martin, J., Abderrahim, H., and Alarcón-Riquelme, M.E. The B Cell Gene BANK1 is Associated with Systemic Lupus Erythematosus Through the Effect of Several Functional Variants Nat Genet 40(2):211-6, 2008

Bentham, J., Morris, D.L., Cunninghame-Graham, D.S., Pinder, C.L., Tombleson, P., Behrens, T.W., Criswell, L.A., Gaffney, P., Martin, J., Fairfax, B., Knight, J., Syvannen, AC., Ronnblom, L., Graham, R.R., Wither, J.E., Rioux, J.D., Alarcón-Riquelme, M.E., and Vyse, T.J. Genetic Association Analyses Implicate aberrant gene regulation of the innate and adaptive immunity genes in the pathogenesis of SLE implicated by genetics. Nat Genet 47: 1457–1464, 2015.

Toro, D., Martorell-Marugán, J., Goldman, D., Petri, M., Carmona-Sáez, P., and Alarcón-Riquelme, M.E. Longitudinal Stratification of Gene Expression Reveals Three SLE Groups of Disease Activity Progression Arthritis Rheum 70(12):2025-2035, 2018.

Barturen, G., Beretta, L., Cervera, R., Van Vollenhoven, R., and Alarcón-Riquelme, M.E. Moving Towards a Molecular Taxonomy of Autoimmune Rheumatic Diseases. Nat Rev Rheumatol 14(2):75-93, 2018.

Toro-Domínguez, D., Domínguez-López, R., García Moreno, A., Villatoro-García, J.A., Martorell-Marugán, J., Goldman, D., Petri, M., Wojdyla, D., Pons-Estel, B.A., Isenberg, D., Morales-Montes de Oca, G., Trejo-Zambrano, M.I., García González, B., Gómez-Martín, D., Romero-Díaz, J., Carmona-Saez, P., and Alarcón-Riquelme, M.E. Differential Treatments and Risk for Severe Nephritis Based on a Longitudinal Systemic Lupus Erythematosus Stratification. Sci Rep 9(1): 15502, 2019.

Barturen G, Babaei S, Català-Moll F, Martínez-Bueno M, Makowska Z, Martorell-Marugán J, Carmona-Sáez P, Toro-Domínguez D, Carnero-Montoro E, Teruel M, Kerick M, Acosta-Herrera M, Le Lann L, Jamin C, Rodríguez-Ubreva J, García-Gómez A, Kageyama J, Buttgereit A, Hayat S, Mueller J, Lesche R, Hernandez-Fuentes M, Juarez M, Rowley T, White I, Marañón C, Gomes Anjos T, Varela N, Aguilar-Quesada R, Garrancho FJ, López-Berrio A, Rodriguez Maresca M, Navarro-Linares H, Almeida I, Azevedo N, Brandão M, Campar A, Faria R, Farinha F, Marinho A, Neves E, Tavares A, Vasconcelos C, Trombetta E, Montanelli G, Vigone B, Alvarez-Errico D, Li T, Thiagaran D, Blanco Alonso R, Corrales Martínez A, Genre F, López Mejías R, Gonzalez-Gay MA, Remuzgo S, Ubilla Garcia B, Cervera R, Espinosa G, Rodríguez-Pintó I, De Langhe E, Cremer J, Lories R, Belz D, Hunzelmann N, Baerlecken N, Kniesch K, Witte T, Lehner M, Stummvoll G, Zauner M, Aguirre-Zamorano MA, Barbarroja N, Castro-Villegas MC, Collantes-Estevez E, de Ramon E, Díaz Quintero I, Escudero-Contreras A, Fernández Roldán MC, Jiménez Gómez Y, Jiménez Moleón I, Lopez-Pedrera R, Ortega-Castro R, Ortego N, Raya E, Artusi C, Gerosa M, Meroni PL, Schioppo T, De Groof A, Ducreux J, Lauwerys B, Maudoux AL, Cornec D, Devauchelle-Pensec V, Jousse-Joulin S, Jouve PE, Rouvière B, Saraux A, Simon Q, Alvarez M, Chizzolini C, Dufour A, Wynar D, Balog A, Bocskai M, Deák M, Dulic S, Kádár G, Kovács L, Cheng Q, Gerl V, Hiepe F, Khodadadi L, Thiel S, de Rinaldis E, Rao S, Benschop RJ, Chamberlain C, Dow ER, Ioannou Y, Laigle L, Marovac J, Wojcik J, Renaudineau Y, Borghi MO, Frostegård J, Martín J, Beretta L, Ballestar E, McDonald F, Pers JO, Alarcón-Riquelme ME. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases. Arthritis Rheumatol 73(6):1073-1085, 2021.

Morell, M., Varela, N., Coppard, C., Castillejo-López, C., Wu, Y.Y., Luque, M.J., García, M.A., Alarcón-Riquelme, M.E., and Marañón, C. SIDT1 is a Key Player in Interferon Responses to TLR7 and TLR9. eBIOMedicine 76:103808. doi: 10.1016/j.ebiom.2021.103808.

Technology platforms

    • The NExtSeq 500: Next-Generation Sequencing from Illumina
    • The iScan System from Illumina
    • Mass cytometry (Cytof/Helios) from Fluidigm
    • Flow cytometry: sorting, flow and imaging
    • Bioinformatics analyses, enough capacity, servers
  • Confocal microscopy
  • Animal models of SLE

Funding

    • Ministerio de Economía y Competitividad, Plan Estatal de fomento de la Investigación Científica de Excelencia 2020, Spain (2021-2023)
  • Innovative Medicines Initiative Program of the European Unión (2014-2018): special funding of the project PRECISESADS
  • Innovative Medicines Initiative Program of the European Union (2019-2026): special funding of the project 3TR (PI)

 Additional information

International Collaborations: Dr Alarcón-Riquelme heads the Managing Entity of the IMI funded project PRECISESADS, on the “Molecular Re-classification of Systemic Autoimmune Diseases” which joins 21 European academic groups, 2 SMEs and 5 Big Pharma. She is also the coordinator of 3TR: Taxonomy, Treatment, Targets, and Remission: Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions. The project joins 58 European academic groups, 3 biotechnology companies and 8 pharmaceutical companies.

Dr. Alarcón-Riquelme is also a member of the Spanish Society of Rheumatology, The Spanish Society of Immunology, part of the Executive Board of SLEuro, Associate Editor of Arthritis & Rheumatology, member of the Board of Rheumatology.

Links:

Whom to contact: Prof Marta E. Alarcón-Riquelme at This email address is being protected from spambots. You need JavaScript enabled to view it.

Requirements for secondment: The usual languages are Spanish and English. The student will need to have an insurance to cover any possible accidents within the Center, separate from the insurance during the stay in Spain.