CO16: Genetics, Epigenetics and Transcription in Brain Diseases

The group is led by a specialist in Immunology, and in recent years our group has been analyzing the regulatory functions of the LAT and NTAL membrane adapters, as well as their relationship with the Lck kinase in the transmission of intracellular signals associated with immune receptors. . Our lines of research aim to deepen the knowledge of the regulatory functions of intracellular signals in lymphocytes, and analyze the implications in some immune-based pathologies such as rheumatoid arthritis (RA).

Our lines of research include in vitro studies, through the use of tumor cell lines, work with mice, and analysis of lymphocytes from healthy donors and patients with immune-based pathologies. We have ongoing international collaborations with groups in France (Drs. Bernard and Marie Malissen, CIML, Marseille, France), UK (Dr. Michael Dustin, Univ. of Oxford, UK) and Poland (Dr. Arkadiusz Miazek, Univ. of Wrocław, Poland). Our work may be useful not only for a better understanding of the molecular mechanisms governing T cell activation, but also for gaining insight into altered immune mechanisms in RA and potentially other immune-based pathologies.

• Enrique Aguado Vidal:
• E-mail: enrique.aguado@uca.es.
• ORCID: 0000-0002-7232-2661.

• Early intracellular signaling in T and B lymphocytes: implications in immunologically based pathologies.
• Transmembrane adapter proteins and their role as regulators of activation in lymphocytes.
• In vivo analysis of elements of the intracellular signaling cascade associated with immune receptors.

TCR/CD3 Immunopathology Intracellular signaling Membrane Adapters

• Principal Investigators:
  • Enrique Aguado Vidal (PI).
• Postdoctoral Researchers:
  • Miguel Martínez de Arbulo Echevarría.
  • Isaac Narbona Sánchez.
• Predoctoral Researchers:
  • Inmaculada Vico Barranco.
  • Luis Miguel Fernández Aguilar.
  • Mª Isabel Serrano García.
  • Alba Pérez Linaza.
• Technical Support Staff:
  • Mª Carmen López Osuna (Technician).
  • José L. Poveda Díaz (Technician).

• Estudio de los mecanismos reguladores intrínsecos de la cascada de señalización del complejo TCR/CD3; implicaciones en artritis reumatoide (InRegMec-TCR-RA). PRINCIPAL INVESTIGATOR: Enrique Aguado Vidal. FUNDING ENTITY/PROGRAM: Ministerio de Ciencia e Innovación, PROYECTOS DE I+D+i. CENTER: Universidad de Cádiz. REFERENCE: PID2020-113943RB-I00.

• Regulación de la señalización temprana del receptor para el antígeno de células T (TCR): relaciones entre los adaptadores de membrana LAT y NTAL y la kinasa Lck e implicaciones en artritis reumatoide. PRINCIPAL INVESTIGATOR: Enrique Aguado Vidal. FUNDING ENTITY/PROGRAM: Consejería de Transformación Económica, Industria, Conocimiento y Universidades. Dirección General de Investigación y Transferencia del Conocimiento. Junta de Andalucía. CENTER: Universidad de Cádiz. REFERENCE: P20_01297.

• Estudio de un mecanismo intrínseco de control de la activación de células T: análisis in vitro e in vivo mediante la generación de un ratón "knockin" para el adaptador LAT como modelo para el análisis de los mecanismos moleculares de tolerancia central. PRINCIPAL INVESTIGATOR: Enrique Aguado Vidal. COLLABORATOR: Miguel Martínez de Arbulo Echevarria (Co-IP). FUNDING ENTITY/PROGRAM: Plan Propio INIBICA. CENTER: INIBICA. REFERENCE: LI19/I14N-CO15.

1. * Enrique Aguado, Ewoud B Compeer, Arkadiusz Miazek. "Editorial: Regulatory Mechanisms of Early Intracellular Signaling in T Lymphocytes". Frontiers in Cell and Developmental Biology, 9: 676949. Impact factor: 6,684. Quartile/Decile: Q1/D2 (6/41 en Developmental Biology, JCR 2020). Cumple con la normativa de filiación del INIBICA.
2. * Vico-Barranco I, Arbulo-Echevarria MM, Serrano-García I, Pérez-Linaza A, Miranda-Sayago JM, Miazek A, Narbona-Sánchez I, Aguado E. "A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling". Cells, 10: 343. Impact factor: 6,600. Quartile/Decile: Q2/D3 (53/195 en Cell Biology, JCR 2020). Cumple con la normativa de filiación del INIBICA.

1. Authors: Arbulo-Echevarria MM, Narbona-Sánchez I, Fernandez-Ponce CM, Vico-Barranco I, Rueda-Ygueravide MD, Dustin ML, Miazek A, Duran-Ruiz MC, García-Cózar F, Aguado E. Title: Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling. Journal: Front Immunol. Year, volume, first and last pages: 2018 Feb 2;9:115. Impact factor: 5. 511. Quartile/Decile in the year of publication: Q1 (30/155 Immunology).
2. Authors: Fernández-Ponce C, Durán-Ruiz MC, Narbona-Sánchez I, MuñozMiranda JP, Arbulo-Echevarria MM, Serna-Sanz A, Baumann C, Litrán R, Aguado E, Bloch W, García-Cozar F. Title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells. Journal: Front Microbiol. Year, volume, first and last pages: 2018 Jan 4;8:2595. doi: 10.3389/fmicb.2017.02595. eCollection 2017. Impact factor: 4.019. Quartile/Decile in the year of publication: Q1 [18 de 80 (Microbiology)].

1. Authors: Vega FM, Gautier V, Fernandez-Ponce CM, Extremera MJ, Altelaar AFM, Millan J, Tellez JC, Hernandez-Campos JA, Conejero R, Bolivar J, Pardal R, García-Cózar FJ, Aguado E, Heck AJR, Duran-Ruiz MC. Title: The atheroma plaque secretome stimulates the mobilization of endothelial progenitor cells ex vivo. Journal: Journal of Molecular and Cellular Cardiology. Year, volume, first and last pages: 2017; 105:12-23. Impact factor: 5,680. Quartile/Decile in the year of publication: Q1.
2. Authors: Fernández-Ponce C, Dominguez-Villar M, Muñoz-Miranda JP, Arbulo-Echevarria MM, Litrán R, Aguado E, García-Cozar F. Title: Immune modulation by the hepatitis C virus core protein. Journal: J Viral Hepat. Year, volume, first and last pages: 2017 May;24(5):350-356. Impact index (IP): 4,122. Quartile/Decile in the year of publication: Q1 (17/84 Infectious Diseases).

1. Authors: Fernandez-Ponce C, Dominguez-Villar M, Enrique Aguado, Francisco J. García-Cózar. Title: CD4+ primary T cells expressing HCV-core protein upregulate FOXP3 and IL-10, suppressing CD4 and CD8 T cells. Journal: PlosOne. Year, volume, first and last pages: 2014 Jan 20;9(1):e85191. Impact index (IP): 3.234 (año 2014). Quartile/Decile in the year of publication: Q1 9/57 de Multidisciplinary Sciences.