Molecular Pathology/ Complement Genetics

Our laboratory uses genomics and molecular biology techniques to carry out research in Human Genetics. Overall, there is a strong -long standing- interest in Complement genetics. Since 1983, our laboratory has been involved in the study of the genetics and function of the proteins that regulate the complement system. We described in 1986 the human "Regulators of Complement Activation" (RCA) gene cluster in chromosome 1q32 and subsequently provided most of our current understanding of the genomic organization of this region of the human genome. Recent work in this area has focussed on the study of the role of RCA proteins in susceptibility to renal and ocular disorders.

Additional contributions of our laboratory to the field of Human Genetics include: The cloning of the gene responsible for alkaptonuria (AKU) and the complete characterization of the molecular, structural and epidemiological basis of this disease; The cloning of the human homeobox gene SIX6 as a gene responsible for anophtalmia and pituitary anomalies; The cloning of the genes MCCA and MCCB responsible for the 3-methylcrotonyglycinuria; and the molecular cloning of one of the genes responsible for the lethal progressive myoclonous epilepsy called Lafora´s disease.

Over the last few years the study of the molecular bases of Lafora’s disease has been one of our major areas of research activity. In addition, we are interested in DNA sequencing and its applications in genomic and genetic research. In collaboration with Secugen SL, a biotechnological company interested in DNA sequencing and molecular diagnostic, we have developed approaches to characterize the human mitochondrial genome and to perform the molecular diagnosis of various human diseases.

► Video in The Biomedical and Life Sciences Collection : Rodríguez de Córdoba, S. (2018, June 28). Physiopathological implications of genetic variability in the complement alternative pathway. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved July 10, 2018, from https://hstalks.com/bs/3765/.

Staff Scientists
Santiago Rodríguez de Cordoba

Technician
Andrea Reparaz Suevos
Lucia Juana Lopez

Predoctoral Students
Silvia González Sanz

Visitors
Ángela Olimpia Ruiz Sánchez
Sheila Pinto García
Elena Isabel Goicoechea de Jorge
Barbara Marquez Tirado
Alejandro Chozas Hernández

Serrano, I., Luque, A., Ruiz-Cerulla, A., Navas, S., Blom, A.M., Rodríguez de Córdoba, S., Fernández, F.J., Cristina Vega, M., Rodríguez-Moranta, F., Guardiola, J., Aran, J.M. [2023]. C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients. Pharmacological Research. 197:doi: /10.1016/j.phrs.2023.106948..

Huerta, A., Arjona, E., Portoles, J., Lopez-Sanchez, P., Cavero, T., Fernandez-Cusicanqui, J., Blasco, M., Cabello, V., Calvo, N., Diaz, M., Herrero-Goñi, M., Aguirre, M., Elías, S., Alcaide, M.P., Ramos, N., Sellares, J., Rodríguez de Córdoba, S. [2023]. On the relevance of thrombomodulin variants in atypical hemolytic uremic syndrome. Kidney International. 104:851-855.

Navas-Yuste, S., de la Paz, K., Querol-García, J., Gómez-Quevedo, S., Rodríguez de Córdoba, S., Fernández, F.J., Vega, M.C. [2023]. The structure of Leptospira interrogans GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity. Frontiers in Immunology. 14:1190943. doi: 10.3389/fimmu.2023.1190943.

Caravaca-Fontán, F., Cavero, T., Díaz-Encarnación, M., Cabello, V., Ariceta, G., Quintana, L.F., Marco, H., Barros, X., Ramos, N., Rodríguez-Mendiola, N., Cruz, S., Fernández-Juárez, G., Rodríguez, A., Pérez De José, A., Rabasco, C., Rodado, R., Fernández, L., Pérez-Gómez, V., Ávila, A., Bravo, L., Espinosa, N., Allende, N., Sanchez De La Nieta, M.D., Rodríguez, E., Rivas, B., Melgosa, M., Huerta, A., Miquel, R., Mon, C., Fraga, G., De Lorenzo, A., Draibe, J., González, F., Shabaka, A., López-Rubio, M.E., Fenollosa, M.Á., Martín-Penagos, L., Da Silva, I., Titos, J.A., Rodríguez De Córdoba, S., Goicoechea De Jorge, E., Praga, M. [2023]. Clinical Profiles and Patterns of Kidney Disease Progression in C3 Glomerulopathy. Kidney360. 4:659-672.

Giang, J., van Doorn, M.B.A., Diercks, G.F.H., de Cordoba, S.R., van den Bosch, T.P.P., Schreurs, M.W.J., Poppelaars, F., Damman, J. [2023]. Successful pharmacological intervention at different levels of the complement system in an in vitro complement fixation model for bullous pemphigoid. Experimental Dermatology. 32:632-640.

Okrój, M., Rodriguez de Córdoba, S. [2023]. Will a hyperactive classical complement pathway exacerbate autoimmune diseases?. Autoimmunity Reviews. 22:103241. doi: 10.1016/j.autrev.2022.103241.

Rodríguez de Córdoba, S. [2023]. Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases. Immunological Reviews. 313:71-90.

Cavero, T., Auñón, P., Caravaca-Fontán, F., Trujillo, H., Arjona, E., Morales, E., Guillén, E., Blasco, M., Rabasco, C., Espinosa, M., Blanco, M., Rodríguez-Magariños, C., Cao, M., Ávila, A., Huerta, A., Rubio, E., Cabello, V., Barros, X., Goicoechea De Jorge, E., Rodríguez De Córdoba, S., Praga, M. [2023]. Thrombotic microangiopathy in patients with malignant hypertension. Nephrology Dialysis Transplantation. 38:1217-1226.

Kuźniewska, A., Thiel, M., Kowalska, D., Felberg-Miętka, A., Szynkowski, P., Ołdziej, S., Arjona, E., Jongerius, I., Rodriguez de Córdoba, S., Okrój, M., Urban, A. [2022]. Substitutions at position 263 within the von Willebrand factor type A domain determine the functionality of complement C2 protein. Frontiers in Immunology. 13:1061696. doi: 10.3389/fimmu.2022.1061696.

Caravaca-Fontán, F., Rivero, M., Cavero, T., Díaz-Encarnación, M., Cabello, V., Ariceta, G., Quintana, L.F., Marco, H., Barros, X., Ramos, N., Rodríguez-Mendiola, N., Cruz, S., Fernández-Juárez, G., Rodríguez, A., De José, A.P., Rabasco, C., Rodado, R., Fernández, L., PCrossed D Sign©rez-Gómez, V., Ávila, A., Bravo, L., Espinosa, N., Allende, N., De La Nieta, M.D.S., Rodríguez, E., Olea, T., Melgosa, M., Huerta, A., Miquel, R., Mon, C., Fraga, G., De Lorenzo, A., Draibe, J., González, F., Shabaka, A., López-Rubio, M.E., Fenollosa, M.Á., Martín-Penagos, L., Da Silva, I., Alonso Titos, J., De Córdoba, S.R., De Jorge, E.G., Praga, M. [2022]. Development and validation of a nomogram to predict kidney survival at baseline in patients with C3 glomerulopathy. Clinical Kidney Journal. 15:1737-1746.

All Publications

CURRENT PROJECTS:

Papel de las proteínas relacionadas con FH en la regulación del Complemento y nuevos modelos de ratón de desregulación del Complemento (Ref. PID2019-104912RB-I00)
MICINN, Programa Retos Investigación
01/06/2020 - 31/05/2023

El Sistema del Complemento en Salud y Enfermedad. (Ref. S2022/BMD-7278 - Acrónimo: COMPLEMENTO III-CM)
Ayudas para la realización de Programas de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid en Biomedicina.
01/01/2023 - 31/12/2024
Convocatoria cofinanciada por el Fondo Social Europeo y el Fondo Europeo de Desarrollo Regional, 2022, de la Comunidad de Madrid.

Complemento en Salud y Enfermedad (Ref. RED2022-134750-T)
MICINN
01/01/2023 - 31/12/2024

FINISHED PROYECTS:

El Sistema del Complemento en Salud y Enfermedad. (Ref. S2017/BMD-3673 - Acrónimo: COMPLEMENTO II-CM)
Ayudas para la realización de Programas de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid en Biomedicina.
01/01/2018 - 31/12/2021
Convocatoria cofinanciada por el Fondo Social Europeo y el Fondo Europeo de Desarrollo Regional, 2014-2020, de la Comunidad de Madrid.

Modeling C3-Glomerulopathy risk factor in mice (Ref. OPE01750)
Fundación Kidneeds
01/01/2019 - 31/12/2020 (Prórroga hasta el 01/02/2021)

Descifrando las bases moleculares de las enfermedades relacionadas con desregulación del complemento y aprendiendo como tratarlas (Ref. SAF2015-66287-R)
MINECO/FEDER, Programa RETOS
01/01/2016 - 31/12/2019 (Prórroga hasta 31/12/2020)
Convocatoria cofinanciada por el Fondo Europeo de Desarrollo Regional (FEDER)

Complemento en Salud y Enfermedad (Ref. SAF2016-81876-REDT)
Agencia Estatal de Investigación (AEI), Programa REDES DE EXCELENCIA
01/07/2017 - 30/06/2019 (Prórroga hasta el 31/12/2019)

Plataforma integrada para el diagnóstico molecular de enfermedades relacionadas con el sistema del complemento. PIDMECOMP (Ref. RTC-2016-4635-1)
MINECO/FEDER, Programa RETOS-COLABORACION
04/03/2016 - 31/12/2018 (Prórroga hasta el 30/06/2019)
Convocatoria cofinanciada por la Unión Europea, Fondo Europeo de Desarrollo Regional (FEDER)

Desarrollo de un Centro de Referencia para patologías raras asociadas a desregulación del sistema del complemento.
Fundación Inocente Inocente
01/01/2018 - 31/12/2018

EURenOmics - European Consortium for High-Throughput Research in Rare Kidney Diseases (Ref. 305608 / Acronym: EURenOmics)
FP7-HEALTH-2012-INNOVATION-1, COLABORATIVE PROJECT
01/10/2012 - 30/09/2017

Mecanismos patogénicos en enfermedades raras y comunes asociadas con desregulación del complemento (Ref. ER16P1AC738)
CIBERER, ACCI2015
01/01/2016 - 31/03/2017

Complemento y Enfermedad (Ref. SAF-2011-26583)
MINECO
01/01/2012 - 31/12/2015

Biología y fisiopatología del sistema del complemento (Ref. S2010/BMD-2316)
CAM, Convocatoria BIOMEDICINA
01/01/2012 - 31/12/2015
Convocatoria cofinanciada por el Fondo Social Europeo y del Fondo Europeo de Desarrollo Regional (FEDER)

► Video in The Biomedical and Life Sciences Collection : Rodríguez de Córdoba, S. (2018, June 28). Physiopathological implications of genetic variability in the complement alternative pathway. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved July 10, 2018, from https://hstalks.com/bs/3765/.

Group Leader/s

Santiago Rodríguez de Cordoba

intro

Research lines

Complement genes and predisposition to disease

Molecular bases of the progressive myoclonous epilepsy of the Lafora type.

Developmental genes and human disease.

DNA sequencing and mitochondrial genomics.

Molecular basis of Alkaptonuria and other metabolic disorders.

Members

Selected Publications

Okrój, M., Rodriguez de Córdoba, S. [2023]. Will a hyperactive classical complement pathway exacerbate autoimmune diseases?. Autoimmunity Reviews. 22:103241. doi: 10.1016/j.autrev.2022.103241.

Rodríguez de Córdoba, S. [2023]. Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases. Immunological Reviews. 313:71-90.

Funding

More info