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Expresión Y Función De Los Factores De Transcripción Foxe1 Y Sox9 En La Célula Folicular Tiroidea

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Expresión Y Función De Los Factores De Transcripción Foxe1 Y Sox9 En La Célula Folicular Tiroidea UNIVERSIDAD AUTÓNOMA DE MADRID DEPARTAMENTO DE BIOQUÍMICA EXPRESIÓN Y FUNCIÓN DE LOS FACTORES DE TRANSCRIPCIÓN FOXE1 Y SOX9 EN LA CÉLULA FOLICULAR TIROIDEA TESIS DOCTORAL ARÍSTIDES LÓPEZ MÁRQUEZ MADRID, 2017 Departamento de Bioquímica Facultad de Medicina Universidad Autónoma de Madrid Expresión y función de los factores de transcripción FoxE1 y Sox9 en la célula folicular tiroidea Memoria de Tesis Doctoral presentada por: Arístides López Márquez Licenciado en Bioquímica Para optar al grado de Doctor por la Universidad Autónoma de Madrid Directora de Tesis: Dra. Pilar Santisteban Sanz Profesora de Investigación del CSIC Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM Madrid, 2017 Pilar Santisteban Sanz, Doctora en Biología y Profesora de Investigación del Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, CERTIFICA QUE: Arístides López Márquez, Licenciado en Bioquímica por la Universidad Autónoma de Madrid, ha realizado, bajo mi dirección, el trabajo: “Expresión y función de los factores de transcripción FoxE1 y Sox9 en la célula folicular tiroidea” En esta memoria de tesis doctoral se ha estudiado la regulación de la expresión por TSH y TGFβ de los factores de transcripción FoxE1 y Sox9 en la diferenciación de las células foliculares tiroideas. Mediante análisis in sílico y ensayos funcionales se ha descrito la existencia de una intercomunicación cruzada entre las vías de cAMP/PKA y las proteínas Smads. Asimismo se ha descrito la participación de otros factores de transcripción como Nkx2-1 y Pax8 en ese circuito regulatorio del control de la diferenciación tiroidea. Para llevar a cabo este trabajo se han usado como modelos cultivos celulares, células madre embrionarias (mESC), células foliculares de tiroides de rata y ratón embrionario y adulto. El trabajo realizado por el doctorando ha sido de gran calidad demostrando su responsabilidad científica, su dedicación al trabajo y el juicio crítico necesario en la búsqueda de nuevos conocimientos científicos. Considero por tanto este trabajo satisfactorio y apto para ser presentado como tesis doctoral en el Departamento de Bioquímica de la Universidad Autónoma de Madrid. Y para que conste a los efectos oportunos, expido el presente certificado en Madrid a 5 de mayo de 2017. Fdo. Pilar Santisteban Sanz Este trabajo ha sido realizado en el laboratorio de la profesora Pilar Santisteban Sanz en el Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), financiado por una Beca de Formación de Personal Investigador (FPI) de la Universidad Autónoma de Madrid. “Tratad de dejar este mundo en mejores condiciones de cómo os lo encontrasteis” Último mensaje de Sir Lord Robert S. Smith Baden-Powell of Gilwell, Fundador del Movimiento Scout y primer Jefe Scout Mundial A mis padres, Rosario y Arístides A mis abuelas, Lalo y María AGRADECIMIENTOS Esta tesis no podría haber salido adelante sin el trabajo, apoyo y ayuda de una lista enorme de gente, por lo que mis agradecimientos no pueden dejar de ser numerosos y sinceros. Escribo estas líneas en un tren en algún punto entre Madrid y Sanlúcar. Estos agradecimientos estarán también repartidos entre estos dos lugares, aunque con algunas paradas intermedias. En primer lugar debo, y quiero, dar las gracias a Pilar, mi directora de tesis, La Jefa. Me da la sensación de que las palabras “gracias” y “agradecimientos” se quedan cortas para todo lo que me gustaría expresar en estas pocas líneas. En primer lugar gracias por, hace ya más de 6 años, haberme hecho aquella entrevista en la que casi hablamos más de Manzanilla y en que bares encontrarla en Madrid que de tiroides. Salí de ese despacho y de ese laboratorio convencido de que era ahí donde quería hacer mi tesis doctoral. Gracias por tu apoyo, tus ánimos, tus gritos y tu sentido del humor. Gracias por tantas risas. Gracias por enseñarme a hacer ciencia de calidad y por tener esa memoria privilegiada capaz de recordar autores, año, revista y título de cada publicación de tiroides. Gracias por haberme dado la oportunidad de trabajar en tu laboratorio y apoyarme y financiarme cuando parecía imposible conseguir una beca de doctorado. Siempre me sentí respaldado para poder seguir intentándolo. No sabes que importante fue aquello para mí. Gracias por ser una de las personas más “jóvenes” que conozco y hacer que sea tan fácil y tan divertido hablar de ciencia, de bares, de viajes, o de todo a la vez. Gracias por crear ese ambiente de trabajo tan familiar y tan cómodo que creas en tu laboratorio. Los que aquí nos hemos “criado” creo que no valoramos lo suficiente el lujo que es trabajar así. Gracias por tantísimos guateques, por tantas cenas en tu casa, por tantos momentos que no olvidaré jamás. Gracias por enseñarme, en definitiva, a ser un buen científico pero a la vez disfrutar de la buena mesa y el buen vino, es decir, de la buena vida. Gracias Pilar. Y Pilar no sería Pilar sin Edu, el jefe consorte. Gracias, en primer lugar, por ser tan generoso y por apoyar, ayudar y acompañar desde hace tantos años a la jefa. Esto es fundamental, más de lo que crees, para Pilar, para nosotros y para el laboratorio, que no sería lo mismo sin ti. Gracias por ser como eres, por tu fuerza, por tus ganas de disfrutar de la vida; y, venga, también por tus chistes. Gracias por tus consejos sobre bares de Madrid, España y parte del extranjero. Gracias por cocinar como cocinas, por esas croquetas y aquel botillo. Y gracias por preparar los mejores gin tonics que he probado en mi vida. Edu, de corazón, gracias por tu amistad y tu cariño. La ciencia es un trabajo en equipo, por lo que esta tesis no habría salido adelante sin todas las personas que en estos años han pasado por el 2.9. Gracias Ana, por enseñarme todo lo que debía saber y enseñarme a “volar solo” en un laboratorio. Gracias por tener tanta paciencia para ponerte conmigo a hacer un western, cultivos o mi primera PCR. Fuiste mi “subjefa” y así te veré siempre. Y hablando de históricos del 2.9, hay que seguir con Miguel, sin el que el 2.9 no sería el 2.9. Muchas gracias Miguel por tu apoyo, tus conversaciones y tus consejos. Gracias por saber tantísimo de tiroides y de vías de señalización. Eres fundamental en este laboratorio. Garci, muchas gracias por ser tan buena persona, por tus consejos siempre tan sinceros y por tener ese ánimo de ayudar en todo momento. Gracias por soportar mis coñas con tu ropa, sabes que son desde el cariño, a pesar de que nunca me traes cecina de León. Corrección: Al final trajiste, eres un campeón. Antonio, muchas gracias por enseñarme la importancia de un control de carga y por los buenos ratos que hemos pasado. Lara, muchas gracias por tus risas, nuestras conversaciones extra científicas, por haberme enseñado a explorar los promotores de los genes y por haberme hecho tan fácil trabajar contigo. No se me olvidará aquel mes de agosto revisando los comentarios de los referees de la review. Petri, muchas gracias por nuestras charlas de última hora ya de noche en el labo, por tu seriedad, tu profesionalidad y tu cariño. Espero que en esta nueva etapa que empiezas seas muy feliz. Gracias León, por tu vitalidad, por los ratos que hemos compartido en tantos congresos y por ser tan entusiasta. Seguro que el futuro te tiene preparadas grandes cosas. Jesús, gracias por ser un compañero de “pupitre” tan respetuoso y tranquilo, pudiendo haber escrito esta tesis casi sin bajar a los infiernos de la biblioteca. Ha sido un auténtico placer compartir contigo estos años, y los que vengan. Y gracias a las nuevas generaciones: Adri, gracias por estar siempre dispuesto a echarme una mano, bien con una inmunohistoquímica o con el dichoso Excel. Eres un tío brillante. Vente a vivir a Madrid ya. Celia, muchas gracias por hacer que me ría tanto. Eres la persona más divertida que he conocido dentro del 2.9, con diferencia. Julia, eres la promesa del laboratorio. Una trabajadora y una científica genial. Seguro que todo lo que queda por venir, que es mucho, será increíble. Carlos, el mejor “pupilo” que me pudo tocar. Gracias por ser tan responsable, tan divertido, tan buena gente y tan trabajador. Ha sido un placer trabajar contigo. Espero que lo siga siendo en el futuro y que nos sigan tocando cestas de lo que sea, a poder ser de ibéricos en lugar de frutas. Y Andrea, nuestra sargento del 2.9. Gracias por tus broncas, tus enfados y tus quejas. Sirven para que el laboratorio esté todo en orden. Pero gracias también por tu amabilidad y tu inocencia. Gracias a todos por haber dado un soplo de aire fresco al laboratorio y por haberos acoplado a este ecosistema un tanto peculiar que tenemos en el 2.9. Ya fuera del 2.9 he conocido gente maravillosa en el IIB. Me gustaría agradecer en particular a Elvira, la mejor compañera de congresos, confidencias, y conversaciones sobre la vida y la ciencia. Gracias por todos esos ratos de “vidorra” que hemos disfrutado juntos, que sean muchos más. Y aunque sea del IIB y del 2.9, mención aparte merece Suzana. Desde el primer día me regalaste tu amistad. Gracias por mostrarme la otra cara de la ciencia, por tantos vinos, por enseñarme Madrid. Gracias por tantos viajes y tantos buenos ratos. Gracias por Brasil. Gracias por ser tan valiente y ser una luchadora y una superviviente. Gracias por ser enfermizamente buena y por tener ese carácter tan tuyo. Nos quedan muchos vinos que tomarnos, en Granada, en Madrid o en el mundo. Gracias por estar ahí. Toca agradecer a la gente con la que he recorrido este camino paso a paso y en paralelo.
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