{"id":2440,"date":"2023-03-31T13:39:42","date_gmt":"2023-03-31T16:39:42","guid":{"rendered":"https:\/\/ibyme.org.ar\/investigacion\/?page_id=2440"},"modified":"2023-07-11T15:26:44","modified_gmt":"2023-07-11T18:26:44","slug":"lineas-de-investigacion-endocrinologia","status":"publish","type":"page","link":"https:\/\/ibyme.org.ar\/investigacion\/laboratorios\/receptores-nucleares\/lineas-de-investigacion-endocrinologia\/","title":{"rendered":"L\u00edneas de Investigaci\u00f3n: Endocrinolog\u00eda"},"content":{"rendered":"<p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background fusion-parallax-none hundred-percent-fullwidth non-hundred-percent-height-scrolling\" 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fusion-content-layout-column\"><nav class=\"fusion-breadcrumbs awb-yoast-breadcrumbs fusion-breadcrumbs-1\" style=\"--awb-alignment:left;--awb-breadcrumb-sep:&#039;\/&#039;;text-align:left;\" aria-label=\"Breadcrumb\"><span><span><a href=\"https:\/\/ibyme.org.ar\/investigacion\/en\/laboratories\/\">Inicio<\/a><\/span><\/span><\/nav><div class=\"fusion-title title fusion-title-1 fusion-sep-none fusion-title-text fusion-title-size-one\" style=\"--awb-text-color:var(--awb-color8);\"><h1 class=\"fusion-title-heading title-heading-left\" style=\"margin:0;\">Receptores Nucleares<\/h1><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-4 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-title title fusion-title-2 fusion-sep-none fusion-title-text fusion-title-size-two\" style=\"--awb-text-color:var(--awb-color5);--awb-font-size:22px;\"><h2 class=\"fusion-title-heading title-heading-left\" style=\"font-family:&quot;Red Hat Display&quot;;font-style:normal;font-weight:700;margin:0;font-size:1em;\">L\u00edneas de Investigaci\u00f3n: Endocrinolog\u00eda<\/h2><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-5 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\"><p>Si pudi\u00e9ramos manipular con drogas los mecanismos que regulan la localizaci\u00f3n subcelular de factores de transcripci\u00f3n claves para el ciclo de vida de la c\u00e9lula, podr\u00edamos influir sobre los mismos seg\u00fan sea necesario y conveniente. Por ejemplo, el factor transcipcional NF\u03baB muestra una persistente localizaci\u00f3n nuclear en un alto porcentaje de tumores, en otros, p53 se excluye del n\u00facleo afectando los mecanismos de defensa proapopt\u00f3ticos. Resultar\u00eda provechoso desde el punto de vista terap\u00e9utico revertir tales desbalances en la distribuci\u00f3n subcelular de estas prote\u00ednas en c\u00e9lulas tumorales. Nuestro equipo estudia la participaci\u00f3n de inmunofilinas de alto peso molecular en el mecanismo de transporte y anclado a estructuras celulares de variados factores nucleares.<br \/>\nLas inmunofilinas son prote\u00ednas que poseen un dominio con actividad enzim\u00e1tica de peptidil-prolil isomerasa, el cual tambi\u00e9n une drogas inmunosupresoras. S\u00f3lo las inmunofilinas de menor peso molecular (FKBP12 y CyP17) poseen efecto inmunosupresor al unir la droga, pero no es \u00e9ste el caso para el resto de los miembros de la familia (FKBP52, FKBP51, FKBP38, CyP40, PP5, etc.). Las de mayor tama\u00f1o se expresan en abundancia y poseen caracter\u00edsticas de chaperonas moleculares, pero debido a que reci\u00e9n fueron descubiertos hacen pocos a\u00f1os atr\u00e1s, sus propiedades biol\u00f3gicas son poco conocidas. Recientemente, demostramos que el complejo FKBP52\u2022Hsp90 es requerido para que los receptores esteroidales interact\u00faen con el complejo motor de dine\u00edna\/dinactina, lo que favorece as\u00ed su transporte al n\u00facleo en presencia de la hormona. A ese modelo lo extendimos luego a otros factores nucleares tales como NF\u03baB, hTERT, AP1, HSF-1 y p53. Los hallazgos sugieren que la regulaci\u00f3n del transporte y localizaci\u00f3n final de factores nucleares afecta a prote\u00ednas de variada naturaleza y est\u00e1n sujetos al tipo de est\u00edmulo.<br \/>\nLas inmunofilinas tambi\u00e9n se concentran en el n\u00facleo y act\u00faan como moduladores transcripcionales. As\u00ed, FKBP51 posee efecto inhibitorio y FKBP52 es estimulatorio o neutro, dependiendo del tipo celular. En el laboratorio estudiamos si estas prote\u00ednas participan en la organizaci\u00f3n estructural de la cromatina en los sitios donde la maquinaria transcripcional traduce la informaci\u00f3n codificada en los genes-blanco. La evidencia sugiere que FKBP52 ser\u00eda un factor de retenci\u00f3n nuclear del receptor de glucocorticoides (GR) facilitando su anclado a la cromatina, mientras que FKBP51 favorecer\u00eda su exclusi\u00f3n nuclear. Nuestro modelo propone que el balance de expresi\u00f3n diferencial entre ambas inmunofilinas es uno de los factores que regular\u00eda el pleiotropismo funcional de GR en diferentes tejidos. Resultados similares permiten aplicar tal modelo a NF-kB.<br \/>\nDemostramos que FKBP51 tambi\u00e9n es una prote\u00edna mitocondrial que migra de manera r\u00e1pida y reversible al n\u00facleo seg\u00fan el est\u00edmulo. Ello nos llev\u00f3 a estudiar el efecto de FKBP51 sobre la apoptosis, y demostramos su acci\u00f3n antiapopt\u00f3tica. Al inhibir la muerte celular, era probable que FKBP51 participara en procesos tumorales, lo que nos llev\u00f3 a estudiar las propiedades de FKBP51 en variados tipos celulares tumorales y en biopsias normales y patol\u00f3gicas. Los resultados indican que FKBP51 es efectivamente un nuevo factor pro-tumoral. Demostramos que controla el ciclo de vida y muerte celular, y que es un factor esencial para mantener la estructura cromos\u00f3mica luego de cada divisi\u00f3n de la c\u00e9lula estimulando la actividad de la transcriptasa reversa de la telomerasa (TERT).<br \/>\nNuestro grupo tambi\u00e9n estudia la capacidad de las chaperonas moleculares de regular la diferenciaci\u00f3n neuronal a partir de c\u00e9lulas embrionarias parcial o totalmente indiferenciadas, as\u00ed como de participar en el proceso de transdiferenciaci\u00f3n, es decir, la reprogramaci\u00f3n de c\u00e9lulas comprometidas con un cierto linaje hacia otro diferente. Los estudios abarcan desde los cambios fenot\u00edpicos de las c\u00e9lulas en cultivo, los cambios asociados a la estructura nuclear y a la arquitectura del citoesqueleto, hasta los efectos in vivo en modelos animales en donde las immunofilinas son utilizadas como blancos farmacol\u00f3gicos para la neurorregeneraci\u00f3n y la neuroprotecci\u00f3n.<br \/>\nEn el laboratorio tambi\u00e9n se realizan estudios relacionados con la capacidad de los receptores esteroidales de reconocer a esteroides que posean ciertas propiedades conformacionales y de gatillar determinados efectos biol\u00f3gicos. Los estudios se focalizan fundamentalmente (pero no exclusivamente) en la funci\u00f3n glucocorticoide y mineralocorticoide, y comprenden desde los cl\u00e1sicos experimentos funcionales in vivo hasta el an\u00e1lisis de las propiedades moleculares del mecanismo de acci\u00f3n del complejo hormona-receptor.<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":41,"featured_media":0,"parent":2437,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"100-width.php","meta":{"_acf_changed":false,"inline_featured_image":false,"wpupg_custom_link":[],"wpupg_custom_link_behaviour":["default"],"wpupg_custom_link_nofollow":[],"wpupg_custom_image":[],"wpupg_custom_image_id":[],"footnotes":""},"page_category":[],"class_list":["post-2440","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>L\u00edneas de Investigaci\u00f3n: Endocrinolog\u00eda - 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