THE WILMS TUMOR SUPPRESSOR GENE (WT1). REGULATION OF ITS EXPRESSION AND INVOLVEMENT IN DEVELOPMENT PROCESSES, ADULT HOMEOSTASIS AND PATOPHYSIOLOGY (Q3134594)
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Project Q3134594 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | THE WILMS TUMOR SUPPRESSOR GENE (WT1). REGULATION OF ITS EXPRESSION AND INVOLVEMENT IN DEVELOPMENT PROCESSES, ADULT HOMEOSTASIS AND PATOPHYSIOLOGY |
Project Q3134594 in Spain |
Statements
135,520.0 Euro
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169,400.0 Euro
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80.0 percent
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1 January 2015
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31 October 2018
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UNIVERSIDAD DE MALAGA
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36°43'16.68"N, 4°25'17.90"W
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29067
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EL GEN SUPRESOR DEL TUMOR DE WILMS (WT1) SE HA CONVERTIDO EN LOS ULTIMOS AÑOS EN CENTRO DE ATENCION DE NUMEROSOS GRUPOS DE INVESTIGACION POR SUS IMPLICACIONES EN DESARROLLO, HOMEOSTASIS Y PATOLOGIAS HUMANAS, PARTICULARMENTE EN CANCER. ACTUALMENTE WT1 ES CONSIDERADO COMO LA MOLECULA MAS PROMETEDORA EN ENSAYOS DE INMUNOTERAPIA CONTRA EL CANCER. EN LA CONVOCATORIA 2011 SE NOS CONCEDIO UN PROYECTO DE INVESTIGACION SOBRE DISTINTOS ASPECTOS DE LA FUNCION DE WT1 EN EL DESARROLLO EMBRIONARIO. ESTE PROYECTO DIO LUGAR A UN NUMERO IMPORTANTE DE PUBLICACIONES DE BUEN NIVEL, Y AL MISMO TIEMPO DEJO ABIERTAS UNA SERIE DE CUESTIONES QUE CONSIDERAMOS DE GRAN INTERES Y CUYO ABORDAJE PLANTEAMOS AQUI CON UN GRUPO DE INVESTIGACION MAS AMPLIO Y MAS INTERDISCIPLINAR. SON TEMAS QUE PARTEN DE NUESTRA EXPERIENCIA PREVIA, SUSTENTADA POR RESULTADOS PRELIMINARES Y QUE SERAN ABORDADOS POR UN EQUIPO DE TRABAJO INTERNACIONAL CONSTITUIDO GRACIAS A LAS RELACIONES QUE HEMOS ESTABLECIDO EN LOS ULTIMOS AÑOS (OCHO DOCTORES Y UNA LICENCIADA EN TOTAL). EN CONCRETO PLANTEAMOS ESTUDIAR:_x000D_ 1) LA REGULACION POSITIVA Y NEGATIVA DE LA EXPRESION DE WT1 POR ACIDO RETINOICO Y POR LA VIA CALCINEURINA/NFATC1, RESPECTIVAMENTE. ESTA ULTIMA VIA, EN CASO DE SER CONFIRMADA, PROPORCIONARIA LA PRIMERA EVIDENCIA CONOCIDA DE UN PROCESO FISIOLOGICO DE SILENCIAMIENTO DE WT1 DURANTE EL DESARROLLO._x000D_ 2) LA IMPLICACION DE WT1 EN DESARROLLO NEURAL. ESTE ES UN ASPECTO DE LA FUNCION DE WT1 QUE NO HA SIDO CONVENIENTEMENTE TRATADO, Y A CUYO CONOCIMIENTO PODEMOS APORTAR IMPORTANTES NOVEDADES A PARTIR DE LOS MODELOS ANIMALES CON LOS QUE CONTAMOS._x000D_ 3) LA IMPLICACION DE WT1 EN ANGIOGENESIS TUMORAL Y ERITROPOYESIS ADULTA. SABEMOS QUE WT1 NO DESEMPEÑA NINGUN PAPEL IMPORTANTE EN ANGIOGENESIS FISIOLOGICA PERO PODRIA SER EXPRESADO Y TAL VEZ INCLUSO REQUERIDO PARA LA ANGIOGENESIS TUMORAL. ESTO MARCARIA UNA DIFERENCIA ESENCIAL ENTRE LOS DOS TIPOS DE ANGIOGENESIS, Y PODRIA PROPORCIONAR NUEVAS DIANAS ANTIANGIOGENICAS EN EL TRATAMIENTO DEL CANCER. POR OTRO LADO, TENEMOS RAZONES PARA PENSAR QUE WT1 DESEMPEÑA UN PAPEL CLAVE EN LA ERITROPOYESIS ADULTA, PROBABLEMENTE ACTIVANDO LA EXPRESION DEL RECEPTOR DE ERITROPOYETINA. DE HECHO, LA ERITROPENIA ES UNA LLAMATIVA CONSECUENCIA DEL SILENCIAMIENTO SISTEMICO DE WT1 EN EL RATON ADULTO._x000D_ 4) LA IMPLICACION DE WT1 EN LA HOMEOSTASIS DEL CORAZON ADULTO, Y LAS CONSECUENCIAS DE SU SILENCIAMIENTO EN UN MODELO ANIMAL SIMILAR AL HUMANO. HASTA LA FECHA NO SE HAN ESTUDIADO LAS CONSECUENCIAS DE UN SILENCIAMIENTO CARDIO-ESPECIFICO DE WT1 EN ORGANISMOS ADULTOS, AUNQUE SE SABE QUE EL SILENCIAMIENTO SISTEMICO EN EL RATON ADULTO PROVOCA UNA RAPIDA PERDIDA DE MASA CARDIACA. _x000D_ CREEMOS QUE PARA ALCANZAR ESTOS OBJETIVOS CONTAMOS CON UN BUEN EQUIPO DE TRABAJO CON INVESTIGADORES RESIDENTES EN VARIOS PAISES, CON LOS QUE YA HEMOS COLABORADO PREVIAMENTE Y QUE CUENTAN CON PUBLICACIONES CONJUNTAS CON NOSOTROS. CONTAMOS ADEMAS CON LA PRACTICA TOTALIDAD DE LOS MODELOS DE RATON TRANSGENICO DISPONIBLES PARA ESTUDIOS RELACIONADOS CON EL GEN WT1._x000D_ EN RESUMEN, CREEMOS QUE SE TRATA DE UN PROYECTO CON UNA ALTA CAPACIDAD DE GENERACION DE CONOCIMIENTO Y RESULTADOS PUBLICABLES A UN ALTO NIVEL, QUE SERA REALIZADO POR UN EQUIPO DE TRABAJO QUE REUNE UNA ENORME EXPERIENCIA, Y CUYOS RESULTADOS PODRIAN TENER APLICACIONES REALES EN EL CAMPO DE LA CLINICA. (Spanish)
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THE WILMS TUMOR SUPPRESSOR GENE (WT1) HAS BECOME THE FOCUS OF MANY RESEARCH GROUPS FOR ITS DEVELOPMENTAL IMPLICATIONS, HOMEOSTASIS AND HUMAN PATHOLOGIES, PARTICULARLY IN CANCER. WT1 IS CURRENTLY CONSIDERED THE MOST PROMISING MOLECULATE IN IMMUNOTHERAPY TRIALS AGAINST CANCER. IN THE 2011 CALL WE WERE GRANTED A RESEARCH PROJECT ON DIFFERENT ASPECTS OF WT1'S ROLE IN EMBRYONIC DEVELOPMENT. THIS PROJECT LED TO AN IMPORTANT NUMBER OF PUBLICATIONS OF GOOD LEVEL, AND AT THE SAME TIME LEFT OPEN A SERIES OF QUESTIONS THAT WE CONSIDER OF GREAT INTEREST AND WHOSE APPROACH WE RAISE HERE WITH A BROADER AND MORE INTERDISCIPLINARY RESEARCH GROUP. THESE ARE TOPICS THAT START FROM OUR PREVIOUS EXPERIENCE, SUPPORTED BY PRELIMINARY RESULTS AND WILL BE ADDRESSED BY AN INTERNATIONAL TEAM FORMED THANKS TO THE RELATIONSHIPS THAT WE HAVE ESTABLISHED IN THE LAST YEARS (EIGHT DOCTORS AND ONE GRADUATE IN TOTAL). In CONCRETE we are studying:_x000D_ 1) POSITIVE AND NEGATIVE REGULATION OF WT1 EXPRESSION FOR RETINOIC ACIDO AND FOR THE VIA CALCINEURINA/NFATC1, RESPECTIVELY. This LAST VIA, in case of being confirmed, would provide the first known EVIDENCE OF a physiological process of WT1 SILENTING DURING DEVELOPMENT._x000D_ 2) THE IMPLICATION OF WT1 IN NEURAL DEVELOPMENT. This is an aspect of WT1‘s function that has not been properly treated, and when we know we can carry important new ones to take part in the ANIMAL models we are dealing with._x000D_ 3) WT1’s IMPLICATION IN TUMORAL ANGIOGENESIS AND ADULT ERITROPOYESIS. WE KNOW THAT WT1 DOES NOT PLAY ANY IMPORTANT ROLE IN PHYSIOLOGICAL ANGIOGENESIS BUT COULD BE EXPRESSED AND PERHAPS EVEN REQUIRED FOR TUMOR ANGIOGENESIS. THIS WOULD MAKE AN ESSENTIAL DIFFERENCE BETWEEN THE TWO TYPES OF ANGIOGENESIS, AND COULD PROVIDE NEW TARGETS FOR CANCER TREATMENT. ON THE OTHER HAND, WE HAVE REASON TO BELIEVE THAT WT1 PLAYS A KEY ROLE IN ADULT ERYTHROPOYESIS, PROBABLY ACTIVATING THE EXPRESSION OF THE ERYTHROPOIETIN RECEPTOR. In fact, erythropenia is a call for the SYSTEMIC SYSTEMAL SILENCE OF WT1 IN THE ADULT RATON._x000D_ 4) WT1's IMPLICATION IN HOMEOSTASIS OF HEART ADULT, AND THE CONSEQUENCES OF YOUR SILENCIAMIENT IN ANIMAL MODEL TO THE HUMAN. TO DATE, THE CONSEQUENCES OF CARDIO-SPECIFIC SILENCING OF WT1 IN ADULT ORGANISMS HAVE NOT BEEN STUDIED, ALTHOUGH IT IS KNOWN THAT SYSTEMIC SILENCING IN THE ADULT RATON CAUSES RAPID LOSS OF HEART MASS. _x000D_ we believe that in order to reach these OBJECTIVES we have a good working team with RESIDENT RESIDENT RESIDENT RESIDENT IN VARIOS PAYERS, whom we have already been working with and who are accountable to us. We also count on the totality of TRANSGENIC RATON models available for statistics related to WT1._x000D_ in summary, we believe that a project is being dealt with with a high capacity of knowledge management and results that can be published at a high level, that will be carried out by a working team that brings a tremendous experience, and as a result of the results, they can have real applications in the camp of the CLINICA. (English)
12 October 2021
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Málaga
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Identifiers
BFU2014-52299-P
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