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LEUKEMOGENESISAPL

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An in vivo Screen for the Identification of Leukemia Promoting Factors

The proposed research aims to identify and characterize factors conferring leukemic properties to hematopoietic cells. This screen will be based upon a murine leukemia model I have developed in my time at the Salk Institute (La Jo... ver más

31/08/2014

UKE

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

UNIVERSITAETSKLINIKUM HAMBURGEPPENDORF No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2014-08-31 No tenemos la información de la convocatoria

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Líder del proyecto

UNIVERSITAETSKLINIKUM HAMBURGEPPENDORF No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The proposed research aims to identify and characterize factors conferring leukemic properties to hematopoietic cells. This screen will be based upon a murine leukemia model I have developed in my time at the Salk Institute (La Jolla, CA) these mice express a fusion of RARalpha with three FKBP12 Rapamycin-regulated dimerization domains FKBP12 F36M (F3-RARa). These F3-RARa TG mice, though healthy, exhibit a preleukemic state that is more accessible to transformation by cellular factors, such as activated cytokine receptors. (Sternsdorf et al, 2006). At low frequency, these mice spontaneously develop myeloid leukemia with APL features. From these leukemias I want to identify leukemogenic factors. Freshly expanded Leukemia cells will be used to generate a retroviral cDNA library. Initially, I will use this library to transduce non-transplantable murine cell lines and test, which factors convey transplantability. In the following, I will transduce /transplant pre-leukemic bone marrow from younger F3-RARa mice. This should lead to leukemias, which will be tested, isolated by cell sorting, according to presence of viral integrate (GFP). Leukemias will be FACS-isolated by phenotype (GFP, Surface markers). The integrated retroviral vectors will be isolated by PCR. The goal of this analysis is to identify and characterize novel cellular factors, involved in the process of leukemia development. This will enable me to identify novel potential targets for therapy. I am an experienced scientist in the earlier part of my career: after spending nine years in the US, I am returning to the European Union. A Heisenberg Fellowship (Germany) made this possible. This fellowship, though prestigious, covers only a small amount of funding besides my salary. Therefore I consider the IRG a critical component of funding in this critical time of my career and the successful transfer of my knowledge to the hosting lab in Hamburg.

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