Urban Gullberg

Professor

Research areas and keywords

UKÄ subject classification

  • Cancer and Oncology

Research

 

Genome-wide binding and function of isoforms and mutant forms of the Wilms' tumor gene 1 (WT1) protein in leukemic cells.

Acute leukemia is the most common cancer among children but appears also in adults at all ages. Perturbed function of several transcription factors has been implicated in the pathogenesis of leukemia, and among these is the Wilms´ tumor gene 1 protein (WT1). WT1 is commonly overexpressed in leukemia and is also recurrently mutated. In agreement with this, clinical as well as experimental data indicate WT1 as an oncogene. The full transcriptional target repertoire and function of WT1 in leukemia is, however, poorly understood. We hypothesize that certain isoforms and mutant forms of WT1 have specific DNA-binding properties. Thus, the decomposition of the normal isoform-balance, or the mutations recurrently observed in leukemia, would disorient normal transcriptional effects of WT1, contributing to the leukemic phenotype. To seek support for this hypothesis, we investigate the molecular function of different forms of WT1 genome-wide, as well as on specific target genes. We use cellular models allowing isoform- and mutantspecific chromatin immunoprecipitation, followed by deep sequencing (Chip-Seq). For gene-specific analyses, we utilize molecular biology techniques such as promoter reporter and EMSA experiments. Transcriptional effects are investigated by transduction and transcriptional profiling. The results of the investigation will provide novel insights into the pathophysiology of WT1, which could lead to development of improved therapy.

Highlighted research outputs

Carl Sandén & Urban Gullberg, 2015, In : Leukemia. 29, 8, p. 1632-1636

Research output: Contribution to journalReview article

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