March 1 2016
[Date and Time]
March 10, 2016. Thursday 17:00-18:00
1F Conference Room, Institute of Molecular Embryology and Genetics (IMEG)
Professor Mikael Sigvardsson, Ph.D.
Medical Molecular Biology, Linkoping University, Sweden
Molecular Hematology, Lund University, Sweden
The development of mature blood cells from multipotent stem cell is a complex process involving the coordinated activity of transcription factor networks and extracellular signals. We have explored the molecular regulation of B-lymphocyte development using transgenic mouse models. This has revealed that the process involve distinct phases, specification resulting in the activation of the B-lineage program and commitment to abolish alternative cell fates. Even though these processes are linked via auto-regulatory loops they can be functionally separated. The differentiation pathway is linked to malignant transformation thought the action of the transcription factors EBF1 and PAX5, acting in a dose dependent manner to prevent malignant transformation. The seminar will focus on our recent findings revealing that disruption of transcription factor networks in B-cell leukemia allow for plasticity mediating a cross linage transfer of the leukemic state to generate T-lineage disease. Further, the seminar presents a protein association analysis revealing novel regulatory networks involving the targeting of broadly expressed DNA binding proteins to lineage restricted target genes by lineage specifying transcription factors.