UCL Cancer Institute Seminar Series

Professor Mikael Sigvardsson, Lund University, presents: Shaping up a cellular lineage: Lessons from normal and malignant B-lymphocyte development, Thursday 3 October 12pm

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

Professor Mikael Sigvardsson academic profile

Hosted by: Professor Tariq Enver

The seminar will be followed by a sandwich buffet lunch

Selected publication:

Jensen CT, Strid T, Sigvardsson M. Exploring the multifaceted nature of the common lymphoid progenitor compartment. Curr Opin Immunol. 2016 Apr;39:121-6. doi: 10.1016/j.coi.2016.01.009. Epub 2016 Feb 9.

Mahadesh A. J. Prasad, Jonas Ungerbäck, Josefine Åhsberg, Rajesh Somasundaram, Tobias Strid, Malin Larsson, Robert Månsson, Ayla De Paepe, Henrik Lilljebjörn, Thoas Fioretos, James Hagman and Mikael Sigvardsson. Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency. Blood 2015 125:4052-4059; doi:10.1182/blood-2014-12-617282

Location

Courtyard Café
UCL Cancer Institute
Paul O'Gorman Building
London, WC1E 6DD

Contact: Veronica Dominguez v.dominguez@ucl.ac.uk

This seminar has been part-sponsored by Merck, the Biomedical Research Centre and Cancer Research UK