On Thursday April 9th, 2009 Panthea Taghavi will defend her thesis titled “From LPA signaling to Polycomb; oncogenic cooperations revealed by genetic screens and dynamics and recruitment of polycomb group proteins” in order to obtain the doctorate degree from the University of Amsterdam. Her promoter is professor Maarten van Lohuizen.
To specifically eradicate tumor cells during therapeutic intervention, it is important to find cooperating oncogenic lesions and to identify the mechanism by which they direct oncogenic transformation. Research described in this thesis focuses partly on the search for novel oncogenes that cooperate with c-Myc or Ras in tumorigenesis, and partly on the mechanism of action of one of the oncogenic collaborators of c-Myc, Bmi1.
Although, c-Myc and Ras are affected in many human cancers, aberrant activation of each of them alone is not sufficient to induce transformation. These oncogenes always act in combination with other activated oncogenes or inactivated tumor suppressors. First part of the thesis describes different genetic gain-of-function screens set up to find oncogenes that can cooperate with c-Myc or RasV12 under conditions in which p19Arf tumor suppressor levels are compromised. One of the oncogenic pathways found to cooperate with c-Myc in transformation is the LPA (lipid growth factor) receptor signaling.
The second part of the thesis focuses on studying the stability and dynamic properties of Bmi1 association on chromatin during G1 and G2 of the cell cycle. Moreover, factor involved in Bmi1 recruitment to heterochromatic loci are investigated. Bmi1 is one of the most extensively studied members of the PcG proteins and was originally identified to collaborate with c-Myc in tumorigenesis through transcriptional repression of the Ink4a-Arf tumor suppressors. This study shows that PcG proteins are flexible and dynamic and introduces a novel recruitment mechanism for Bmi1.
The thesis defence is open to the public and will take place in the Agnietenkapel, Amsterdam, at 10.00 hours.