Dr. Ellen Rothenberg's group works at the interface of developmental biology, immunology, genomics, and systems biology, focusing on gene networks that control early T-cell development. Their goal is to generate a comprehensive explanation at the molecular level for the process of T-lymphocyte development from mouse hematopoietic stem/progenitor cells. Of greatest interest are the lineage choice events through which cells select the T-cell fate and exclude other developmental pathways. Rothenberg’s group has optimized in vitro differentiation technology to determine the sequence of changes in the cells and generated detailed gene expression profiles for transitions from stage to stage. This system also makes possible detailed gain and loss of function experiments to test the roles of important transcription factors which turn out to have sharply delineated effects on stage to stage progression. Recently, her group's analysis of the T-cell specification process has been extended to a genome-wide scale. This work is now providing a comprehensive picture of the stepwise transcriptional and epigenetic changes brought about by altered transcription factor activity, and thus how transcription factors sequentially control acquisition of T-cell identity.
Selected Cancer-Related Publications:
Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV. Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell. 2012 Apr 13;149(2):467-82.
Rothenberg EV. Transcriptional drivers of the T-cell lineage program. Curr Opin Immunol. 2012 Apr;24(2):132-8. Epub 2012 Jan 19
Li L, Leid M, Rothenberg EV. An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science. 2010 Jul 2;329(5987):89-93.
Rothenberg EV, Zhang J, Li L. Multilayered specification of the T-cell lineage fate. Immunol Rev. 2010 Nov;238(1):150-68.
Georgescu C, Longabaugh WJ, Scripture-Adams DD, David-Fung ES, Yui MA, Zarnegar MA, Bolouri H, Rothenberg EV. A gene regulatory network armature for T lymphocyte specification. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20100-5. Epub 2008 Dec 22