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.
Zarnegar MA, Rothenberg EV. Ikaros represses and activates PU.1 cell-type-specifically through the multifunctional Sfpi1 URE and a myeloid specific enhancer. Oncogene. 2012 Jan 9. doi: 10.1038/onc.2011.597. [Epub ahead of print]
Kueh HY, Rothenberg EV. Regulatory gene network circuits underlying T cell development from multipotent progenitors. Wiley Interdiscip Rev Syst Biol Med. 2012 Jan-Feb;4(1):79-102. doi: 10.1002/wsbm.162. Epub 2011 Oct 4.
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, Moore JE, Yui MA. Launching the T-cell-lineage developmental programme. Nat Rev Immunol. 2008 Jan;8(1):9-21.