Ellen Rothenberg, PhD
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.
Longabaugh WJR, Zeng W, Zhang JA, Hosokawa H, Jansen CS, Li L, Romero-Wolf M, Liu P, Kueh HY, Mortazavi A, Rothenberg EV. Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network. Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):5800-5807. doi: 10.1073/pnas.1610617114.
Kueh HY, Yui MA, Ng KK, Pease SS, Zhang JA, Damle SS, Freedman G, Siu S, Bernstein ID, Elowitz MB, Rothenberg EV. Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment. Nat Immunol. 2016 Aug;17(8):956-65. doi: 10.1038/ni.3514. Epub 2016 Jul 4.
Yui MA, Rothenberg EV. Developmental gene networks: a triathlon on the course to T cell identity. Nat Rev Immunol. 2014 Aug;14(8):529-45. doi: 10.1038/nri3702. Review.
Kueh HY, Champhekar A, Nutt SL, Elowitz MB, Rothenberg EV. Positive feedback between PU.1 and the cell cycle controls myeloid differentiation. Science. 2013 Aug 9;341(6146):670-3. doi: 10.1126/science.1240831. Epub 2013 Jul 18. Erratum in: Science. 2013 Oct 18;342(6156):311. Champhekhar, Ameya [corrected to Champhekar, Ameya].
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.