Group Leader

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Prof. Dr. Rudolf Grosschedl
Senior Group Leader & Director
Phone:+49 761 5108 711

Lab Rudolf Grosschedl

Assistant: Marika Rott Phone: +49 761 5108 711 Email: rott@ie-freiburg.mpg.de

Selected Publications

1.
Boller S, Ramamoorthy S, Akbas D, Nechanitzky R, Burger L, Murr R, Schübeler D, Grosschedl R (2016)
Pioneering Activity of the C-Terminal Domain of EBF1 Shapes the Chromatin Landscape for B Cell Programming
2.
Rosenbaum M, Andreani V, Kapoor T, Herp S, Flach H, Duchniewicz M and Grosschedl R (2014)
MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress
3.
Nechanitzky R, Akbas D, Scherer S, Györy I, Hoyler T, Ramamoorthy S, Diefenbach A, and Grosschedl R (2013)
Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells
4.
Györy I, Boller S, Nechanitzky R, Mandel EM, Pott S, Liu ET, Grosschedl R (2012)
Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells
5.
Kieslinger M, Hiechinger S, Dobreva G, Consalez GG, Grosschedl R. (2010)
Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner

Laboratory Rudolf Grosschedl

Laboratory Rudolf Grosschedl

The developmental potential and trajectory of a cell are influenced by external signals and internal conditions, including the epigenetic state and the activity of transcription factors. Hematopoiesis is one of the best characterized developmental systems for studying cell fate decisions, differentiation, lineage-specific gene expression and plasticity of transcriptional and chromatin states.

In particular, B lymphopoiesis is an excellent paradigm for the stepwise differentiation of multipotent progenitors into terminally differentiated effector cells. Differentiation of multipotent progenitors into effector lineages requires multiple changes in transcriptional and chromatin states.

These include:

  1. multilineage priming of enhancers implicated in setting a chromatin state permissive for gene activation,
  2. expression of lineage-specific transcription factors that establish de novo accessibility of cis-regulatory elements,
  3. combinatorial action of transcription factors that form complex regulatory networks and activate lineage-specific gene programs and
  4. repression of transcriptional programs associated with alternative cell fates to stabilizes lineage decisions and commit cells to a specific cell fate.

We address questions of how lineage-specific transcription factors establish accessibility in naïve chromatin of hematopoietic progenitors, how specific combinations of transcription factors activate a lineage-specific program of gene expression and how transcription factors and cis-acting sequences form regulatory networks that establish and maintain B cell identity.

Other questions include the role of higher-order chromatin structure and the function of transcription factors in the regulation of stem cell pluripotency. Finally, we seek to understand which signals from stromal cells influence transcriptional determinants of B lymphopoiesis and which genes regulate functional differences between conventional and innate-like B cells.

 
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