Emeritus Laboratory Rudolf Grosschedl

Emeritus Laboratory Rudolf Grosschedl

Cellular and Molecular Immunology

Differentiation of hematopoietic stem cells to specialized effector cells involves multiple cell fate choices and a progressive loss of lineage potential.  We study how transcription factors change the epigenetic landscape, activate cell type-specific gene expression and ensure the maintenance of lineage identity.  We use B lymphopoiesis as a model system and investigate how progenitor cells commit to the B cell lineage.  We found that EBF1 acts as a pioneer transcription factor that regulates the transition of naive progenitor chromatin to B-lineage-committed chromatin.  In addition, we examine the role of Satb transcription factors in the regulation of higher-order chromatin and differentiation of B cells and embryonic stem cells.

Approach

We use gene editing, genome-wide molecular and cell biological approaches in combination with primary cell transduction and mouse transgenic analysis to gain insight into the regulatory networks of B cell differentiation.

Impact

Our research is aimed at understanding how the correct dosage and function of transcription factors safeguard B lymphoid cells against leukemic transformation.


Selected Publications

1.
Wang Y, Zolotarev N, Yang CY, Rambold A., Mittler G, Grosschedl R (2020)
A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin
Immunity 53(6), 1151-1167.e6
2.
Derecka M, Herman JS, Cauchy P, Ramamoorthy S, Lupar E, Grün D, Grosschedl R (2020)
EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential
Nature Immunology 21, 261-273.
3.
Li R, Cauchy P, Ramamoorthy S, Boller S, Chavez L, Grosschedl R (2018)
Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming.
Genes Development 32, 96-111.
4.
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
Genes & Development 28(11), 1165-1178, 1 June 2014.
5.
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
Nature Immunology 14(8), 867-875.

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