Research Summary

My laboratory is assembling and analyzing gene regulatory networks that orchestrate the development of various cell types of the innate and adaptive immune system including B-and T lymphocytes, macrophages, neutrophils dendritic and mast cells. These networks comprise of inter-connected transcription factors, signaling molecules and miRNAs that regulate cell fate choice and developmental transitions. We are also interested in manipulating these regulatory networks to engineer stem cells to efficiently adopt particular immune cell fates. Currently, the laboratory has the following three research foci:

I. Gene regulatory networks that dictate cell fate choices in the immune system (read more...)

II. Regulation of discrete developmental transitions within the B-cell developmental pathway (read more...)

III. Nuclear compartmentalization, transcription and recombination dynamics of immunoglobulin loci (read more...)

Figure Legend:
A proposed self-sustaining regulatory network established in a B cell precursor. It is suggested that the establishment of this network depends on transient signaling and inputs from the cytokine receptor Flk2 and the transcription factors PU.1 and Ikaros, respectively. Positive feedback loops involving the cytokine receptor IL-7R and the transcription factors EBF, E2A and Pax-5 may generate a self-sustaining circuit. The network architecture also features cross-antagonism with alternate cell fate-determining transcription factors such as GATA-1, C/EBPalpha and Notch-1. Stimulatory and inhibitory inputs are indicated as solid or dashed lines, depending on the strength of the experimental evidence.

Recent Publications

Gantner, B and Singh, H. (2007) Immunology. Short-term memory. Nature 447:916-917. (PubMed)

Littman, DR and Singh H. (2007) Immunology. Asymmetry and immune memory. Science 315(5819):1673-4. (PubMed)

Singh, H. (2007) Shaping a helper T cell identity. Nature Immunology 8(2):119-20. (PubMed)

Pongubala, J.M., Northrup, D.L., Lancki, D.W., Medina, K.L., Treiber, T., Bertolino, E., Thomas, M., Allman, D. and Singh, H. (2008) Transcription Factor EBF Restricts Alternate Lineage Options and Promotes B Cell Fate Commitment Independently of Pax5. Nat Immunol 9:203-215. (PubMed)

Johnson, K., Hashimshony, T., Sawai, C.M., Pongubala J.M., Skok, J.A., Aifantis, I. and Singh, H. (2008) Regulation of Immunoglobulin Light-Chain Recombination by the Transcription Factor IRF-4 and the Attenuation of Interleukin-7 Signaling. Immunity 28:335-345. (PubMed)

Reddy, K., Zullo, J., Bertolino, E., Singh, H. (2008) Transcriptional Repression Mediated by Repositioning of Genes to the Nuclear Lamina. Nature 452:243-247. (PubMed)

(>> Complete Bibliography)

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