My laboratory studies the epigenetic mechanisms that contribute to gene expression. A human cell contains about two meters of DNA in its tiny nucleus, presenting a phenomenal packaging problem. To manage, the cell relies on chromatin to organize its genome. Chromatin's operational structure is the nucleosome, consisting of 146 bp of DNA wrapped around a bundle of eight core histone proteins (H3, H4, H2A and H2B). The packing of nucleosomes into increasingly complex structures explains how the DNA fits. But when genes are expressed, the chromatin template must alter its structure, unpacking itself to make those genes accessible to the scores of proteins involved in transcription. Epigenetics, then, is the study of how modifications to the chromatin template establish and propagate differences in gene expression. We aim to define the epigenetic controls that contribute to tumorigenesis and cancer stem cell plasticity in Neuroblastoma, as well as the histone modifications that regulate inducible gene expression downstream of the STAT signaling pathway.

Zhong, M.; Henriksen, M.A. ; Takeuchi, K.*; Schaefer, O.; Liu, B.; ten Hoeve, J.; Ren, Z.; Mao, X.; Chen, X.; Shuai, K.; Darnell, J.E., Jr. (2005). Implications of an anti-parallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle.  Proceedings of the National Academy of Sciences USA 102, 3966-3971.  

Lerner, L.; Henriksen, M.A. ; Zhang, X.; Darnell, J.E., Jr. (2003).  Stat3-dependent enhanceosome assembly and disassembly: Synergy with GR for full transcriptional increase of the a2-Macroglobulin gene. Genes & Development 17, 2564-2577.

Henriksen, M.A. ; Betz, A.; Fuccillo, M.V.; Darnell, J.E., Jr. (2002).  Negative Regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site.  Genes & Development 16, 2379-2389.