Professor of Pathology
Harvard Medical School
NRB-854B
77 Avenue Louis Pasteur
Boston, MA 02115
PH: 617-432-4318
FX: 617-432-1313
yshi@hms.harvard.edu

Research Interests

A major focus of my lab is to understand epigenetic regulation and its role in human diseases.  Specifically, we are interested in histone methylation, which has been linked to epigenetic inheritance.  Histone N-terminal tails are methylated at multiple lysine residues, and the same lysine residue can be mono-, di- and trimethylated, thus endowing histone methylation powerful regulatory potentials.  Histone methylation has been associated with both transcriptional activation and repression.  Increasing evidence suggests that histone methylation also plays an important role in human cancer and other debilitating diseases such as neurological disorders.  Given the roles histone methylation plays, it was important to understand whether histone methylation was reversible.  Histone methylation has long been thought to be static and irreversible.  However, our finding of the first histone demethylase LSD1 has disapproved this dogma.  We and others have subsequently identified a host of histone demethylases that display site- and methyl group specificities.  Collectively, these findings firmly established the notion that histone methylation is dynamically regulated by both histone methylases and demethylases.  We are currently addressing the issues of mechanisms and biology of these newly identified histone demethylases.

Another focus of my lab is on Yin Yang 1, a transcription factor that was initially isolated by us as a target of adenovirus E1A oncoproteins.  Our recent findings suggest that YY1 plays an important role in mediating communications among non-contiguous DNA elements as well as in DNA repair.  Further investigations of YY1 in these processes will provide new and important insights into these fundamental biological processes in mammals.

Publications

Liu, HF, Schmidt-Supprian, M., Shi, YJ., Hobeika, E., Barteneva, N., Reth, M., Skok, J., Rajewsky, K., and Shi, Y. (2007). Yin Yang 1 regulates the immunoglobulin heavy chain gene V to DJ recombination by controlling IgH locus contraction. Genes & Dev, In press

Iwase, S, Lan, F., Bayliss, P., de la Torre-Ubieta, L., Qi, H., Huarte, M., Whetstine, JR.,Bonni, A., Roberts, T., and Shi, Y. (2007). The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases.  Cell Vol 128:1077-88.

Whetstine, JR., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G.,Colaiacovo, M., and Shi, Y. (2006). Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell Vol 125:467-81.

Shi, YJ., Lan, F., Matson, C., Mulligan, P., Whetstine, JR., Cole, PA., Casero, RA. and Shi, Y. (2004).  Histone demethylation mediated by the nuclear amine oxidase homolog LSD1.  Cell Vol 119:941-953.