Research in my laboratory is centered on the mechanism and function of autosomal monoallelic expression (MAE) – an epigenetic mechanism leading to epigenetic mosaicism in human tissues, such that some genes are expressed from one allele in a given cell, and from the other allele in neighboring cells. Our laboratory work over the past few years has revealed the unexpected prevalence and importance of monoallelic expression, offering insights into its biology, evolution, and relevance for disease. Systematic research on MAE has been especially difficult due to the lack of appropriate experimental and computational tools. In response, we have developed several novel approaches to circumvent this barrier and used them to advance the literature.
The first result of that work was our discovery that the prevalence of MAE is unexpectedly high, affecting many hundreds of human genes [Gimelbrant et al., Science, 2007]. We have also used our expertise in allele-specific analysis to address different biological questions, including the process of X chromosome inactivation in human embryonic stem cells, in collaboration with the Jaenisch lab at MIT [Lengner & Gimelbrant et al., Cell, 2010] and the genetic and epigenetic interactions in breast cancer subtypes, as a collaboration with the Polyak lab at DFCI [Su et al., Cell Report, 2015].