Current Research and Scholarly Interests
EPIGENETIC REGULATION OF DIFFERENTIATION AND DEVELOPMENT
The biological question that is driving our research in the long-term is understanding the epigenetic basis of vertebrate development and differentiation. Although each cell of a multicellular organism is a progeny of a single zygote, and shares the same genetic information with every other cell, cells differentiate to specialized forms such as skin, muscle or nervous cells. Thus, new information emerges during development, and is inherited in a way that does not involve changes in DNA sequence. This fascinating process is called epigenesis. Epigenetic changes underlie not only normal, but also pathological development. Abnormal transmission of epigenetic information contributes to human pathology, such as aging, cancer, degenerative diseases, developmental defects and mental retardation.
In the last decade evidence emerged that a substantial portion of epigenetic information is transmitted in a form of chemical modifications of histones and associated DNA. Our research focuses on understanding the mechanistic basis by which covalent histone modifications regulate gene expression patterns during vertebrate development and differentiation. In particular, we are focusing on characterizing enzymatic activities responsible for "writing" the methyl mark on histones, called histone methyltransferases, as well as on downstream effectors, or "readers", which recognize the methyl marks and translate them into specific biological outcomes. The outstanding questions we are trying to address are: How are methylation patterns established? How do methyltransferases connect to the signaling pathways? What are their roles in regulating development and how did they functionally specialize during vertebrate evolution?
A second major area of our interest involves chromatin regulation in embryonic stem cells (ESCs), molecular basis of pluripotency and role of histone methyltransferases in cell fate decisions. ESCs share with the early embryo the potential to produce every type of cell in the human body. This rare biological property is known as pluripotency. Pluripotency is a unique epigenetic state, in that ESCs can self-renew, while retaining the potential for multilineage differentiation. We are investigating the role of writers and readers of histone methylation in human and mouse ESC self-renewal and commitment to different cell fates.