EPIGENETIC MEMORY AND INHERITANCE
DNA methylation and histone modifications are remodeled extensively during early mammalian development, leading to the establishment of gene expression programs that cells maintain over subsequent cell divisions and differentiation - a process called epigenetic memory.
We seek to understand the interplay between DNA methylation and histone modifications that allow for epigenetic memory and discover the factors that mediate these processes in mammalian cells.
How is epigenetic memory exquisitely established? How are the marks spread across chromatin, maintained durably through cell division, and transmitted from one generation to the next generation?
CRISPR-BASED EPIGENOME EDITING
Programmable epigenome editing technologies remodel the epigenetic landscape in mammalian cells without the need to induce DNA breaks, leading to the resetting of transcription at a desired level (repression/activation).
We seek to develop new CRISPR-based epigenome editing technologies by fusing catalytically dead Cas9 to chromatin writer/eraser/reader proteins and apply these technologies genome-wide. These tools enable fine-tuned programming of gene expression for cell and tissue engineering and in vivo therapeutic applications.
DNA METHYLATION: BIOLOGY AND DISEASE
DNA methylation is an essential epigenetic modification that can regulate gene expression, such as repressing transposable elements and establishing genomic imprinting. Mutations of DNA methyltransferases, demethylases, and DNA methylation ‘reader’ proteins are implicated in cancer and neurological diseases. By studying the fundamental functions of these proteins at the systems-wide, cell biology, and biochemical levels, we seek to understand how aberrant writing, erasing, and reading of DNA methylation marks can directly lead to disease.