Our lab is interested in understanding the epigenetic basis of gene regulation in stem cell biology, development and cancer. Our work focuses on the role of DNA methylation and demethylation in gene regulation with an emphasis on the Tet family of enzymes (Tet1/2/3). Tet enzymes promote DNA demethylation by converting the DNA base 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and other derivatives. These enzymes are abundant in various cell types including the zygote, embryonic stem cells, germ cells, hematopoietic stem cells and neurons.
The lab specializes in state-of-the-art technologies of genome engineering in mouse and human embryonic stem cells and iPSCs and generating complex strains of conditional, inducible, transgenic and knockout mice to dissect epigenetic pathways and mechanisms in vitro and in vivo. We utilize embryonic stem cells, induced pluripotent stem cells and mice as model systems to study how Tet enzymes and DNA methylation/hydroxylation reshape the epigenome and regulate development and cancer.
Current projects in our lab seek to define:
How gene expression programs in embryonic stem cells are regulated by Tet enzymes, and how these mechanisms influence the biology of stem cells (self renewal & pluripotency) and embryonic development.
How embryonic stem cell lineage specification and commitment during development are regulated by Tet-mediated DNA hydroxylation and gene regulation.
How Tet enzymes are regulated in embryonic stem cells, and how these mechanisms control the dynamics of DNA methylation/hydroxylation and gene expression in pluripotent stem cells.
How hematopoietic stem cell biology and normal hematopoiesis are regulated by Tet-mediated gene regulation and how loss of Tet proteins (as reported in several blood malignancies) promotes onset of hematologic cancers.
Our work investigates novel biological roles of DNA modifying enzymes in stem cells, development and cancer. This line of research will help us better understand the biology of stem cells at the molecular, cellular and organismal levels and could lead to identification of new markers and targets for enhancing stem cell applications in regenerative medicine or treating diseases like cancer. For further details on our research please see our publications.