We investigate the epigenetic mechanisms governing the biology stem cells, 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. Tet enzymes also partner with chromatin modifiers and transcription factors to activate or repress genes in enzymatic independent manner. Tets and 5hmC are abundant in various cell types including the zygote, embryonic stem cells (ESCs), hematopoietic stem cells (HSCs) and neural stem cells (NSCs). TET mutations or deregulation have been reported in several human neurodevelopmental and neurodegenerative diseases as well as in various cancers such as leukemias.
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 Tet catalytic and non-catalytic functions regulate gene expression programs and pluripotency of ESCs.
How Tet enzymes regulate neural lineage specification and NSC biology during development.
How Tet proteins regulate the emergence and homeostasis of HSCs.
How Tet enzymes contribute to etiology of neurodegenerative diseases and hematologic malignancies.
This line of research will help us understand the epigenetic basis of regulation of stem cells, development and diseases at the molecular, cellular and organismal levels. It could also 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 in the next tab or on PubMed .