Pfeifer Laboratory

Epigenetic Pathways in Disease

The Pfeifer Lab studies how epigenetic processes contribute to the etiology of cancer and potentially to other human diseases. One major research direction is aimed at understanding the mechanisms of DNA methylation and demethylation, two antagonistic processes that are disrupted in disease leading to aberrant cell function and malignant transformation. One major DNA demethylation pathway involves enzymatic oxidation of 5-methylcytosine (5mC) by TET dioxygenases leading to the formation of 5-hydroxymethylcytosine (5hmC) and additional oxidation products that are removed by DNA repair. The lab investigates how the function of TET proteins is controlled. The DNA base 5hmC is particularly abundant in neuronal cells. Ongoing studies have shown that the oxidation of 5mC is critical for the differentiation and migration of cortical neurons and that this process may help maintain long-term functionality of these postmitotic cells in the mammalian brain.