Kathrin Bernt Laboratory
The primary interest of the Bernt Laboratory lies in investigating the role of epigenetic gene regulation in normal hematopoietic stem cells, and extending these relevant findings to the study of leukemia. Epigenetic changes in cancer are of particular interest since, in contrast to DNA sequence alterations, they are potentially reversible.
As one of the first examples of targeted modulation of a leukemogenic program through inhibition or genetic inactivation of an epigenetic modifier, Dr. Bernt was able to demonstrate that methylation of histone 3 at lysine 79 specifically controls a leukemogenic gene expression program in MLL-AF9 fusion driven leukemia cells (Bernt... Armstrong, Cancer Cell 2011). This established the H3K79 methyltransferase Dot1l as a therapeutic target for the subgroup of leukemias that carry a rearrangement of the Mixed Lineage Leukemia gene, MLL.
There is a growing appreciation that epigenetic changes play a role in a wide variety of cancers and may govern biological processes associated with relapse and refractory disease. We use a combination of genetic conditional loss of function models for transcription factors and epigenetic modifiers, murine leukemia models, primary patient material, genome wide expression and epigenetic profiling, genome editing and small molecule inhibitors to dissect mechanisms controlling stemness and self-renewal in hematopoietic malignancies. Our goal is to develop the depth of mechanistic understanding that will allow targeted pharmacologic modulation of epigenetic states as a means to develop more better therapies for our patients.
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