Funded Investigators

Margaret Goodell, Ph.D.
Baylor College of Medicine

Investigating the Role of Dnmt3a in Development of Myeloid Malignancies

Acute myeloid leukemia, also known as AML, is the most common acute leukemia found in adults. AML is characterized by a rapid growth of abnormal white blood cells in the bone marrow and it can quickly spread to the blood and other parts of the body. Currently, the efficacy of available treatments depends on the patient’s subtype. Certain prognostic factors can improve patient outlook, but patients that lack a certain protein, DNA methyltransferase 3A and 3B (DNMT3A and DNMT3B), generally have a poor prognosis. DNMT3 is a protein that introduces methylation flags, which are a type of marker, to genes. The exact pattern of methylation flags can turn certain genes on and off, ultimately controlling a cell’s protein production. Cancer cells often exhibit an altered pattern of these markers, indicating that dysfunction of DNMT3 plays a particularly important role in the development and severity of AML.

Dr. Goodell is currently researching the role these proteins play in blood forming stem cells. Her research uses mouse models to examine how the absence of this protein affects the frequency and malignancy of tumor development. Moreover, Dr. Goodell is researching the pattern of methylation tag placement and its effect on tumor malignancy. A complete understanding of how DNMT3 mutations promote cancer can lead to the development of therapeutic interventions that are able to destroy or reprogram malignant cells.

New discoveries about stem cells and gene regulation from this research will also contribute to collaborations within the Foundation’s Institute without Walls.