James R. Downing Lab

Our laboratory focuses on exploring the underlying molecular mechanism of one of the more common variants of human myeloid leukemias, core-binding factor acute myeloid leukemia (CBF-AML) with t(8;21) translocation. Core-binding factor acute myeloid leukemias arise via chromosomal rearrangements impairing activity of genes encoding for proteins essential for normal blood cell development. Patients with core-binding factor leukemia have a massive accumulation of abnormal cells known as myeloid blasts, including a shortage of mature blood cells.  

Chromosomal rearrangements alone are not sufficient for the development of blood cancers and this, has prompted our interest and search for additional mutations that cooperate with genetic rearrangements to cause leukemia. Scientists in our laboratory use a multidisciplinary approach that incorporates a variety of molecular tools, cell imaging, single-cell genomics and in vivo model systems to study the functional consequences of mutations in hematopoietic cells responsible in leukemic transformation.  

Our discoveries help create a better understanding of the molecular etiology of acute leukemias and lead to improvements in the ability to diagnose, risk stratify, monitor, and treat these types of catastrophic diseases in children.