Carolyn A. Felix Laboratory
Led by Carolyn A, Felix MD, researchers in the Felix Laboratory are studying the molecular mechanisms underlying the formation of chromosomal translocations of the Mixed-Lineage Leukemia (MLL) gene and the effects of MLL translocations on the development of high-risk forms of leukemia that occur in infants and as a chemotherapy complication. The goal of the research conducted in this laboratory is to develop preventative strategies and less toxic, targeted new treatments for infant leukemias and secondary leukemias that occur as a chemotherapy complication.
Ongoing research in the Felix Laboratory using unique molecular tools invented at the Center for Childhood Cancer Research point to a molecular mechanism by which the DNA cutting protein topoisomerase II (TOP2) is the mediator of the DNA damage to the MLL gene that leads to translocations. Because MLL translocations are prevalent in leukemia in infants as well as in leukemia that occurs as a chemotherapy complication, identification of this mechanism may aid in the discovery of interventions to thwart the development of these forms of leukemia.
Due to the poor outcome in leukemias with MLL translocations, other studies in the Felix laboratory are focused on finding better treatments. Ongoing research led by Dr. Felix in this area involves the preclinical development of the anti-viral agent ribavirin as a new treatment for infants younger than one year old who develop often fatal acute lymphoblastic leukemia (ALL) with MLL gene translocations. These studies led Felix lab investigators to uncover that expression of the protein eIF4 is frequently elevated across infant ALL. This is significant because eIF4E can be in inhibited using ribavirin, ribavirin does not have the toxicities of conventional therapies, and preclinical studies in the Felix lab indicate that ribavirin has anti-leukemia activity against this form of leukemia.
Additional studies in the Felix Laboratory are using mll mutant zebrafish and transgenic zebrafish carrying a human MLL gene translocation (developed at the Center for Childhood Cancer Research) to better understand the role of the MLL gene in normal hematopoiesis, as well as the role of MLL translocations that occur early in embryogenesis in the development of fatal infant leukemias.
Future studies in the Felix Laboratory will continue to focus on elucidation of the underlying molecular mechanisms by which MLL gene translocations occur and contribute to the pathogenesis of infant and chemotherapy-induced leukemias and identification of new targeted anticancer treatments that are more effective and less toxic than existing therapies for these forms of leukemia.