Felix Laboratory Research Overview

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.

Other studies in the lab are focused on finding treatments to improve the poor outcomes in leukemias with MLL translocations. Dr. Felix leads ongoing research in this area involving 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 work with mll mutant zebrafish models 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.