Our laboratory has two major research interests:
1)We are currently investigating the role of MLL-CALM, a novel hybrid protein first identified in the leukemic blasts of an infant with acute myeloid leukemia (AML), in myeloid leukemogenesis. Expression of MLL-CALM disrupts endocytosis and intracellular vesicle transport, processes involved in regulation of growth factor signaling. The lab is actively involved in understanding which domains of CALM contribute to perturbation of endocytosis, and whether restored endocytosis results in decreased leukemogenesis. These studies are carried out both in vitro
and in vivo
, taking advantage of CALM-deficient fit1
mice. We have also recently determined that CALM plays a previously unrecognized role in transcriptional regulation, and we are in the process of defining the importance of the CALM transcriptional activation domain in leukemogenesis. A better understanding of CALM's function in normal and malignant hematopoiesis also has implications for the pathogenesis of other malignancies.
2)In addition, our lab is continuing to address the function of Mxi1, a Myc antagonist, in the pathogenesis of neuroblastoma, the most common extracranial solid tumor of childhood. We have recently been focused on a novel role for Mxi0, an alternatively transcribed Mxi1 isoform that appears to lack the transcriptional repression properties of Mxi1. Expression of MXI0 appears to correlate with that of MYCN, suggesting coordinate regulation. The identification of MXI0 deepens the complexity of regulation by MYC family members in neuroblastoma, and raises the possibility of novel therapeutic interventions for these difficult to treat tumors.