Daniel Steven Gary Wechsler
Associate Professor of Pediatrics

Our laboratory is primarily focused on understanding the pathogenesis of childhood leukemias. This interest developed after treating an infant with acute myeloid leukemia (AML), whose leukemia cells carried a novel chromosomal translocation, MLL-CALM . The CALM gene, which encodes for a protein involved in endocytosis, is also found in CALM-AF10 translocations, which are seen in 5-10% of T cell leukemias. In studies to identify which particular domains of CALM contribute to leukemogenesis, we determined that CALM contains a nuclear export signal (NES) that is necessary and sufficient for imparting leukemogenic properties to CALM-AF10. The NES interacts with CRM1/XPO1, a nuclear chaperone protein that is involved in exporting proteins from the nucleus to the cytoplasm. We have recently found that CRM1 contributes to the upregulation of HOXA genes, which are essential mediators of leukemogenesis. We are currently exploring the mechanisms by which CRM1 modulates HOXA  gene expression, focusing on mutational analysis of critical CRM1 domains and the identification of CRM1-interacting partner proteins. Given the ability of CRM1 to regulate transcription of HOXA genes, we are also seeking to identify additional non-HOXA CRM1 target genes. Finally, we also take advantage of compounds that inhibit CRM1 function (SINEs - Selective Inhibitors of Nuclear Export) that are being used in both preclinical and early phase clinical trials, to dissect out CRM1-dependent functions.

     The lab uses molecular, cellular and in vivo mouse studies taking advantage of well-established murine leukemia models. By developing a better understanding of CALM and CRM1 function in normal and malignant hematopoiesis, we will be able to develop new therapeutic approaches for difficult-to-treat infant and pediatric leukemias.

Current Appointments and Affiliations

Contact Information

  • 397 Hanes House, Durham, NC 27710
  • DUMC Box 102382, Durham, NC 27710

Some information on this profile has been compiled automatically from Duke databases and external sources. (Our About page explains how this works.) If you see a problem with the information, please write to Scholars@Duke and let us know. We will reply promptly.