David P. LeBrun, MD

Email: lebrun (at) path.queensu.ca
Office Phone: 613-533-3209
Fax: 613-533-6830

Our lab carries out experimental and correlative research related to hematological cancers. The experimental component of our work is directed at understanding the molecular mechanisms that underlie acute lymphoblastic leukemia, an aggressive and relatively common cancer in children. We are especially interested in an oncogenic transcription factor called E2A-PBX1.

The figure illustrates how an amino-terminal portion of the E2A gene product E47, a DNA-binding transcription factor that regulates target genes involved in B-lymphoid development, becomes fused to a portion of PBX1, a homeodomain-containing transcription factor, to create oncogenic E2A-PBX1. E2A-PBX1 disrupts the normal regulation of cellular proliferation and differentiation by mechanisms that involve physical interactions with other proteins and DNA; these ultimately lead to abnormal gene regulation. Essentially, we use a wide range of techniques, including a variety of biochemical and cell biology experiments and mouse models, to identify and elucidate key physical and functional molecular interactions involved in transforming normal hematopoietic cells into leukemic ones. Since some of these interactions represent potential drug targets, we are carrying out screens to identify small molecules that disrupt them and thereby provide clues for the development of potential new leukemia drugs.

Exciting new experimental avenues include biophysical and structural experiments being carried out in collaboration with Dr. Steven Smith, in the Queen's Department of Biochemistry, and the characterization of signaling pathways that collaborate with E2A-PBX1 to transform primary B-lineage lymphoid cells.