Multimeric Pbx complexes in development and disease

We have discovered that Pbx proteins also form stable heterodimeric complexes with Meis proteins, homeodomain proteins structurally related to Pbx1.  Pbx can simultaneously interact with Hox and Meis partners, and we have observed functional trimeric interactions by these proteins on native Hox enhancers.  Our biochemical and biological evidence suggests that altered subunit composition may allow specific trimeric complexes to function as transcriptional mediators of leukemogenesis.  Furthermore, oncogenic E2a-Pbx1 fusion proteins have lost the ability to dimerize with Meis.  Current interests focus on the transcriptional effector properties of Hox-Pbx-Meis complexes, their perturbations by Hox or Pbx mutations, and the identities of target genes whose misregulation contributes to leukemias.

[Link to some of our publications on these topics]