AML1-ETO

We have been studying the AML1-ETO fusion protein, which is found predominantly in the FAB-M2 subtype of acute myelogenous leukemia (AML) and is generated by the t(8;21) since 1993. By understanding how it transforms hematopoietic stem cells (HSC) we hope to develop novel therapies for AML (and MDS).

MEF/ELF4

Our earlier studies of the transcriptional regulation of cytokine gene expression, led us to isolate and characterize the transcription factor MEF (aka ELF4), which we have shown regulates HSC quiescence and self-renewal. We are now defining how these processes are controlled.

Arginine Methyltransferases (PRMTs)

We are interested in understanding how the post-translational modifications that are commonly seen on histones affect the function of DNA sequence-specific binding proteins, such as AML1. We wish to target those enzymes that are involved in the malignant transformation of hematopoietic cells.

L3MBTL1

Having isolated the human homologue of the Drosophila l(3)mbt gene by exon trapping, based on its location on the long arm of chromosome 20 (20q) within a region frequently deleted in hematologic malignancies (most commonly polycythemia vera, MDS, and AML). We are investigating its role as a tumor suppressor gene and in regulating erythroid differentiation.

Epigenetic-Based Therapies (Hypomethylating Agents, Histone Modifying Enzyme Inhibitors, and Salicylates)

As part of our translational research efforts, we are examining the activity of inhibitors of gene repression and gene activiation. Mouse models have been established to look at agents such as salicylates, which modulate the activity of mitogen-activated protein kinase (MAPK) family members and inhibit nuclear factor-kappa B (NF-_B) activation.