Research at the Heikamp Lab

We study a rare but aggressive form of leukemia driven by chromosomal rearrangements of the Nucleoporin 98 (NUP98) gene, which encodes a component of the macromolecular nuclear pore complex. NUP98-rearrangements (NUP98-r) produce oncogenic NUP98-fusion proteins (NUP98-fp) that bind to chromatin with other chromatin regulatory complexes, such as KMT2A (lysine methyltransferase 2A) and its binding partner Menin to promote oncogene expression characterized by high expression of the HOX genes and their cofactor MEIS1. Our goal is to understand how NUP98-fp cooperate with other epigenetic regulators to maintain an active chromatin landscape that promotes leukemogenesis. We have discovered targeting cooperating chromatin complexes (such as Menin-KMT2A) with small molecules enables us to indirectly disrupt NUP98-fp activity.

We aim to discover novel molecular dependencies in NUP98-r leukemia that can be targeted with small molecules to halt leukemogenesis. We believe that only through deep mechanistic understanding of NUP98-fp biology will we be able to translate these discoveries into new treatments for patients with NUP98-r leukemia.