Emily B. Heikamp, MD, PhD

Dana-Farber Cancer Institute

Academic Titles

Assistant Professor, Pediatrics, Harvard Medical School

Research Program Affiliation

Member, Leukemia

Member, Cancer Genetics and Epigenetics

Research Abstract

My laboratory studies acute myeloid leukemia (AML) driven by chromosomal translocations that produce oncogenic fusion proteins, which are potent drivers of leukemogenesis. We aim to understand how these fusion proteins promote epigenetic dysregulation by hijacking chromatin regulatory complexes, and how these pathways can be exploited therapeutically to induce differentiation and halt self-renewal in AML.

Our work focuses on a subset of fusion protein-driven leukemias that share a stem cell-associated gene expression program characterized by high expression of homeobox (HOX) genes and their cofactor MEIS1. We have discovered that small molecules disrupting chromatin regulatory complexes that cooperate with oncogenic fusion proteins can indirectly inhibit fusion protein activity, resulting in downregulation of the HOX/MEIS program and leukemia cell differentiation.

Beyond these translational applications, we seek to understand the fundamental mechanisms by which diverse oncogenic fusion proteins converge on this shared HOX/MEIS program. While many genes involved in chromosomal translocations in HOX/MEIS leukemias have well-defined roles in hematopoiesis and leukemogenesis, others remain completely unexplored. Using an integrated approach that combines functional genomics, chromatin biology, biochemistry, pharmacology, and live cell imaging, our goal is to systematically define the roles of translocation-associated genes in both normal and malignant hematopoiesis.

This comprehensive strategy enables us to identify and validate novel therapeutic targets, develop selective small molecule inhibitors, and advance precision medicine approaches for patients with high-risk AML.