The Melnick Laboratory investigates the molecular and epigenetic mechanisms driving blood cancers, with a focus on diffuse large B-cell lymphoma, acute myeloid leukemia, and related malignancies. Our research integrates functional genomics, 3D chromatin architecture, and single-cell technologies to uncover how transcriptional and epigenetic regulators—such as BCL6, CREBBP, EP300, and EZH2—control oncogenic programs and immune evasion. We aim to translate mechanistic discoveries into precision therapies by identifying druggable vulnerabilities in the malignant epigenome and tumor microenvironment. Through interdisciplinary collaboration, we bridge basic and clinical science to improve diagnosis, treatment, and outcomes for patients with hematologic malignancies.

Our laboratory has redefined the boundaries of what is “druggable” in blood cancer, pioneering rationally designed transcription factor and signaling inhibitors now advanced by major pharmaceutical companies for Blood cancer patients. We have uncovered the molecular and epigenetic circuitry of lymphoma and leukemia, from BCL6 biology and enhancer reprogramming to the oncogenic mechanisms of IDH and EZH2 mutations—discoveries that led directly to FDA-approved and clinically tested targeted therapies. Our work has revealed how 3D genome architecture, metabolic dependencies, and tumor-immune interactions shape cancer evolution, therapy response, and relapse. By translating these insights into precision treatments—including trials tailored for high-risk and minority patients—we are transforming the landscape of blood cancer care and improving outcomes worldwide.