Epigenetic alterations, including DNA methylation, histone covalent modifications and super-enhancer regulation of exceptional transcriptional states, have attracted a significant amount of attention for the prevention and treatment of different genetic disorders with cancer at the forefront, mainly due to the inherent reversibility of epigenetic states. Acute myeloid leukemia (AML) is the third most prevalent cancer among the hematological malignancies in the United States, presenting with a diverse array of epigenetic abnormalities including chromosomal alterations or recurrent mutations in the epigenetic modifiers.
Dr. Choudhury’s laboratory investigates the epigenetic regulatory mechanisms at the enhancers and promoters of the critical oncogenes and tumor suppressors that drive malignant proliferation and invasion during leukemogenesis across the molecular subgroups of AML patients. Using the multi-omics platform, we intend to identify the alterations in DNA-methylation, histone covalent modifications, and accessibility of the transcription factors to the aberrantly expressed genes in and outside the topologically assorted domains of the leukemic blasts. We employ a combination of in vitro and in vivo mouse models to design and target CRISPR or small molecule based perturbation strategies to reverse the dysfunctional epigenetic states and malignant growth.