The complex interplay between the genetic mutations, epigenetic abnormalities, chromatin transitions and the resultant transcriptional states driving the tumorigenesis process remains an enigma still and has been the focus of my research for the past 15 years. Currently, I am examining the chromatin and epigenetic mechanisms underlying the hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Recurrent mutations in the de novo DNA Methyltransferase, DNMT3A are one of the earliest events representing a premalignant phase of AML termed as clonal hematopoiesis of indeterminate potential (CHIP). Preleukemic DNMT3A mutations have an origin in the multipotent hematopoietic stem cells (HSCs) that causes a differentiation blockade and a disproportional outgrowth of HSC clones. We are therefore interested in gaining a deeper understanding of the role of DNMT3A mutations during CHIP and leukemic development, taking advantage of a novel Confetti lineage tracing mouse model for tracking the clonal dynamics and progression, along with a variety of functional and multi-omics approaches. Through these studies, we hope to uncover the molecular mechanisms that predispose the patients to leukemia which should pave way for new targeted preventative treatment strategies.