Wagenblast, Elvin PHD

PROJECT NARRATIVE DNA a to on hematopoietic therapeutic quality methylation is a crucial epigenetic mechanism that regulates genome function and RNA expression, playing pivotal role in the establishment, development, and maintenance of human hematopoiesis. This project aims investigate the unique DNA methylation patterns in trisomy 21-associated hematopoietic stem cells, focusing their impact on early cell fate decisions, self-renewal, and lineage priming, which predispose individuals to disorders and leukemia. An improved understanding of these mechanisms may reveal novel t argets for diseases associated with dysregulated DNA methylation, significantly enhancing the of life for individuals with Down syndrome.

Children with Down syndrome have a significantly increased risk of developing preleukemia during early childhood compared to children without Down syndrome. Our proposal aims to determine the molecular mechanisms that underlie the predisposition of trisomy 21 versus disomic hematopoietic stem cells towards initiating the preleukemic condition transient abnormal myelopoiesis. We are employing a combination of multi- omic analyses of human primary trisomy 21 fetal liver samples and subsequent functional interrogation using CRISPR/Cas9-mediated genome editing to uncover fundamental mechanisms and therapeutic targets of preleukemia in Down syndrome.