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Dr. Grant Challen
Aberrant epigenetic marks such as DNA methylation and histone modification patterns are widely reported in human hematopoietic malignancies, but the pathological consequences of these marks remain to be defined. Moreover, genetic mutations in a number of critical components of the epigenetic machinery have recently been discovered in wide range of hematopoietic diseases such as acute myeloid leukemia, myelodysplastic syndromes, and T-cell leukemia / lymphoma. There is mounting evidence for the importance of epigenetic mechanisms in the regulation of stem cell function, and this area of study represents one of the next major fields of stem cell biology. As a post-doctoral fellow at Baylor College of Medicine, Dr. Grant Challen identified a crucial role for the DNA methytransferase enzyme Dnmt3a in hematopoietic stem cell self-renewal versus differentiation fate decisions. In his independent research laboratory at Washington University in St. Louis, Dr. Challen has extended these studies into mouse models of hematopoietic transformation and show that loss of Dnmt3a in the bone marrow leads to the development of myelodysplastic syndromes after long latency. His lab is using global next-generation sequencing methods to identify the epigenetic marks associated with developmental fate decisions during hematopoiesis, and using genetic mouse tools to dissect the roles of the epigenetic modifiers in malignant transformation.