Grant Challen, PhD
Associate Professor Department of Medicine - Oncology Division - Molecular Oncology Section
Dr. Challen’s work in understanding the molecular regulation of hematopoietic stem cells is motivated by his desire to improve the lives of patients afflicted with hematopoietic disorders. His ultimate career goal is to see the implementation of meaningful discoveries in basic biology help drive novel clinical outcomes. He believes that deciphering the contribution of epigenetic factors in hematopoiesis could ultimately lead to novel therapeutic approaches for a wide range of patients.
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 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. 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, Grant 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, Grant has extended these studies into mouse models of hematopoietic transformation and shown that loss of Dnmt3a in the bone marrow leads to the development of myelodysplastic syndromes after long latency. The observation that hypomethylating agents such as decitabine can induce a clinical response in a subset of patients highlights the importance of targeting epigenetic marks in cancer therapy. However, cancers are driven by both global and specific epigenomic dysregulation and the key is to restore the abnormal marks while retaining the normal distribution. We are now developing molecular tools for locus-specific epigenomic remodeling. As a member of the Siteman Cancer Center, Dr. Challen is dedicated to a career in academic cancer research.
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