Hewitt Lab

Our research group investigates mechanisms that guide physiological and regenerative blood formation. We are especially absorbed with understanding how gene regulation is controlled during the differentiation of all the varied cell types that exist in the blood system, the role of the GATA family of transcription factors in development, and diseases that arise from deregulated transcription factor activities including chronic anemias and leukemias. 

Among the ongoing projects in the lab:

• The Sterile Alpha Motif-14 (SAMD14)locus contains a GATA2-regulated enhancer (Samd14-Enh) that drives its expression in anemia, with relevance to stem cell homeostasis, anemia, hematopoietic/erythropoietic stress, and the cardiovascular system more broadly. We are working towards a general model to describe Samd14 activities and its cognate transcriptional enhancer in hematopoietic stem/progenitor cells.
• While SAM proteins are involved in many cell processes, no general principles have emerged to explain many SAMs in the human proteome, whether SAM domains can substitute for others, and what features confer functional properties this poorly studied family of protein domains in hematologic disease. We are defining new functions for SAM proteins in transcription and cell signaling.
• Mutations in coding and noncoding regions of the transcription factor GATA2 cause a diverse range of adverse phenotypes, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), primary immunodeficiencies, and aplastic anemia. We use ranked prioritization approaches and CRISPR/Cas9 gene editing to test non-coding DNA element function in cells and animals.

Full list of publications.