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Biography

Dr. Fabiana Perna earned her MD from University of Naples Federico II, Italy and completed her residency in Hematology. As a member in the laboratory of Dr. Stephen Nimer, at Memorial Sloan Kettering Cancer Center in New York, Dr. Perna obtained her PhD, investigating the epigenetic regulation of transcription in hematopoiesis. Through these studies, she contributed to elucidating the function of several chromatin-related proteins in affecting the proliferation and lineage differentiation potentials of hematopoietic and pluripotent stem cells, and the signaling pathways regulating their properties. She was awarded the American Society of Hematology Scholar Award in 2012, the ASH/EHA Translational Research Training in Hematology, the American Italian Cancer Foundation Research Fellowship and the Memorial Sloan Kettering Cancer Center Clinical Fellowship. She is now a Research Associate in the laboratory of Dr. Michel Sadelain, Director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center, New York

Abstract

Epigenetic regulation of key transcriptional programs is a critical mechanism of hematopoietic development and, aberrant epigenetic patterns and mutations frequently occur in hematologic malignancies perturbing hematopoietic stem cells. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of smad5 and impairing its recruitment to target regulatory regions. Indeed, knock-down of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. Furthermore, we found that regulation of smad5 targets by L3MBTL1 also occurs in mature hematopoietic cell populations, affecting erythroid differentiation. Altogether, these findings define an epigenetic mechanism underlying priming of hematopoietic-specific transcriptional networks and provide rationale for development of therapeutic approaches for patients with anemia.