Postdoctoral Fellow
Division of Hematology, Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
I am Kiwon Lee working with Dr. Mortimer Poncz in the Division of Hematology at the Children's Hospital of Philadelphia. In my Ph.D., I studied with Dr. Kwon in South Korea on the role of the large-scale chromatin architectures in gene regulation. To explore my knowledge of chromatin biology during hematopoiesis, I joined Dr. Gerd Blobel’s laboratory as a postdoctoral fellow at the Children’s Hospital of Philadelphia. I focused on studying dynamic enhancer looping structures and the functional relationship with transcription regulation in hematopoiesis. In this study, I discovered that an enhancer stably contacts a cognate promoter region but also dynamically contacts through its gene body as transcription elongation progresses. This study contributes to the understanding of three-dimensional chromatin structures and transcription mechanisms at the c-Kit locus, one of the master transcription regulators, during hematopoiesis. Since I joined Dr. Mortimer Poncz's laboratory as a research associate, my research interest has shifted to translational applications in how the defects in key transcriptional regulators such as RUNX1 can affect lineage-specific differentiation and cancer development. It has been well known that heterozygous defects in RUNX1 are responsible for a familial platelet disorder with associated myeloid malignancy (FPDMM) and an increased risk of myelodysplasia and acute myeloblastic leukemia. However, since animal models do not recapitulate some of the phenotypes of FPDMM, my colleagues and I focus on establishing a human CD34-derived ex-vivo megakaryopoiesis system in RUNX1depletion and developing a mouse-human hybrid model by xenotransplantation of human CD34-HSPC into immunocompromised mice. These ex-vivo and in-vivo model systems may be useful preclinically for drug testing before committing to a clinical trial to correct phenotypes of FPDMM.