The Zambidis lab is interested in the developmental biology of normal and malignant human stem cells. His group employs genetic manipulation and differentiation of human embryonic and induced pluripotent stem cells (iPSC) to study the cellular and molecular mechanisms of human hematopoiesis, vasculogenesis, and cardiogeneisis. Using human embryonic stem cells (hESC) derived from both normal and preimplantation genetic diagnosis (PGD)-screened embryos, as well as human iPSC, he is exploring how early mesodermal progenitors and human hemangioblast (bi-potential progenitor of hematopoietic stem cells (HSC) and endothelium) may give rise to the entire human hematopoietic and vascular systems, and whether such progenitors can be derived and expanded from differentiating human iPSC. His laboratory is studying the role of a variety of proteins and signaling molecules that are critically important in orchestrating the initiation of human embryonic hematopoiesis by directing the formation of human hemato-vascular progenitors in hESC and hiPSC. hESC/hiPSC-derived blood progenitors are also important in the understanding of the developmental origins of pediatric leukemia, but also for clinical HSC transplantation. Another major area of focus is determining the shared molecular circuits that regulate both malignant transformation and the maintenance of pluripotency. Applying these principles of shared biology between hematopoietic stem-progenitors and pluripotent stem cells, his group recently accomplished the creation of improved, highly efficient methods for generating nonintegrated, non-viral human induced pluripotent stem cell (hiPSC) lines from myeloid progenitors that possess enhanced differentiation capacities and rapid loss of epigenetic memory. Additional projects include studying the developmental biology of gastrulation and cardiogenesis in model organisms and explores potential applications of pluripotent stem cell-derived cardiac in tissue engineering, regenerative medicine, cardiotoxicity screening and novel drug discovery.
- Zambidis, E.T.; Oberlin, E.; Tavian, M.; Peault, B. Blood-forming endothelium in human ontogeny: lessons from in utero development and embryonic stem cell culture. Trends in cardiovascular medicine. 2006 Apr;16(3):95-101.
- Shah, N.; Zambidis, E.T. False-photosensitivity and transient hemiparesis following high-dose intravenous and intrathecal methotrexate for treatment of acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009 Jul;53(1):103-105.
- Ohm, J.E.; Mali, P.; Van Neste, L.; Berman, D.M.; Liang, L.; Pandiyan, K.; Briggs, K.J.; Zhang, W.; Argani, P.; Simons, B.; Yu, W.; Matsui, W.; Van Criekinge, W.; Rassool, F.V.; Zambidis, E.; Schuebel, K.E.; Cope, L.; Yen, J.; Mohammad, H.P.; Cheng, L.; Baylin, S.B. Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells. Cancer Res. 2010 Oct 1;70(19):7662-7673.
- Peters, A.; Burridge, P.W.; Pryzhkova, M.V.; Levine, M.A.; Park, T.S.; Roxbury, C.; Yuan, X.; Peault, B.; Zambidis, E.T. Challenges and strategies for generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells. Int J Dev Biol. 2010;54(6-7):965-990.
- Pryzhkova, M.V.; Peters, A.; Zambidis, E.T. Erythropoietic differentiation of a human embryonic stem cell line harbouring the sickle cell anaemia mutation. Reprod Biomed Online. 2010 Aug;21(2):196-205.
The Zambidis Lab