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.
Histiocytic Disorders, Stem Cell Transplantation (blood disorders)
The Zambidis Lab
Zambidis E, Sinka L, Tavian M, Jokubaitis V, Simmons P, Péault B. Emergence of human angio-hematopoietic cells in normal development and from cultured embryonic stem cells, Ann NY Acad Sci 2007.1106: 223-32.
Zambidis E,Park TS, Yu W, Tam A, Levine M, Yuan X, Pryzhkova M, Péault B. Expression of ACE (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells, Blood, 2008.112: 3601-14.
Peters A, Burridge P, Levine M, Pryzhkova M, Park TS, Yuan X, Zambidis E. Challenges in generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells. Int. J. Developmental Biology, 2010.54: 965-90.
Ohm J, Mali P, van Nester L, Berman D, Liang L, Pandiyan K, Briggs K, Zhang W, Argani P, Sioms B, Zambidis E. Schuebel K, Cope L, Yen J, Cheng L, Baylin S. Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells, Cancer Res 2010.19: 7662-73.
Burridge PW, Thompson S, Millrod MA, Weinberg S, Yuan X, Tung L, Zambidis E. A universal protocol for highly efficient cardiac differentiation of human pluripotent stem cells that eliminates interline variability. PLoS One 2011.6(4): e18293. doi:10.1371/journal.pone.0018293.
Thompson S, Burridge P, Lipke E, Zambidis E,Tung LT. Engraftment of human embryonic stem cell-derived cardiomyocytes improved conduction in an arrythmogenic in vitro model. J Mol Cell Cardiol 2012.53:15-23.
Park TS, Zimmerlin L, Zambidis E. Efficient and simultaneous generation of hematopoietic and vascular progenitors from human induced pluripotent stem cells. Cytometry A 2012.83:114-126. DOI: 10.1002/cyto.a.22090.
Park TS, Huo JS, Peters A, Talbot CC, Kaplan IM, Zambidis E. Growth factor-activated stem cell circuits and stromal signals cooperatively accelerate iPSC reprogramming of lineage-committed human myeloid progenitors, PLoS One 2012.7(8): e42838. DOI:10.1371/journal.pone.0042838.
Blazeski A, Zhu R, Hunter DW, Weinberg S, Zambidis E, Tung L. Electrophysiological and contractile function of cardiomyocytes derived from human embryonic stem cells. Prog. Biophys & Mol. Biology 2012.110(2-3):178-95.
Blazeski A, Zhu R, Hunter DW, Weinberg S, Zambidis E, Tung, L. Cardiomyocytes derived from human induced pluripotent stem cells for modeling normal and diseased cardiac electrophysiology and contractility. Prog. Biophys & Mol. Biology 2012.110(2-3):166-77.
Huo JS, Zambidis E. Pivots of pluripotency: the roles of non-coding RNAs in regulating embryonic and induced pluripotent stem cells. Biochim Biophys Acti 2012.1830(2): 2385-94.
Panicker LM, Miller D, Park TS, Patel B, Azevedo JL, Awad O, Masood AM, Veenstra TD, Goldin E, Polumuri SK, Vogel SN, Sidransky E, Zambidis ET, Feldman RA. (2012). Modeling Gaucher disease using human induced pluripotent stem (iPS) cells. Proc. Natl. Acad. Sci. USA 2012.109(44):18054-9.
Resar LMS, Sha SN, Kerr C, Cope L, Zambidis E, Belton A, Huso D. HMGA1 a factor enriched in hematopoietic stem cells, embryonic stem cells and hematologic malignancy enhances cellular reprogramming to a pluripotent stem-like cell, PLoS One 2012. 7(11):e48533.
Rufaihah AJ, Huang NF, Kim J, Herold J, Volz K, Park TS, Lee JC, Zambidis E, Reijo-Pera, R, Cooke JP. Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity, Am J Transl Res, 2013:5 (1): 21-35.
Park TS, Bhutto I, Zimmerlin L, Huo JS, Nagaria P, Miller D, Rufaihah AJ, Talbot C, Aguilar J, Grebe R, Merges C, Reijo-Pera R, Feldman RA, Rassool F, Cooke J, Lutty G, Zambidis ET. Vascular progenitors from cord blood-derived iPSC possess augmented capacity to regenerate ischemic retinal vasculature.Circulation 2014 Jan 21:129(3):359-72.
Gorospe G, Zhu R, Millrod MA, Zambidis ET, Tung L, Vidal R. Automated grouping of action potentials of embryonic stem cell-derived cardiomyocytes. 99: IEEE Trans. Biomed. Eng, 2014.
Panicker LM, Miller D, Awad O, Bose V, Lun Y, Park TS, Zambidis ET, Sgambato JL, Feldman RA. Gaucher iPSC-derived macrophages produce elevated levels of inflammatory mediators and serve as a new platform for therapeutic development. Stem Cells, 2014; doi: 10.1002/stem.1732.
Zimmerlin L, Park TS, Donnenberg VS, Zambidis E, Donnenberg AD. Pericytes: a ubiquitous source of adult tissue stem cells, in "Stem Cells in Aesthetic Procedures", edited by Melvin Shiffman, Springer, 2014 (Book Chapter).
Agarwal JR, Zambidis ET. Role of an NFkB-STAT3 signaling axis in the induction and maintenance of the pluripotent state, inPluripotent Stem Cell Biology - Advances in Mechanisms, Methods and Models, ed. Craig S Atwood and Sivan Vadakkadath Meethal, 2014, InTech (Book Chapter).
Park TS, Donnenberg VS, Donnenberg AD, Zambidis E, Zimmerlin L. Dynamic interactions between cancer stem cells and their stromal partners. Curr Pathobiol Rep 2014.2(1) 41-52.
Mahairaki V, Ryu J, Peters A, Park TS, Burridge PW, Talbot CC, Zambidis ET, Koliatsos VE. Virus-free induced pluripotent stem cells from familial Alzheimer’s disease patients differentiate into neurons with amyloidogenic properties. Stem Cells Dev 2014; 23(24): 2996-3010.
Huo JS, Baylin SB, Zambidis ET. Cancer-like epigenetic derangements of human pluripotent stem cells and their impact on applications in regeneration and repair. Curr Opin Genet Dev 2014; 28: 43-49.
Zhong X, Gutierrez C, Xue T,Hampton C, Vergara MN, Peters A,Zambidis E, Meyer J, Gamm DM, Yau KW, Canto-Soler MV. Generation of three-Dimensional retinal cups with mature functional photoreceptors from human iPSC, Nature Com, 2014.
Sgambato JA, Park TS, Miller D, Panicker LM, Sidransky E, Lun Y, Awad O, Zambidis ET, Feldman RA. Gaucher induced pluripotent stem cells display decreased erythroid potential and aberrant myelopoiesis, Stem Cells Transl Med, 2015 Aug;4(8):878-86.
Baizley F, Liu C, Yuan X, Hao H, All AH, De Los Angeles A,Zambidis ET, Gearhart JD, Kerr CL. Direct reprogramming of primordial germ cells into induced pluripotent stem cells. Stem Cells Dev 2015.Jul 8. [Epub ahead of print] doi:10.1089/scd.2015.0100.