Research Abstract:
We study molecular mechanisms that regulate blood (hematopoietic), blood vessel (endothelial) and cardiac cell lineage development. We utilize an in vitro differentiation model of pluripotent stem cells, such as embryonic stem (ES) and induced pluripotent stem (iPS) cells, and early mouse embryos to address self-renewal, lineage commitment, and differentiation. So far we have shown that hematopoietic cells, endothelial cells, smooth muscle cells and cardiomyocytes develop from a subset of mesoderm expressing Flk-1, a receptor tyrosine kinase (Flk-1 expressing mesoderm). We are currently investigating transcription factors that control the step-wise commitment from mesoderm to Flk-1 expressing mesoderm and from the Flk-1 expressing mesoderm to hematopoietic, endothelial, smooth muscle cells and cardiomyocytes. Additionally, we study stem cell regulation and maintenance in pathologic conditions by utilizing hematopoietic stem cells (HSC) as a model. We are currently characterizing HSC properties and HSC niches in a chronic inflammatory arthritic mouse model. Such characterization will be critical for understanding how stem cells are maintained and regulated in normal vs pathologic conditions. Our current projects include: 1) Transcriptional Control of Hematopoietic, Vascular and Cardiac Cell Lineage Development 2) Directed Differentiation and Application of Hematopoietic, Vascular and Cardiac Progenitors from Stem Cells 3) Somatic Cell Reprogramming 4) Hematopoietic Stem Cell Regulation in Chronic Inflammation
Selected Publications:
Lugus JJ*, Park C*, Ma YD and Choi K. Both primitive and definitive blood cells are derived from Flk1+ mesoderm. Blood 2009 113(3):563-566.
Ma YD*, Park C*, Zhao H, Oduro K, Tu X, Long F, Allen PM, Teitelbaum S and Choi K. Defects in osteoblast function with unaltered long term repopulating potential of hematopoietic stem cells in mice undergoing chronic inflammatory arthritis. Blood. 2009 (In Press).
Lee D, Park C, Lee H, Lugus JJ, Kim SH, Arentson E, Chung YS, Gomez G, Kyba M, Lin S, Janknecht R, Lim DS and Choi K. ER71 acts downstream of BMP, Notch and Wnt signaling in blood and vessel progenitor specification. Cell Stem Cell 2008 2:497-507.
Lugus JJ, Chung YS, Mills J, Kim S, Grass F, Kyba M, Doherty J, Bresnick EH and Choi K. GATA-2 functions at multiple steps in hemangioblast development and differentiation. Development 2007 134:393-405.
Park C, Lavine K, Mishina Y, Deng CX, Ornitz DM and Choi K. Bone Morphogenetic Protein Receptor IA signaling is essential for vascular development and atrioventricular endocardial cushion formation, but not for hematopoietic development. Development 2006 133: 3473-3484.
Last Updated: 09/10/2009 |