Yukiko Sugi, Ph.D.
Research Associate Professor
Room 635, Basic Science Building
Office: (843) 792-6501
Lab: (843) 792-4603
Education:DVM Veterinary Medicine Yamaguchi University 1977
MS Veterinary Science Yamaguchi University 1979
PhD Cell Biology Saitama Medical School (Dr. R. Hirakow) 1986
Postdoctoral Fellow, Medical College of Wisconsin (Dr. J. Lough)
Research in the Sugi laboratory focuses on cardiac development using genetically engineered mouse models, primary cell cultures and in ovo whole chick embryo cultures with cellular and molecular biological approaches. The current research focus of the Sugi laboratory is endocardial cushion remodeling (Fig. 1) and prevalvular fibroblast differentiation (Fig. 2) that are critical developmental events for four-chambered heart formation and valvuloseptal morphogenesis. Valvuloseptal defects are among the most common and serious of congenital heart defects (CHDs). Mesenchymalized endocardial cushions undergo distal outgrowth, fusion and remodeling into membranous septum and atrioventricular (AV) valves. Failure of these processes results in several human CHDs. Despite the clinical relevance, the mechanisms governing how mesenchymalized AV cushions remodel into normal membranous septum and valves have only begun to be elucidated. The Sugi laboratory has shown that BMP signaling constitutes one component of the multiple pathways that regulate formation and maturation of AV endocardial cushions (Sugi et al., 2004; Okagawa et al., 2007; Inai et al., 2008; 2013). The Sugi laboratory currently focuses on elucidating cellular and molecular biological mechanisms by which BMP-2 signaling regulates endocardial cushion cell differentiation into prevalvular fibroblasts by interacting with molecules in other regulatory pathways. The significance of our research project is the combined experimental approach using mouse molecular genetics (Fig. 3), 3-D in vitro cell cultures (Fig. 4) and chick in ovo manipulation with gene transfer (Fig. 5).
- AHA 15GRNT25710305; Cell autonomous regulation by BMP2 in endocardial lineage for formation of valve and membranous septal progenitor cells. Y. Sugi, Principal Investigator.
- P20GM103499: BMP-Notch interaction in AV endocardial cushion remodeling and prevalvular fibroblast differentiation. Y. Sugi, Principal Investigator.
Education Interests and Activities:
- Undergraduate Mentoring: The Sugi laboratory hosts undergraduate students for their Independent Study and Bachelors Essay research projects. The Sugi laboratory also welcomes undergraduate students in the MUSC Student Undergraduate Research Program (SURP).
- Master Students: The Sugi laboratory welcomes motivated students in the master’s program. Positions are available for the students in participating in the ongoing research projects on cardiovascular development. Prior commitment in the cardiovascular research is not required.
- MCBP 762, Mechanisms of Development (Developmental Biology, Stem Cells and Animal Models): Sugi, Y., Course Director. This course will provide a general overview of fundamental developmental mechanisms focused on a comparison of different model organisms. This course covers early and intermediate developmental events (gastrulation and cardiovascular), stem cell biology, mouse molecular genetics and gene regulation, perinatal maturation through induction of stemness in differentiated adult cells and regenerative medicine. Comparative systems discussed include Drosophila, zebrafish, Xenopus, chick, mouse models and humans.
- Member of CGS Curriculum Committee
Selected Publications (* denote corresponding authorship. Total of over 2024 citations.
- Saxon JG, Baer DR, Barton JA, Hawkins T, Wu B, Trusk TC, Harris SE, Zhou B, Mishina Y, Sugi Y. BMP2 expression in the endocardial lineage is required for AV endocardial cushion maturation and remodeling. Dev Biol. 2017, Aug 5 PMID: 28790014 doi:10.1016/j.ydbio.2017.08.008
- Harikrishnan K, Cooley MA, Sugi Y, Barth JL, Rasmussen LM, Kern CB, Argraves KM, Argraves WS. Fibulin-1 suppresses endothelial to mesenchymal transition in the proximal outflow tract. Mech Dev. 2015 Jan 6. pii: S0925-4773(14)00091-4. doi: 10.1016/j.mod.2014.12.005. [Epub ahead of print] PMID: 25575930
- Ashraf H, Pradhan L, Chang EI, Terada R, Ryan NJ, Briggs LE, Chowdhury R, Zárate MA, Sugi Y, Nam HJ, Benson DW, Anderson RH, Kasahara H. A mouse model of human congenital heart disease: high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation. Circ Cardiovasc Genet. 2014 Aug;7(4):423-33. PMID: 25028484
- Inai K, Burnside JL, Hoffman S, Toole BP, Sugi Y*. BMP-2 Induces Versican and Hyaluronan That Contribute to Post-EMT AV Cushion Cell Migration. PLoS One. 2013 Oct 11;8(10):e77593. doi: 10.1371/journal.pone.0077593. PMID: 24147033
- Sugi, Y*., Kern, M. J., Markwald, R. R. and Burnside, J. L. Periostin expression is altered in aortic valves in Smad6 mutant mice. J. Neonatal Biol. 1: 101 2012. PMID: 25383261 [PubMed]
- Little, T. S., Mironov, V., Mehesz, A. N., Markwald, R., Sugi, Y., Lessner, S. M., Sutton, M. A., Liu, X., Wang, Q., Yang, X., Blancet, J. O., Skilets, M. Engineering a 3D, biological construct: representative research in the South Carolina project for organ biobabrication. Biofabrication, 3: 030202, 2011. PMID: 21926458 [PubMed - indexed for MEDLINE]
- Norris R. A., Moreno-Rodriguez R. A., Sugi, Y., Hoffman, S., Amaos, J., Hart, M. M., Potts, J. D., Goodwin, R. L., Markwald, R. R. Periostin regulates atrioventricular valve maturation. Dev Biol. 316, 200-213, 2008.
- Inai, K, Norris, R. A., Hoffman, S., Markwald, R. R., Sugi, Y*. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev. Biol. 315, 383-396, 2008.
- Okagawa, H., Markwald, R. R., Sugi, Y*.Functional BMP receptor in endocardial cells is required in atrioventricular cushion mesenchymal cell formation. Dev. Biol. 306: 179-192, 2007.
- Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, Trusk T, Potts JD, Goodwin RL, Davis J, Hoffman S, Wen X, Sugi, Y, Kern CB, Mjaatvedt CH, Turner DK, Oka T, Conway SJ, Molkentin J, Forgacs G, Markwald RR. Periostin regulates collagen I fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101: 695-711, 2007.
- Sugi, Y.*, Yamamura, H., Okagawa, H., Markwald, R. R. Bone Morphogenetic Protein-2 can mediate myocardial regulation of atrioventricular cushion mesenchymal cell formation in mice. Dev. Biol. 269: 505-518, 2004.
- Sugi, Y.*, and Markwald, R. R. Endodermal growth factors promote formation and assembly of endocardial angioblasts derived from the heart forming fields. Dev.Biol.,2003.263: 35-49. 2003.
- Sugi, Y.*, Naoki Ito, Gyorgyi Szebenyi, Kioina Myers, John F. Fallon, Takashi Mikawa and R. R. Markwald. Fibroblast growth factor (FGF)-4 can induce proliferation of cardiac cushion mesenchymal cells. Dev. Biol. 258: 252-263, 2003.
- Twal, W.O., Czirok, A., Hegedus, B., Knaak, C., Chintalapudi, M.R., Okagawa, H., Sugi, Y, and Argraves, W.S. Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. J. Cell Sci. 114: 4587-4598, 2001.
- Lough, J. and Sugi, Y. Endoderm and Heart Development. Dev. Dyn. 217: 327-342, 2000.
- Ramsdell, A. F., Moreno-Rodriguez, R.A., Weinecke, M. M., Sugi, Y., Turner, D. K.,
- Mjaatvedt, C. H. and Markwald, R. R. Identification of an autocrine signaling pathway that amplifies induction of endocardial cushion tissue in the avian heart. Acta Anat 162: 1-15, 1998.
- Markwald, R., C. Eisenberg, L. Eisenberg, T. Trusk and Y. Sugi. Epithelial mesenchymal transformations in early avian heart development. Acta Anatomica, 156: 173-186, 1996.
- Lough, J., M Barron, M. Brogley, Y. Sugi, D. L. Bolender, and X. Zhu. Combined BMP-2 and FGF-4, but neither factor alone, induce cardiogenesis in non-precardiac embryonic mesoderm. Dev. Biol. 178:198-202, 1996.
- Sugi, Y.* and Markwald, R.R. Formation and early morphogenesis of endothelial precursor cells and the role of endoderm. Dev. Biol. 175: 66-83, 1996.
- Sugi, Y.* and Markwald, R.R. Early endocardial formation from precardiac mesoderm as revealed by QH-1 antibody staining. It. J. Anat. Embryol. 100: 263-272, 1995.
- Byeon, M.K., Sugi, Y., Markwald, R.R. and Hoffman, S. NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain. J. Cell Biol. 128: 209-221, 1995.
- Sugi, Y. and Lough, J. Activin-A and FGF-2 mimic the inductive effects of anterior endoderm on terminal cardiac myogenesis in vitro. Dev. Biol. 168: 567-574, 1995.
- Sugi, Y., Sasse, J., Barron, M. and Lough, J. Developmental expression of fibroblast growth factor receptor-1 (cek-1, flg) during heart development. Dev. Dyn. 202: 115-125, 1995.
- Sugi, Y. and Lough, J. Anterior endoderm is a specific effector of terminal cardiac myocyte differentiation in cells from the embryonic heart forming region. Dev. Dyn. 200: 155-162, 1994.
- Sugi, Y., Sasse, J. and Lough, J. Inhibition of precardiac mesoderm cell proliferation by antisense oligodeoxynucleotide complementary to fibroblast growth factor-2 (FGF-2). Dev. Biol. 157:28-37, 1993.
- Sugi, Y. and Lough, J. Onset of expression and regional deposition of alpha-smooth and sarcomeric actins during avian heart development. Dev. Dyn. 193:116-124, 1992.
- Sugi, Y.* and Hirakow, R. Cytoskeletal filaments in embryonic chick myocardial cells as revealed by the quick-freeze deep-etch method combined with immunocytochemistry. Cell Tissue Res. 263:459-469, 1991.
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