Yukiko Sugi, PhD, Medical University of South Carolina
PROJECT TITLE: BMP-Notch interaction in AV endocardial Cushion Remodeling and prevalvular fibroblast differentiation
Valvuloseptal defects are among the most common and serious congenital heart defects (CHDs). Mesenchymalized AV endocardial cushions undergo distal outgrowth, fusion and remodeling into ventricular membranous septum and AV valves. Failure in these processes results in several human CHDs. Despite the clinical relevance, the mechanisms governing how mesenchymalized AV cushions mature and remodel into valves and membranous septum have only begun to be elucidated.
Results from proposed experiments should elucidate the embryonic mechanisms by which cushion mesenchymal cells differentiate into normal prevalvular fibroblasts, thereby enabling the potential development of innovative therapeutic interventions for one of the major forms of human CHDs.
SC INBRE DRP has provided significant resources to me. Originally trained as a developmental biologist utilizing the chick primary cell cultures, I have been able to extend my research program to an in vivo setting using mouse genetic approaches. This is an important step in my career development. By using the first two years of SC INBRE support, I have been able to successfully generate collaborations with extra-institutional investigators with outstanding expertise in mouse molecular genetics. As a result of these collaborations, I have generated genetically engineered mouse models for the first time in my research career and assembled data for a paper as a senior author, a paper which was accepted by a high standard journal, Developmental Biology.
Publications as a result of the project:
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
April 27, 2018