Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Embryo implantation marks the beginning of direct interaction between fetus and mother. However, the underlying mechanism that regulates this biological process is not well defined. In fact, about 15% of couples have difficulty conceiving and need to seek fertility treatment. However, even if good-quality embryos are transferred, about 75% of women fail to conceive or give birth, partly due to implantation failure. It is believed that the maternal reproductive tract changes its microenvironment by secreting various factors or macromolecules and expressing adhesion molecules or surface receptors to provide the best conditions for embryo implantation and maintenance of pregnancy. Currently, no known molecules/compounds can increase the embryo implantation rate.
Small molecules are chemical compounds with a therapeutic activity that can easily bind to or enter cells. Recently, we established a high-throughput screening method by using a spheroid-endometrial co-culture assay with receptive and non-receptive human endometrial epithelial cells and screened more than 1000 small molecules and identified over 100 small molecules that significantly suppress or stimulate spheroid attachment onto human endometrial Ishikawa cells. We hypothesized that the LOPAC modulates could be used to suppress and/or stimulate spheroid (embryo surrogate) attachment through modulating endometrial receptivity in vitro and in vivo.
We will test our hypothesis with the following objectives: (1) The use of receptive and non-receptive endometrial epithelial cells to validate putative small molecules that modulate endometrial receptivity, (2) Investigate the synergistic effect of the small molecules on endometrial epithelial and stromal cell functions, and (3) Perform comparative proteomic and metabolomics analysis of endometrial protein expression and secretion: in vitro and in vivo studies. Results from this study will provide essential information on the selected small molecules in regulating the implantation process, delineating the underlying signaling mechanism modifying the expression of membrane protein(s) and/or secretome profiles for embryo attachment, and validate the potential pre-clinical application of these small molecules using in vivo mouse models.
Dr CKF Lee, Department of Obstetrics and Gynaecology
Dr. Lee got his Ph.D. in Biochemistry from the Chinese University of Hong Kong and trained in postdoctoral training at Tufts University, Massachusetts, USA. He joined the Department of Obstetrics and Gynaecology at The University of Hong Kong as a Research Assistant Professor in 1998 and was promoted to Associate Professor in 2008. He was Past-President of the Hong Kong Society for Reproductive Medicine, and the Hong Kong Society of Endocrinology, Metabolism, and Reproduction. He has published more than 90 original articles in international journals with an H index of 32 (total citation >3000). His students have obtained many international and local awards including ‘The Best Poster Award of Society for the Study of Reproduction (SSR) – Southeast Asia Region’.
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