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I have three main areas of research interest, namely regulation of fertilization, microRNAs in reproduction and stem cells.
My interest on regulation of fertilization started with my identification of a novel glycoprotein, later named as glycodelin-F in the human follicular fluid that inhibited the binding of human spermatozoa with zona pellucida of oocytes. Later, we found another isoform of glycodelin in the human cumulus matrix that stimulated the binding. The difference in biological activities of glycodelin isoforms depend on their glycosylation, as all the glycodelin isoforms contain the protein core. We had also identified one of the receptors of glycodelin in human sperm responsible for the spermatozoa- zona pellucida binding (Chiu et al., 2007, J Cell Sci 120, 33-44), and in human trophoblast for modulating the invasiveness of the cells (Lam et al., 2011, J Biol Chem 286, 37118-27). Clinically, pathological change in the glycosylation of glycodelin as in gestation diabetes mellitus is associated with a change in the immunosuppressive activities of the amniotic isoform of glycodelin (Lee et al, 2011, Diabetes 60, 909-17). The results of glycodelins demonstrate the importance of glycosylation in spermatozoa-zona pellucida interaction. Therefore, we studied the glycan profile of human zona pelluida in collaboration with Professor A. Dell, Imperial College, London. The result showed that a high percentage of the glycans on the zona pellucida contained a structure known as sialy Lewis x, which when being blocked reduced the spermatozoa-zona pellucida binding by about 70% (Pang et al., 2011, Science 333, 1761-64).
The second research interest is on microRNAs in reproduction. We have recently provided the first evidence that microRNAs in spermatozoa are important for cleavage of the mouse zygotes (Liu et al., 2012, PNAS, 109, 490-4). We also showed that microRNAs in mouse preimplantation embryos modulate implantation (Liu et al., 2012, PLoS One, 7, e37039) and activation of dormant blastocysts (Cheong et al, 2014, Hum Reprod 2014 Jan 12 [Epub]).
The third research interest is on stem cells. We recently reported the presence of stem/progenitor cells in endometriotic tissue (Chan et al., 2011, Am J Pathol, 178, 2832-44). Our data show that microRNAs regulate the formation of stem cells. Sirt1 facilitates the formation of induced pluripotent stem cells from mouse fibroblasts and microRNA-34a is involved in the process (Lee et al., 2012, PLoS One, 7, e45633). Forced-expression of microRNA-135a induces cervical tumoriogenesis (Leung et al., 2014, Carcinogenesis accepted) and formation of cells with cancer stem cell-like properties.