Yingshi Ouyang, PhD
Research Assistant Professor, Magee-Womens Research Institute
I’m fascinated by our recent findings, indicating that nano-sized lipid vesicles are released by the human placenta into the maternal blood, and communicate key messages that are crucial for pregnancy health. We seek to understand how these vesicles target maternal tissues and execute their functions, such as antiviral response.
Yingshi Ouyang, PhD
Research in Brief
My research centers on the biology of human placenta. The placenta plays a central role in maternal-fetal gas exchange, transfer of nutrients and waste, hormone production and immunological defense. The placenta also communicates signals that are essential for pregnancy health. Accordingly, the human villous trophoblast layer, which includes syncytiotrophoblast that is directly bathed in maternal blood, regulates the release of these communication messages into the maternal circulation. In addition to hormones, growth factors, and other signaling proteins, the syncytiotrophoblast releases a repertoire of lipid-encapsulated extracellular vesicles (EVs) into the maternal blood, including apoptotic cell-derived EVs, microvesicles and nano-sized exosomes. I have recently uncovered that trophoblastic exosomes exhibit the strongest antiviral activity among the EVs. Consistently, plasma exosomes derived from pregnant women recapitulate the antiviral effect of trophoblastic exosomes. I currently pursue the trafficking and functions of trophoblastic exosomes. We aim to identify the tissues and cell types that are preferentially targeted by trophoblastic exosomes and decode the factors that are critical for exosome recognition and internalization. Our group has also shown that trophoblastic exosomes harbor microRNAs (miRNAs) that are expressed from the primate-specific chromosome 19 miRNA cluster (C19MC). These trophoblastic C19MC miRNAs can confer resistance to viral infection to non-placental cell types through the promotion of autophagy. We aim to identify mRNA transcripts that are directly targeted by C19MC miRNAs that may explain their biological functions, particularly the C19MC-mediated antiviral effects.
- Bayer, A., Lennemann, N. J., Ouyang, Y., Sadovsky, E., Sheridan, M. A., Roberts, R. M., Coyne, C. B., Sadovsky, Y. (2018) Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling. Placenta 61, 33-38.
- Wu, M., Ouyang, Y., Wang, Z., Zhang, R., Huang, P. H., Chen, C., Li, H., Li, P., Quinn, D., Dao, M., Suresh, S., Sadovsky, Y., Huang, T. J. (2017) Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci USA 114, 10584-10589.
- Ouyang, Y., Bayer, A., Chu, T., Tyurin, V.A., Kagan, V.E., Morelli, A.E., Coyne, C.B., and Sadovsky, Y. (2016). Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity. Placenta 47, 86-95.
- Bayer, A., Lennemann, N.J., Ouyang, Y., Bramley, J.C., Morosky, S., Marques, E.T., Jr., Cherry, S., Sadovsky, Y., and Coyne, C.B. (2016). Type iii interferons produced by human placental trophoblasts confer protection against zika virus infection. Cell Host Microbe 19, 705-712.
- Mouillet, J.F., Ouyang, Y., Coyne, C.B. and Sadovsky, Y. (2015) MicroRNAs in placental health and disease. American journal of obstetrics and gynecology. 213(4 Suppl): S163-72.
- Ouyang, Y., Mouillet, J. F., Coyne, C. B., and Sadovsky, Y. (2014) Placenta-specific microRNA in exosomes: good things come in nano-packages. Placenta 35, S69-73.
- Delorme-Axford, E., Donker, R.B., Mouillet, J.F., Chu, T., Bayer, A., Ouyang, Y., Wang, T., Stolz, D.B., Sarkar, S.N., Morelli, A.E., Sadovsky, Y., and Coyne, C.B. (2013) Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci USA 110, 12048-12053.
- Ouyang, Y., Petritsch, C., Wen, H., Jan, L.Y., Jan, Y. N., and Lu, B. (2011) The Caspase Dronc exerts a non-apoptotic function to restrain phospho Numb-induced ectopic neuroblast formation in Drosophila. Development 138, 2185-2196.
- Wang, H. *, Ouyang, Y. *, Somers, W. G., Chia, W., and Lu, B. (2007) Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449, 96-100. *equal contribution
- Ouyang, Y., Tu, Y., Barker, S. A., and Yang, F. (2003) Regulators of G-protein Signaling (RGS) 4, insertion into model membranes and inhibition of activity by phosphatidic acid. Journal of Biological Chemistry 278, 11115-11122.