Yoel Sadovsky, MD
Executive Director, Magee-Womens Research Institute, Elsie Hilliard Hillman Chair of Women’s Health Research, Distinguished Professor of OB-GYN, Microbiology and Molecular Genetics, Vice Chair (research), Department of OB-GYN and Reproductive Sciences, Associate Dean, Women's Health Research and Reproductive Sciences, University of Pittsburgh
We seek to understand the early phases of human development: how the fetus grows, matures, and interacts with its lifeline - the placenta and maternal environment. These formative steps during the 9 months of pregnancy set the stage for 90+ years of health, wellness, and therefore, the future of humankind.
Yoel Sadovsky, MD
Research in Brief
The placenta at the feto-maternal interface fulfills functions that are critical for intrauterine development, including gas exchange, supply of nutrients, removal of waste products, endocrine regulation, and immunological and physical defense. Our lab utilizes molecular and cellular approaches to decipher mechanisms underlying placental development, differentiation of placental (trophoblast) cells, and their response to injury. We focus on three major areas:
- Placental non-coding RNAs: We use diverse technologies to define the function and regulation of trophoblastic microRNA and long non-coding RNA in response to injuries, such as hypoxia and viral infections.
- Extracellular vesicles at the maternal-placental-fetal interface: We interrogate the mechanisms of release, uptake and function of placental exosomes and other extracellular vesicles.
- Placental lipidomics: We focus on fat trafficking in the feto-placental unit, including the dynamics of lipid droplets and trophoblastic mobilization of fatty acids. We also investigate the function of oxidized phospholipids, which may lead to trophoblast injury, including ferroptotic death.
Using cultured primary human placental cells, genetically-altered mice, and placental samples from normal or pathological human pregnancies, we examine molecular mechanisms underlying trophoblast response to diverse stressors that adversely influence the homeostatic balance between cell injury and adaptation. These stressors contribute to placental dysfunction that underlies diseases such as fetal growth restriction, which predispose to childhood neurodevelopmental dysfunction and adult metabolic syndrome.
Current Lab Funding
- Acoustofluidic Separation of Placental Nanovesicle Subpopulations in Obstetrical Diseases (Co-PIs: Y Sadovsky, T Huang), NIH/NICHD R01HD103727, (2021-2026)
- Exosome Based Placental Maternal Communication (PI: Y Sadovsky), NIH/NICHD R37HD086916, (2017–22).
- Placental Extracellular Vesicles as Regulators of Maternal Adaptive Immunity (Co-PIs: Morelli, Sadovsky), NIH/NIAID R01AI148690 (2019-2024).
- Technologies and Interventions to Reduce Risks of Infant Mortality in Prenatal and Postnatal Care (PD, Project PI: Yoel Sadovsky), Richard King Mellon Foundation (2019-2024).
- Placental Cell Defense (PI: Y Sadovsky), 25 Club of Magee-Womens Hospital, (2021).
- The Role of the Placenta in Preterm Birth, (PI: Y Sadovsky), Margaret Ritchie R. Battle Family Charitable Fund, (2017–21)
Recent Lab Funding
- Extracellular Vesicles and Their ncRNA cargo as Markers of Trophoblast Injury (PI: Y Sadovsky), NIH/NICHD R01HD086325, (2015–20).
- The Regulatory Code Governing Placenta-specific Expression of the Chromosome 19 miRNA Cluster (Co-PIs: Y Sadovsky, JF Mouillet) NIH/NICHD R21HD089732, (2016–19).
- Primary Human Trophoblasts and the Transfer of Viral Resistance (Co-PIs: Y Sadovsky, C Coyne), NIH/NICHD R01HD075665 (2012-2017).
- March of Dimes Transdisciplinary Research Center for Preterm Birth at the Univ. of Pennsylvania (PD: D Driscole, Project PI: Y Sadovsky), March of Dimes 22-FY14-487 (2014-2019).
- Adaptive Signals Emanating from the Injured Placenta, (PI: Y Sadovsky), 25 Club of Magee-Womens Hospital, (2018-20).
Services & Protocols
Isolation of primary human trophoblasts (PHTs) from the term placenta
Laboratory protocol for PHT isolation. Described also in:
- Nelson DM et al, Am J Obstet Gynecol 1999;180:896e902 (PUBMED http://www.ncbi.nlm.nih.gov/pubmed/?term=Am+J+Obstet+Gynecol+1999%3B180%3A896e902)
- Schiaff WT et al, J Clin Endocrinol Metab 2000 (PUBMED http://www.ncbi.nlm.nih.gov/pubmed/11061552)
- Sadovsky Y, Caughey AB, DiVito M, D’Alton ME, Murtha AP, Society for Maternal-Fetal Medicine Research Committee. Research to knowledge: Promoting the training of physician-scientists in the biology of pregnancy (SMFM Special Statement). Am J Obstet Gynecol 2018;281(1):B9-B13. https://www.ncbi.nlm.nih.gov/p...Bilidirici
- I, Schaiff WT, Chen B, Morizane M, Oh SY, O’Brien M, Sonnenberg-Hirche C, Chu T, Barak, Y, Nelson DM, Sadovsky Y. PLIN2 is essential for trophoblastic lipid droplet accumulation and cell survival during hypoxia. Endocrinology 2018;159(12):3937-49. https://www.ncbi.nlm.nih.gov/pubmed/30351430
- Mouillet JF, Chu T, Nelson DM, Mishima T,Sadovsky Y. MiR-205 silences MED1 in hypoxic primary human trophoblasts. FASEB J 2010;24(6):2030-9. http://www.ncbi.nlm.nih.gov/pubmed/20065103
- Delorme-Axford E, Donker RB, Mouillet JF, Chu T, Bayer A, Ouyang Y, Wang T, Stolz DB, Sarker SN, Morelli AD, Sadovsky Y*, Coyne CB*.. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci USA 2013;110(29):12048-53. PMID23818581 (*equal contribution) Recommended by Faculty of 1000, August 2013. 2013 Cozzarrelli Prize recipient, Proceedings of the National Academies of Sciences. http://www.ncbi.nlm.nih.gov/pubmed/23818581
- Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Azevedo Marques TE, Jr, Cherry S, Sadovsky Y*, Coyne CB*. Type III interferions produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 2016;113(19):E2598-607. (*equal contribution) https://www.ncbi.nlm.nih.gov/pubmed/27066743
- Mishima T, Sadovsky E, Gegick M, Sadovsky Y. Determinants of effective lentivirus-drive microRNA expression in vivo. Sci Rep 2016;6:33345. https://www.ncbi.nlm.nih.gov/pubmed/27627961
- Chang G, Mouillet JF, Mishima T, Chu T, Sadovsky E, Coyne CB, Parks WT, Surti U, Sadovsky Y. The expression and trafficking of placental microRNAs at the feto-maternal interface. FASEB J 2017;31(7):2760-70. https://www.ncbi.nlm.nih.gov/pubmed/28289056
- 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 TJ*. Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci USA, 2017;114(40):10584-9. (*equal contribution) https://www.ncbi.nlm.nih.gov/pubmed/28923936
- Li H, Pinilla-Macua I, Ouyang Y, Sadovsky E, Kajiwara K, Sorkin A, Sadovsky Y. Internalization of trophoblastic small extracellular vesicles and detection of their miRNA cargo in P-bodies. J Extracell Vesicles 2020;9(1):1812261. https://pubmed.ncbi.nlm.nih.gov/32944196/
- Beharier O, Tyurin VA, Goff JP, Guerrero-Santoro J, Kajiwara K, Chu T, Tyurina YY, St Croix C, Wallace CT, Parry S, Parks WT, Kagan VE, Sadovsky Y, PLA2G6 guards placental trophoblast against ferroptotic injury. Proc Natl Acad Sci USA 2020;117(44):27319-27328. https://pubmed.ncbi.nlm.nih.gov/33087576/
For additional publications, visit Pubmed.