Yoel Sadovsky, MD
Executive Director, Magee-Womens Research Institute, Elsie Hilliard Hillman Chair of Women’s Health Research, Distinguished Professor of OBGYN, Microbiology and Molecular Genetics, Vice Chair (research) Department of OBGYN and Reproductive Sciences, Associate Dean, Women's Health Research and Reproductive Sciences, University of Pittsburgh
The trophoblast at the feto-maternal interface fulfills functions that are critical for embryonic development, including gas exchange, supply of nutrients, removal of waste products, endocrine regulation, and immunological defense. The Sadovsky lab utilizes molecular and cellular approaches to decipher mechanisms underlying placental development and differentiation. We focus on three major areas:
- Placental microRNAs and response to injuries: We use diverse technologies to define the function and regulation of trophoblastic miRNA in response to injuries, such as hypoxia and viral infections.
- Placental lipidomics: We focus on fat trafficking in the feto-placental unit, including the dynamics of lipid droplets and trophoblastic mobilization of fatty acids and neutral lipids, and their role in placental pathobiology and in the mechanisms underlying preterm birth.
- Trophoblast differentiation: We seek to understand the fundamental mechanisms that underlie trophoblast differentiation, fusion, and their role in placental adaptation to injury
Using cultured primary human placental cells, genetically-altered mice, and placental samples from abnormal human pregnancies, the lab examines molecular mechanisms underlying trophoblast response to diverse stressors that adversely influence the homeostatic balance between cell injury and regeneration. These stressors contribute to placental dysfunction and fetal growth restriction (FGR), which predispose to childhood neurodevelopmental dysfunction and metabolic derangements in the adult.
- 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, in press, epub available. https://www.ncbi.nlm.nih.gov/pubmed/28289056
For additional publications, see: http://www.ncbi.nlm.nih.gov/sites/myncbi/yoel.sadovsky.1/collections/47374913/public/
Services & Protocols
TGenerator is an executable program to incorporate a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates in analysis of high-density DNA microarrays. Described in Budhraja et al, BMC Biology 2003, 1:1.
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)