Yoel Sadovsky, MD
Director, Magee-Womens Research Institute, Elsie Hilliard Hillman Chair of Women’s Health Research, Professor of Obstetrics, Gynecology and Reproductive Sciences, and Microbiology and Molecular Genetics, and CTSI
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.
Mariani TJ, Budhraja V, Mecham BH, Gu CC, Watson MA, Sadovsky Y. A variable fold change threshold determines significance for expression microarrays. FASEB J2003;17(2):321-3. http://www.ncbi.nlm.nih.gov/pubmed/12475896
- Yan X, Mouillet JF, Ou Q, Sadovsky Y. A novel domain within the DEAD-box protein DP103 is essential for transcriptional repression and helicase activity. Mol Cell Biol2003;23(1):414-23. http://www.ncbi.nlm.nih.gov/pubmed/12482992
- Budhraja V, Spitznagel E, Schaiff WT, Sadovsky Y. Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays. BMC Biol2003;1:1. http://www.ncbi.nlm.nih.gov/pubmed/14641937
- Mouillet JF, Sonnenberg-Hirche C, Yan X, Sadovsky Y. p300 regulates the synergy of steroidogenic factor-1 and early growth response-1 in activating luteinizing hormone-beta subunit gene. J Biol Chem 2004;279(9):7832-9. http://www.ncbi.nlm.nih.gov/pubmed/14681221
- Chen B, Nelson DM, Sadovsky Y. N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury. J Biol Chem 2006;281(5):2764-72. http://www.ncbi.nlm.nih.gov/pubmed/16314423
- Schaiff WT, Knapp FF, Jr., Barak Y, Biron-Shental T, Nelson DM, Sadovsky Y. Ligand-activated peroxisome proliferator activated receptor gamma alters placental morphology and placental fatty acid uptake in mice. Endocrinology 2007;148(8):3625-34. http://www.ncbi.nlm.nih.gov/pubmed/17463056
- 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.
- Larkin J, Chen B, Shi X-H, Mishima T, Kokame K, Barak Y, Sadovsky Y. NDRG1 deficiency attenuates fetal growth and the intrauterine response to hypoxic injury. Endocrinology2014;155(3):1099-106. http://www.ncbi.nlm.nih.gov/pubmed/24424031
- Xie L, Mouillet JF, Chu T, Parks wt, Sadovsky E, Knofler M, Sadovsky Y. C19MC microRNAs regulate the migration of human trophoblasts. Endocrinology2014;155(12):4975-85. http://www.ncbi.nlm.nih.gov/pubmed/25211593
- Rubens CE*, Sadovsky Y*, Muglia L*, Gravett MG, Lackritz E, Gravett C*. Prevention of preterm birth: Harnessing science to address the global epidemic. Sci Transl Med2014;6(262):262sr5. (*equal contribution) http://www.ncbi.nlm.nih.gov/pubmed/25391484
- Chu T, Mouillet JF, Hood BL, Conrads TP, Sadovsky Y. The assembly of miRNA-mRNA-protein regulatory networks using high-throughput expression data. Bioinformatics, 2015; epub available. http://www.ncbi.nlm.nih.gov/pubmed/25619993
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)