Sadovsky Research Group

Principal Investigator: Yoel Sadovsky, MD

The Sadovsky lab utilizes molecular and cellular approaches to decipher mechanisms underlying placental development and differentiation. The trophoblast at the feto-maternal interface fulfills critical functions for embryonic development, including gas exchange, supply of nutrients, removal of waste products, endocrine regulation, and immunological defense.

Using cultured primary human placental cells, genetically-altered mice, and placental samples from abnormal human pregnancies, the lab examines 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.

Specific Areas of Research Include:

  1. Placental nutrition.
    The lab focuses on fat trafficking in the feto-placental unit, where the nuclear receptor PPARgamma plays a pivotal role. After unveiling the expression of PPARg in the human placenta and its function in differentiation and attenuation of trophoblast injury, the lab now examines dynamics of lipid droplets and trophoblastic mobilization of fatty acids and neutral lipids. Current studies decipher the impact of hypoxia on fat trafficking and the role of long chain fatty acids in trophoblast lipotoxicity.
  2. The role of microRNAs in placental differentiation.
    We use miRNA microarray, RNAseq, Nanostring and qPCR technologies to define the trophoblastic miRNA landscape, and the set of miRNAs that respond to hypoxia and other placental insults. By combining computationally identified sets of miRNA targets with transcriptomic and proteomic analysis, we examine 3’UTR targets for placental miRNA, which are essential for trophoblast function. These are interrogated in cell lines and in primary human trophoblasts.
  3. Placental injury and adaptation.
    Seeking to understand the fundamental mechanisms that underlie trophoblast injury, our research focuses on villous hypoperfusion and hypoxia, as these are common pathways for stressors that influence the intra-uterine microenvironment. We examine the expression and function of several identified proteins, including NDRG1, connective tissue growth factor, follistatin-related gene, and their role in placental response to injury.

Contact Information

Yoel Sadovsky, MD

Magee-Womens Research Institute
204 Craft Avenue, A608
Pittsburgh, PA 15213
Phone: 412-641-2675
Fax: 412-641-3898
Email

Lab Members

Magdelena Jennings, BSc

Research Assistant
MWRI Lab A630
(412) 641-3873
Email

Avraham Bayer

Interdisciplinary Biomedical Program Graduate Student
MWRI Lab A630
(412) 641-3873
Email

David Kanter, MD

Fellow in Maternal-Fetal Medicine
MWRI Lab A630
(412) 641-3873
Email

Jacob Larkin, MD

Assistant Professor, OBGYN-Reproductive Sciences
MWRI Lab A630
(412) 641-3873
Email

Abhishek Makkar, MD

Fellow in Neonatal Medicine
MWRI Lab A630
(412) 641-3873
Email

Takuya Mishima, MD, PhD

Postdoctoral Research Associate
MWRI Lab A630
(412) 641-3873
Email

Mayumi Morizane, MD

Visiting Research Scholar
MWRI Lab A630
(412) 641-3873
Email

Jean-Francois Mouillet, PhD

Instructor, OBGYN-Reproductive Sciences
MWRI A634
(412) 641-1684
Email

Christina Pisani, MD

Fellow in Maternal-Fetal Medicine
MWRI Lab A630
(412) 641-3873
Email

Lori Rideout

Research Administrator
MWRI A606
(412) 641-2675
Email

Elena Sadovsky

Research Technician
MWRI Lab A630
(412) 641-3873
Email

Xiao-Hua Shi, MD

Research Instructor, OBGYN-Reproductive Sciences
MWRI A634
(412) 641-3872
Email

Huijie Sun, BSc

Research Assistant
MWRI A634
(412) 641-3872
Email

Lab Alumni

Eyal Anteby, MD
Ibrahim Bildirici, MD
Tal Biron-Shental, MD
Vikram Budhraja, MD
Matthew Carlson, MD
Michael Chau, MD
Baosheng Chen, PhD
Khaled Dibbs, MD
Rogier Donker, MD, PhD
Christoph Dorn, MD
Uriel Elchalal, MD
Haeng-Soo Kim, MD
Gustavo Leguizamon, MD
Carol Lennon, MD
Roni Levy, MD
Qinglin Oh, PhD
Soo-Young Oh, MD
Jeffrey Polish, PhD
Eli Rimon, MD
Cheong-Rae Roh, MD
W. Timothy Schaiff, PhD
Ralf Schild, MD
Christina Scifres, MD
Christina Sonnenberg-Hirche, MD
Tracy Tomlinson, MD
Solange Wyatt, MD
Xiaomei Yan, PhD

Selected Publications

  • Ou Q, Mouillet JF, Yan X, Dorn C, Crawford PA, & Sadovsky Y. The DEAD box protein DP103 is a regulator of steroidogenic factor-1. Mol Endocrinol, 15:69-79, 2001.
  • Mariani TJ, Budhraja V, Mecham BH, Gu CC, Watson MA, & Sadovsky Y. A variable fold-change threshold determines significance for expression microarrays. FASEB J, 10.109, 2002. (Epub).
  • 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 Biol, 28:414-23, 2003.
  • Budhraja V, Spitznagel E, Schaiff WT, & Sadovsky Y. Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays. BMC Biol, 1:1, 2003.
  • Mouillet JF, Sonnenberg-Hirche C, Yan X, & Sadovsky Y. p300 regulates the synergy of SF-1 and Egr-1 in activating LHb gene. J Biol Chem, 279:7832-9, 2004.
  • Chen BS, Nelson DM, & Sadovsky Y. NDRG1 modulates the response of term human trophoblasts to hypoxic injury. J Biol Chem, 281:2764-72, 2006.
  • Schaiff WT, Knapp, Jr. FF, Barak Y, Biron-Shental T, Nelson DM, & Sadovsky Y. Ligand-activated PPARg alters placental morphology and placental fatty acid uptake in mice. Endocrinol, 148:3625-34, 2007.
  • Rimon E, Chen BS, Shanks AL, Nelson DM, & Sadovsky Y. Hypoxia in human trophoblasts stimulates the expression and secretion of connective tissue growth factor. Endocrinol,149:2952-8, 2008. PMC2408813
  • Tomlinson TM, Garbow JR, Anderson JR, Engelbach JA, Nelson DM, & Sadovsky Y. Magnetic resonance imaging of hypoxic injury to the murine placenta. Am J Physiol Regul Integr Comp Physiol, 298:R312-9, 2010.
  • Mouillet JF, Chu T, Nelson DM, Mishima T, & Sadovsky Y. miR-205 silences MED1 in hypoxic primary human trophoblasts. FASEB J, 24:2030-9, 2010
  • Scifres CM, Chen B, Nelson DM, Sadovsky Y. Fatty Acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts. J Clinical Endocrinol Metag, 96:E1083-91, 2011.
  • Mouillet JF, Chu T, Sadovsky Y. Expression patterns of placental microRNAs. Birth Defects Res A Clin Mol Teratol 2011;91:737-43.
  •  Oh SY, Chu T, Sadovsky Y. The timing and duration of hypoxia determine gene expression patterns in cultured human trophoblasts. Placenta. 2011;32:1004-9.
  • Mishima T, Miner JH, Morizane M, Stahl A, Sadovsky Y. The expression and function of Fatty Acid transport protein-2 and -4 in the murine placenta. PLoS One 2011;6:e2586.5

Publications on PubMed

View Publications on PubMed

Services & Protocols

TGenerator

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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, and in Schiaff 2000. Download

News

  • Jake Larkin's abstract, "NDRG1 confers sex-specific protection from  intrauterine hypoxic injury", was accepted for oral presentation at the 2012 Annual Meeting of the Society for Maternal Fetal Medicine.