Jessica Saben, PhD

Jessica Saben, PhD, is a postdoctoral scholar in the laboratory of Dr. Kelle Moley, in the department of OB/GYN. In general, her research interests are focused on understanding the intricate relationship between metabolism and reproductive function and how dysfunction on either end of this relationship can affect the other. Jessica received her PhD from the University of Colorado Anschutz Medical Campus. Under the training of Dr. Paul MacLean and Dr. James McManaman, she tested the effects of obesity and high-fat feeding on maternal and neonatal metabolism during lactation in mice. Using indirect calorimetry and radioactive tracers, she showed that obese mice traffic excess fat calories to peripheral tissues (liver and adipose), consequently producing milk that is lower in fat, which led to altered offspring metabolism and growth. Following completion of her PhD, Jessica joined the research team at the Arkansas Children’s Nutrition Center as a postdoctoral fellow under the mentorship of Dr. Kartik Shankar. At the center, she continued to research maternal obesity and nutrition, however now with a focus on placental biology and fetal programming. In her first postdoctoral fellowship, Jessica discovered that maternal obesity is associated with placental inflammation that is regulated by early growth response protein 1 (EGR1). Additionally, she showed that placental oxidative stress and lipid accumulation were also associated with maternal obesity, which may interfere with placental nutrient transport to the fetus. While working with Dr. Moley in her second postdoctoral fellowship, Jessica’s research will concentrate on the effects of obesity and metabolic syndrome on implantation.Obesity and metabolic syndrome decreases the odds that a woman undergoing fertility treatment will become pregnant and increases her risk of miscarriage. These findings suggest that metabolic syndrome increases the risk for early pregnancy loss, which can occur if the uterus fails to become receptive to implantation. It is well known that successful implantation requires that the stromal fibroblasts of the uterus to differentiate into specialized secreting cells in a process termed endometrial decidualization. What is unknown, however, is the extent to which metabolic syndrome affects this process and contributes to infertility. The objectives of this study will be to determine the effects of metabolic syndrome on decidualization and to unravel the mechanisms by which these effects occur. Jessica plans to test the central hypothesis that a high-fructose diet, which is known to contribute to metabolic syndrome, leads to impaired decidualization in both mice and humans and that this occurs because of uric acid-induced oxidative stress.

Publications:
1.  Wahlig JL, Bales ES, Jackman MR, Johnson GC, McManaman JL, Maclean PS. Impact of high-fat diet and obesity on energy balance and fuel utilization during the metabolic challenge of lactation. Obesity (Silver Spring). 2012 Jan;20(1):65-75. doi: 10.1038/oby.2011.196. Epub 2011 Jun 30. PubMed PMID: 21720435.

2.  Saben J, Zhong Y, Gomez-Acevedo H, Thakali KM, Borengasser SJ, Andres A, Shankar K. Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity. Am J Physiol Endocrinol Metab. 2013 Jul 1;305(1):E1-14. doi: 10.1152/ajpendo.00076.2013. Epub 2013 Apr 30. PubMed PMID: 23632636.

3.  Saben J, Zhong Y, McKelvey S, Dajani NK, Andres A, Badger TM, Gomez-Acevedo H, Shankar K. A comprehensive analysis of the human placenta transcriptome. Placenta. 2014 Feb;35(2):125-31. doi: 10.1016/j.placenta.2013.11.007. Epub 2013 Dec 1.PubMed [citation] PMID: 24333048

4.  Saben J, Lindsey F, Zhong Y, Thakali K, Badger TM, Andres A, Gomez-Acevedo H, Shankar K. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 2014 Jan 11. doi:pii: S0143-4004(14)00004-6.10.1016/j.placenta.2014.01.003. [Epub ahead of print] PubMed [citation] PMID:24484739

5.  Debosch BJ, Chen Z, Saben JL, Finck BN, Moley KH. Glucose Transporter 8 (GLUT8) mediates fructose-induced de novo lipogenesis and macrosteatosis. J Biol Chem. 2014 Feb 11. [Epub ahead of print]PubMed [citation] PMID: 24519932

6.  Thakali KM, Saben J, Faske JB, Lindsey F, Gomez-Acevedo H, Lowery Jr. CL, Badger TM, Andres A, and Shankar K. Maternal Obesity is Associated with Augmented Immediate-Early Gene Expression and Altered Insulin Sensitivity in Umbilical Cord. Pediatr Res. 2014 May 12. doi: 10.1038/pr.2014.72. [Epub ahead of print] PMID: 24819376

7.  Saben JL, Bales ES, Jackman MR, Orlicky D, MacLean PS, McManaman JL. Maternal obesity reduces milk lipid production in lactating mice by inhibiting acetyl-CoA carboxylase and impairing fatty acid synthesis. PLoS One. 2014 May 21;9(5):e98066. doi:10.1371/journal.pone.0098066. eCollection 2014. PubMed PMID:24849657; PubMed Central PMCID: PMC4029960.

8.  Saben J, Thakali KM, Lindsey FE, Zhong Y, Badger TM, Andres A, Shankar K. Distinct adipogenic differentiation phenotypes of human umbilical cord mesenchymal cells dependent on adipogenic conditions.  Exp Biol Med (Maywood).  2014 Jun 20. pii: 1535370214539225. [Epub ahead of print] PubMed PMID: 24951473.