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The Department of Obstetrics and Gynecology Division of Reproductive Sciences

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Jansson-Powell Lab

The placenta determines life-long health

Our research is focused on exploring the cellular and molecular mechanisms that regulate placental function in normal pregnancy and in pregnancy complications and to investigate the role of the placenta in determining fetal growth and long-term health. We employ physiological, molecular and translational approaches, ranging from functional and molecular studies to interventions in high-risk human pregnancies. Our lab utilizes a wide variety of model systems including primary human trophoblast cells and explants, human placental tissue, mice, rats, and non-human primates. A large body of evidence shows that diseases of major importance to public health, including obesity, diabetes and cardiovascular disease originate in early life. In particular, changes in fetal nutrient availability and growth have been shown to strongly associate with chronic diseases in adult age. Fetal nutrient availability is largely controlled by placental function and we have proposed that placental nutrient sensing, a novel function of the placenta, determines life-long health.
Thomas Jansson    
The 2005 International Federation of Placenta Associations (IFPA) award 'in recognition of outstanding contributions to the field of placentology'
Theresa Powell
Giorgio Pardi Foundation Senior Scientist Award (Society for Gynecologic Investigation, 2010)
Contributions to Science:Day2_Repro_Gyn_staff82GA.JPG
Normal fetal growth and development are dependent on nutrient availability, which is a critical 
function of the placenta Both inadequate and excess fetal nutrition lead to the development of pregnancy complications, such as intrauterine growth restriction (IUGR) and fetal overgrowth. Epidemiological data suggests that pathological fetal growth, and therefore altered placental function, increases the risk of obesity, diabetes, cardiovascular disease and cancer in adult life. This offers unprecedented opportunities to develop novel strategies targeting the placenta to treat complications in pregnancy and to prevent the development of disease in childhood and in adult life.  However the underlying mechanisms remain elusive. Our research program addresses this significant gap in knowledge. In particular, we systematically study placental function in animal models and in the human.


Thomas Jansson, MD/PhD, Professor, Principal Investigator
Theresa Powell, PhD, Professor, Principal Investigator
Frederick Rosario Joseph, PhD, Instructor
Veronique Ferchaud-Roucher, PhD, Visiting Scientist 
Professional Research Assistants:
Anita Kramer, BS, Senior PRA, Lab Manager
Stefan Haugen BS, PRA
Kathryn Erickson MS, PRA
Post-Doctoral Fellows:
Owen Vaughn, PhD
Trond Michelsen, MD
Elena Silva, PhD
Marisa Castillo-Csatrejon, PhD
Laura James-Allan, PhD
Clinical Fellows:
Natalia Grindler, MD
Rebecca Jessel, MD
Stephanie Skuby, MD
Megan Gossling, MD
Amin Ramzam, MD

Below: Lab members Paige Cooper, Rebecca Jessel, Stephanie Chassen, and Megan Gossling on a typical Colorado adventure  at Maroon Bells while attending the Aspen Snowmass Perinatal Symposium in August 2016. Can you spot which wildlife species they are running from?

Placental insufficiency is more than decreased blood flow. 

A lack of normal increase of maternal placental blood flow (sometimes referred to as “placental insufficiency”) constitutes the most common cause of intrauterine growth restriction in Western societies.
We demonstrate
d that IUGR is associated with down-regulation of specific placental nutrient transporters in humans and animal models. This finding directly supported the emerging concept that placental responses to reduced placental blood flow are highly complex and, in fact, contribute directly to reduced fetal growth.
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Discovery of novel regulators of amino acid transporters.

Following our demonstration that IUGR and fetal overgrowth are associated with specific changes in placental nutrient transport activity, we performed a number of studies in animal models and primary human cultured trophoblast to identify factors regulating key placental nutrient transporters. This work led to the discoveries that placental amino acid transporters are regulated by leptin, adiponectin and mTOR signaling. Using siRNA to target specific genes in primary human trophoblast cells, we demonstrated that post translational mechanisms under the influence of mTOR Complex 1 and 2 regulate trophoblast amino acid transporters.

Placental nutrient sensing model.

We have developed a novel model for regulation of placental function highlighting maternal signals that impinge upon the syncytiotrophoblast, the placental epithelium, due to the intimate contact with maternal blood.  Formerly the placenta was thought to be regulated predominantly by the fetus and that the fetus acts as a parasite.  We propose that the placenta integrates a multitude of maternal and fetal nutritional cues through intrinsic nutrient sensing signaling pathways to match fetal growth rates with the maternal ability to supply nutrients.  This complex integration of maternal physiology, placental growth and nutrient transport we have called placental nutrient sensing. This ensures optimal allocation of resources between the mother and the fetus to maximize the propagation of parental genes without jeopardizing maternal health. Thus, placental nutrient sensing modulates maternal-fetal resource allocation to increase the likelihood of reproductive success.  

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mTOR as a novel folate sensor.

We recently discovered that mTOR functions as a folate sensor. Folate deficiency in pregnant mice causes inhibition of mTOR Complex 1 and 2 in maternal tissues and in the placenta, decreased expression and activity of key amino acid transporters in the placental barrier and fetal growth restriction. Folate sensing by mTOR was demonstrated in cultured trophoblast cells and in human cell lines (HEK293 and MCF7). Thus, we identified a novel molecular link between folate availability and cell function and  propose that mTOR folate sensing in trophoblast cells matches placental nutrient transport and fetal growth to maternal folate status. In proliferating cells, including cancer cells, mTOR may modulate cell growth and proliferation in response to changes in folate availability.  

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A novel mouse model of obesity in pregnancy.
We have recently developed a novel mouse model of maternal obesity, which has important similarities with obesity in pregnant women, including up-regulation of placental transport functions and fetal overgrowth. We believe that this model will provide us with new tools to identify the mechanisms linking maternal obesity to poor fetal short and long-term outcomes.

DHA supplementation to improve placental function.

We are investigating potential strategies for therapeutic modulation of placental function in pregnancy that could allow for new treatment modalities.  We are working toward safe, well-tolerated and effective strategies such as improved omega 3 fatty acid status to modulate placental delivery of nutrients to the fetus and improve growth and optimize body composition.  These efforts are inspired by the need to break the vicious cycle between poor intra-uterine growth and life-long health risk. 

Adiponectin as a novel endocrine link between maternal adipose tissue and placental function.

Almost 2/3 of American women today enter pregnancy either overweight or obese and although many of these women have normal pregnancies there is an increased risk to have pregnancy complications such as fetal overgrowth. These children have a higher risk to develop obesity and diabetes. Adiponectin is a hormone that it is produced in adipose tissue and circulating levels of adiponectin are high in lean and low in obese individuals. We have discovered that adiponectin regulates placental function and in contrast to other tissues, adiponectin causes insulin resistance in the placenta.  In lean women with high adiponectin this results in a “physiological brake”  to prevent excess nutrient transfer to the baby. In obese pregnant women with low adiponectin too much nutrient is transferred to the baby, stimulating growth and fat deposition. We have recently reported that adiponectin supplementation prevents the excess placental delivery of nutrients to the fetus in obese mice and the fetus grows normally and has normal levels of sugar in the blood.

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R24OD016724         PI: Jansson, Co-I: Powell                   
          6/1/2014– 5/31/2018
A novel mouse model of obesity in pregnancy
The objective of this project is to thoroughly characterize a new mouse model of obesity in pregnancy associated with fetal overgrowth and its links to the development of metabolic syndrome in the offspring.

R01HD078376        PI: Jansson, Co-I: Powell                   
          7/1/2014– 6/30/2019     
mTOR as a trophoblast folate sensor
The central hypothesis is that mTOR regulates trophoblast folate uptake and functions as a novel folate sensor mediated by the proton-coupled folate transporter (PCFT). 

R01HD068370        PI: Jansson, Co-I: Powell                   
          7/25/2011 – 6/30/2017
Molecular Mechanisms Regulating Placental Nutrient Transporters
We explore the role of mTOR signaling in the regulation of placental amino acid transporters. Specifically we test the hypothesis that both mTOR Complex 1 (mTORC1) and 2 (mTORC2) regulate placental amino acid transporter activity by affecting the plasma membrane trafficking of transporters. We further propose that the molecular mechanisms involved are distinct in that mTORC1 activation phosphorylates the E3 ubiquitin ligase Nedd4-2, which decreases transporter ubiquitination resulting in increased amino acid transporter expression at the cell surface whereas mTORC 2 activation stimulates the actin skeleton mediated by PKCa.

PO1HD021350-A1 (PI Nathanielsz), Sub project 1          PI: Jansson              
          2/1/2014– 1/31/2019
Mechanisms of placental nutrient sensing in the baboon
We will test the hypothesis that inhibition of placental insulin/IGF-I, leptin and mTOR signaling constitute a key molecular link between maternal nutrient restriction, reduced fetal growth by down-regulation of placental nutrient transporters, which limits fetal supply of amino acids and methyl donors.
R03HD078313        Multi-PI: Jansson and Gupta                    
          3/1/2014– 2/28/2017     
IGFBP-1 hyperphosphorylation in IUGR: Role of mTOR and CK2
The central hypothesis in this mechanistic proposal is that inhibition of mTOR signaling and activation of protein kinase CK2 in the fetal liver constitutes a key molecular link between nutrient deprivation and increased IGFBP-1 secretion and phosphorylation in vitro and in IUGR in vivo.

R13HD084096         PI: Jansson                      
          03/16/2015 – 02/28/2020
Placenta Association of the Americas Conference Grant
This award supports an annual one-day conference as a satellite meeting the day before the Annual Scientific Meeting of the Society of Reproductive Investigation (SRI).

UG3OD023248        PI: Dabelea, D, Co-I: Jansson             
          09/01/2016 - 08/31/2018
The early life exposome and childhood health - the Colorado Healthy Start 3 cohort study

    1. Dimasuay KG, Aitken EH, Rosario FJ, Njie M, Glazier JD, Rogerson, SJ, Fowkes FJI, Beeson JG, Powell TL, Jansson, T*, Boeuf P* 2017 Inhibition of placental mTOR signaling provides a link between placental malaria and low birthweight. BMC Medicine: In press. (*Co-senior author) 

    2. Cleaton MA, Dent CL, Howard M, Corish JA, Gutteridge I, Sovio U, Gaccioli F, Takahashi N, Bauer SR, Charnock-Jones DS, Powell TL, Smith GC, Ferguson-Smith AC, Charalambous M. Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction. 2016 Nat Genet. 48:1473-1480. 

    3. Rosario FJ, Powell TL and Jansson T 2017 mTOR folate sensing links folate availability to trophoblast cell function. J Physiol, in press. 

    4. Rosario FJ, Dimasuay KG, Kanai Y, Powell TL, Jansson T. 2016 Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2. Clin Sci (Lond). 130:499-512. 

    5. Rosario FJ, Powell TL and Jansson T 2016 Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC. Sci Rep. 6:31705. 

    6. Rosario F, Powell TL, Jansson T. 2016. Regulation of Trophoblast Amino Acid Transporter Trafficking by mTOR Complex 1 is Mediated by the Ubiquitin Ligase Nedd4-2. Clin Science, 130(7):499-512 

    7.Rosario F, Kanai, Y, Powell TL, Jansson T. 2015. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity, 23(8):1663-70. 

    8. Chen YY, Rosario F, Powell TL, Han VKM, Gupta MB, Jansson T. 2015. Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human. Clin Science 129(12):1131-41. 

    9. Aye ILMH, Rosario F, Powell TL, Jansson T 2015. Adiponectin Supplementation in Pregnant Mice Prevents the Adverse Effects of Maternal Obesity on Placental Function and Fetal Growth. Proc Natl Acad Sci, 112:12858-63. 

    10. Aye ILMH, Lager S, Ramirez VI, Gaccioli F, Dudley DJ Weintraub S, Jansson T, Powell TL, 2014. Increasing maternal body mass index is associated with systemic inflammation in the mother and activation of distinct placental inflammatory pathways. Biol Reprod 90:129-. 

    11. Aye ILMH, Gao, X, Weintraub S, Jansson T, Powell TL, 2014. Adiponectin inhibits insulin function in primary trophoblasts mediated by PPARα mediated ceramide synthesis. Mol Endo 4:512-24.