12700 East 19th Avenue
Research Complex 2, Room 5121
Aurora, CO 80045
Work Phone: 303-724-3796
Lab Page: https://www.shankarlab.org/
The Shankar Maternal-Child Nutrition Lab conducts research leading to fundamental understanding of the role of maternal and early nutrition in development of obesity, metabolic disease and associated co-morbidities. The laboratory leverages a wide range of experimental approaches including animal models, clinical studies, cell and molecular techniques, and physiological approaches. We widely utilize high-dimensional “-omics” methods to comprehensively understand biological mechanisms of developmental programming.
We collaborate extensively with multidisciplinary groups to understand offspring physiology and placental biology. Our work has begun to elucidate the nature and mechanisms by which maternal obesity and diet impact the offspring, including new insights regarding epigenetic and microbiome changes that can occur in offspring in response to maternal obesity, diet and physical activity.
Maternal Obesity & The Offspring
As the prevalence of obesity increases, so does the incidence of maternal overweight during pregnancy. A major area of investigation in our lab is to understand the developmental origins of childhood and adult obesity, specifically the long-term consequences of maternal obesity. Using genetic manipulations in mouse models of maternal obesity, an important goal is to examine the roles of specific obesity-associated changes (inflammation in utero; maternal and offspring gut microbiome; nutrient transport; and lipotoxicity in the placenta) as causative mechanisms leading to epigenetic changes. The overall objective of these studies is to gain a better mechanistic understanding of the physiological basis of fetal programming.
Sex differences in Development and Developmental Programming
Sex underlies ubiquitous differences observed in many aspects of physiology, development and disease susceptibility, with far-reaching public health consequences. In the context of developmental programming, sexually dimorphic differences have been frequently observed in offspring following maternal dietary and nutritional exposures in both human and animal studies. Despite the ubiquitous evidence, underlying mechanisms contributing to sex differences in offspring remain sparse. We are using genetic and systems biology tools to examine the extent and underlying pathways contributing to sex differences in the placenta and developing offspring.
Obesity & The Placenta
The proper development of the placenta is critical to the health of the baby. The placenta also may be central in determining the long-term health of the baby. We are currently studying the effects of maternal obesity on the development and function of the placenta in animal models and in samples from human subjects at the end of pregnancy. This provides a unique “window” into the intrauterine environment, and molecular changes in the placenta may report on similar changes that occur in the tissues of the offspring.
Epigenetic Mechanisms of Placental Development
The development of the hemochorial type of placenta (found in humans and rodents) critically depends on the formation of the syncytiotrophoblast (STB), which serves as the definitive materno-fetal barrier. Formation and constant renewal of the syncytium occurs via cell-syncytial fusion of the underlying mononuclear cytotrophoblasts (CTB). Hence, the process of syncytialization is critical to the integrity of the STB and in maintaining the essential functions of the placenta. Using a combination of genome-scale methods (RNA-seq, ChIP-seq) and systems biology tools, in conjunction with genetic loss-of-function approaches, we are characterizing novel epigenetic processes required for syncytial fusion.
Bill and Melinda Gates Foundation Krebs (PI) 10/31/2021 – 3/31/2022
“Analyses of biomarkers of EED in Women First data”.
United States Department of Agriculture Ferruzi (PI) 7/1/201 – 6/30/2022
Developmental programming associated with maternal diet and obesity.
Role: PI (Sub-award from Arkansas Children’s Research Institute).
1R01ES032176-01A1 Pearson K (PI) 08/01/2021 – 07/31/2024
National Institutes of Health. Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER) (NIEHS).“Growth and Metabolic Programming from Prenatal PFAS Exposure: Examining the Roles of Placental Functional Genomics and Protection by Maternal Exercise”.
1R01HD102726-01A1 Barbour/Hernandez (PI) 07/2020 - 07/2025
National Institutes of Health (NIDDK). “Triglycerides as a Predictor of Newborn Subcutaneous and Liver Fat: Contributors to Fetal Fat Accretion in Obese Pregnancies”.
3P30DK048520-26S1 MacLean, PS (PI) 08/01/2020 – 07/31/2025
P30 “Colorado Nutrition Obesity Research Center”. The goal of the NORC is to create an environment in which researchers are able to work together to conduct high-quality research in nutrition and obesity.
5R01 DK121497 Thyfault J (PI) 04/01/2019 – 03/30/2024
National Institutes of Health. “Aerobic Fitness, Mitochondrial Dysfunction, and Fatty Liver Disease”, This collaboration with Dr. Thyfault evaluates the role of histone acetylation and associated epigenomic changes in determining differences in intrinsic aerobic capacity in a rat model of metabolic disease.
2T32DK007658-31 Krebs (PI) 10/31/2021 – 3/31/2022
Institutional Training Grant in Pediatric Nutrition. This is a competitive renewal (years 30 – 35) of a training grant focused on pediatric nutrition training.
Role: Co-I / Mentor
1 R21 HD086194-01 Role: PI Shankar (PI) 08/2017 - 07/2019
National Institute of Child Health and Development. “Epigenetic Mechanisms Underlying Trophoblast Syncytialization”. Goals: These studies examined the broad epigenetic alterations associated with syncytialization trophoblasts and examined the role of specific histone acetyltransferases in this process.
ARS Project # 6026-51000-010-NEW-S2 Shankar (PI) 07/2019 - 03/2024
United States Department of Agriculture. “Developmental Programming Associated with Maternal Diet and Obesity”. GoalS: This project focused on understanding the mechanisms of developmental programming in the cardiovascular, adipose tissue and placenta using a mouse-model of maternal HFD. (Relinquished role due to moving institutions).
1 R01 DK084225 Role: PI Shankar (PI) 07/2009 - 05/2014
National Institute of Diabetes and Digestive and Kidney Diseases, “Maternal Overweight: Consequences for Insulin Signaling in Offspring”, This project investigates the influence of maternal obesity on insulin signaling in rat offspring. Using labeled tracers, these studies are investigating if maternal obesity redirects nutrient flux to adipose tissue rather than skeletal muscle, thus favoring adipose accretion.
ARS Project CRIS # 6251-51000-005-02S-3A Shankar (PI) 07/2009 - 05/2014
United States Department of Agriculture., “Prevention of Obesity in the Offspring of Obese Mothers”. This project is aimed at addressing if maternal obesity leads to intergenerational-transmission of obesity to the F2 and F3 generations. Studies in this project are also examining the effect of gestational obesity in a rat model on placental and embryonic development.
5 R01 AT010247 Role: Co-I Pon Velayuthan (PI) 08/2018 - 07/2021
National Institutes of Health / University of Utah. “Biological Signatures of blueberry derived microbial metabolites”, Goals: This collaboration with Dr. Pon Velayuathan was to understand alterations in gut microbial composition and metabolism following blueberry consumption. (Relinquished due to moving institutions)
5 P20 GM109096 Role: Co-I Weber (PI) 01/2017 – 12/2021
National Center for Advancing Translational Sciences. COBRE Center for Childhood Obesity Prevention
Goals: The goals of the CCOP are to build a critical mass of obesity-oriented research focused on multiple domains of childhood obesity. (Relinquished role due to moving institutions)
ARS Project # 6026-51000-010-00-D Shankar (PI) 03/2015 – 06/2019
United States Department of Agriculture. Interventions to mitigate maternal obesity-associated programming
Goal: This translational project examined the efficacy of life-style and dietary interventions in mitigating the detrimental effects of maternal obesity in the offspring.
ARS Project # 6026-51000-010-00-D Role: Co-I Andres (PI) 03/2015 – 06/2019
United States Department of Agriculture. Maternal Programming of Offspring Metabolism and Obesity
Goals: This project examined specific mechanisms contributing to placental inflammation due to maternal obesity using transcriptomic and epigenomic approaches.