The Department of Nutrition Sciences and the Nutrition Obesity Research Center (NORC) at the University of Alabama at Birmingham announce the availability of post-doctoral fellowships funded through the UAB Strategically Focused Research Center – Obesity Network (SFRN33570038) awarded to Dr. W. Timothy Garvey by the American Heart Association.
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Objective
The purpose of the Training Program is to offer fellowships that prepare post-doctoral scientists for careers as independent investigators in multi-disciplinary obesity-related research related to intergenerational transmission of obesity and cardiometabolic disease. The multi-disciplinary program project involves the study of humans and animal models and examines physiological, molecular, and epigenetic mechanisms by which the in utero environment (e.g., maternal Gestational Diabetes, Obesity, and Metabolic Syndrome) programs offspring metabolism in ways that persist into adulthood. The goal is to train future leaders in metabolic, obesity, and cardiovascular disease research.
Eligibility
Support provided for trainees
Key program components
Overall program summary
Our central vision is that events in utero resulting from a dysmetabolic obese environment program infant metabolism in a manner that increases risk of obesity and cardiometabolic disease into adulthood and on to the next generation. We hypothesize that specific pathophysiological processes are imprinted in utero and persist to contribute to obesity in children and adults, including: (i) abnormalities in the secretion and hypothalamic action of satiety hormones; (ii) insulin resistance; (iii) defects in lipid oxidation; (iv) reduced rates of energy expenditure; and (v) inflammation both systemically and in adipose tissue. Furthermore, the bases for these mechanistic processes involve epigenetic alterations at specific genomic sites that arise in utero and produce instrumental alterations in gene expression. Three projects within the UAB SFOC will test these hypotheses both individually and in aggregate. The basic project will study 3 models of in utero stress that differentially affect birth weight, and probe the molecular basis for mechanistic processes that augment fat mass. The human studies (projects 2 & 3) will assess the impact of a dysmetabolic obese in utero environment on offspring over the lifecycle from birth into adulthood. Epigenetic alterations associated with obesity and dysmetabolism will be identified in epigenome wide association studies (EWAS) involving mother-child dyads (children aged 4-10 years; mothers who were lean, obese, or dysmetabolic obese with GDM at pregnancy). These CpGs will be studied in in human neonates (cord blood and at 3 months) and in mouse models to determine the extent to which they arise in utero and the molecular basis by which they predispose to obesity. Thus, while each project will provide new and important discoveries standing alone, the projects are also synergistic in terms of our capacity for data interpretation, strength of conclusions, and understanding of mechanisms. Thus, for the first time, the UAB SFOC will undertake a comprehensive multidisciplinary approach, integrating mouse and human studies over the lifespan, to identify the molecular, metabolic, and epigenetic mechanisms by which a dysmetabolic in utero environment participates in the Intergenerational Transmission of Obesity.
Projects in this award
This is a basic science project that involves an intergenerational study in Murine models. Transgenic models, control breeding schemes, and in vitro fertilization andsurgical implantation will allow extensive study of genetic mechanisms which modify theintrauterine experience for both mother and offspring, as well as the ability to separate effectsof mother to offspring from those of offspring to mother, and even to separate mitochondrialfrom nuclear genetic affects using a newly developed mouse model at our university.
This is a clinical project where women will be identified from among those receiving prenatal care in our network. Women will be recruited into one of three groups: normal weight without diabetes, obese without diabetes, and obese with gestational diabetes. Detailed physiologic and behavioral measurements will be taken of mothers prior to delivery, and of mothers and infants for 3 months after delivery. Epigenetic analyses will also be conducted with hypotheses generated from the Population project. The study minimizes reliance on self-report measures and instead uses objective measures of adiposity, health, and behavior, to the greatest extent possible.
This is the population project enrolling mother-child dyads with the index pregnancy characterized by (1) normal weight without diabetes; (2) obese without diabetes; (3) obese with gestational diabetes. Rigorous phenotyping of health, energy expenditure, diet, body composition, and glucose metabolism will be conducted on the mothers and children when children are 4-10 years of age. Epigenetic analyses will identify differences across groups, especially at sites associated with obesity and dysmetabolism. This information will be used to generate hypotheses to be tested in the mother-neonate and mouse model studies.
Project Program Director and PI:
W. Timothy Garvey, M.D.
Professor, Dept of Nutrition Sciences
Training Program Director:
Julie Locher, PhD
Professor Emerita of Medicine and Public Health
Program Manager:
Jelisa Moseley
For more information:
Write to us at: Department of Nutrition Sciences 1720 2nd Avenue South Webb Building 615 Birmingham, AL 35294-3360 |
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Email us at:
jelisam@uab.edu (for administrative questions) |
Application Procedures
Please send the following material to Dr. Wingo, Application Manager, bcwingo@uab.edu.
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