The purpose of this Mentored Research Scientist Development Award is to support the interdisciplinary career development of the candidate, Dr. Adrienne Ettinger, who is trained as an environmental epidemiologist. This award will support the candidate for a period of mentored research and additional training in scientific and laboratory methods relevant to genetic and molecular epidemiology. This will enable her to subsequently develop an independent, interdisciplinary research program with a focus on transgenerational effects of environmental exposures, including the identification of molecular markers for noncancer (reproductive) health outcomes and analysis of complex gene-environment-nutrient interactions. The proposal outlines a Career Development Plan which includes working with established experts in genetic and molecular biology, endocrinology, toxicology, and advanced statistics, and is enhanced not only by the intellectual and laboratory resources described herein, but also by carefully chosen training activities and a career development involving laboratory experience, didactic instruction, seminars, and both formal and informal exchanges with mentors. The research component is aimed at evaluating if specific genes (VDR, CaSR, PTHR1), involved in the regulation of calcium homeostasis, modify the relationships between maternal lead biomarkers and physiologic parameters during pregnancy and, ultimately, influence fetal and early infant exposures and birth outcomes. An exploratory aim will investigate genomic imprinting and gene expression in the maternal-fetal unit using evolutionary theories of "gestational conflict" to develop a conceptual framework for understanding these complex interactions at the molecular level. The proposed research takes advantage of archived data and biologic specimens from three sequentially-enrolled longitudinal birth cohorts, and a newly-funded forth birth cohort, which provides a unique opportunity to address the scientific aims and makes efficient use of existing resources from an established, ongoing, and productive collaboration between researchers in the U.S. and Mexico and addresses research areas pertinent to the NIEHS areas of special interest: "Single Nucleotide Polymorphisms and Disease Susceptibility" and "Epigenetics: Role in Environmentally Induced Diseases/Dysfunction." Relevance: Epidemiologic and experimental evidence suggest that environmental agents are reproductive toxicants, but relatively little is known about the biological mechanisms of effect. The objective of this work is to understand how common genetic variants, involved in calcium regulation, may impact toxicant-induced pregnancy and developmental outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01ES014907-05
Application #
7995975
Study Section
Special Emphasis Panel (ZES1-LKB-A (R5))
Program Officer
Shreffler, Carol K
Project Start
2008-01-15
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2012-11-30
Support Year
5
Fiscal Year
2011
Total Cost
$128,709
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Huang, Siying; Hu, Howard; Sánchez, Brisa N et al. (2016) Childhood Blood Lead Levels and Symptoms of Attention Deficit Hyperactivity Disorder (ADHD): A Cross-Sectional Study of Mexican Children. Environ Health Perspect 124:868-74
Cantoral, Alejandra; Téllez-Rojo, Martha M; Levy, Teresa Shamah et al. (2015) Differential association of lead on length by zinc status in two-year old Mexican children. Environ Health 14:95
Thomas, Shari; Arbuckle, Tye E; Fisher, Mandy et al. (2015) Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study. Environ Res 140:430-9
Abid, Zaynah; Roy, Ananya; Herbstman, Julie B et al. (2014) Urinary polycyclic aromatic hydrocarbon metabolites and attention/deficit hyperactivity disorder, learning disability, and special education in U.S. children aged 6 to 15. J Environ Public Health 2014:628508
Ettinger, Adrienne S; Lamadrid-Figueroa, Héctor; Mercado-García, Adriana et al. (2014) Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican women. Nutr J 13:116
Basu, Niladri; Tutino, Rebecca; Zhang, Zhenzhen et al. (2014) Mercury levels in pregnant women, children, and seafood from Mexico City. Environ Res 135:63-9
Amarasiriwardena, Chitra J; Jayawardene, Innocent; Lupoli, Nicola et al. (2013) Comparison of digestion procedures and methods for quantification of trace lead in breast milk by isotope dilution inductively coupled plasma mass spectrometry. Anal Methods 5:1676-1681
Zhang, Aimin; Hu, Howard; Sánchez, Brisa N et al. (2012) Association between prenatal lead exposure and blood pressure in children. Environ Health Perspect 120:445-50
Kordas, Katarzyna; Ettinger, Adrienne S; Bellinger, David C et al. (2011) A dopamine receptor (DRD2) but not dopamine transporter (DAT1) gene polymorphism is associated with neurocognitive development of Mexican preschool children with lead exposure. J Pediatr 159:638-43
Claus Henn, Birgit; Ettinger, Adrienne S; Schwartz, Joel et al. (2010) Early postnatal blood manganese levels and children's neurodevelopment. Epidemiology 21:433-9

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