The candidate seeks career development support that will build on her interdisciplinary training in toxicology and environmental epidemiology and enable her to advance her scientific career by investigating the possible contribution of DDT exposure in early life to risk of the metabolic syndrome and diabetes. The scientific goal is to test the hypothesis that perinatal exposure to DDT increases risk of metabolic syndrome in aging adults in a dose-dependent manner. The candidate proposes an integrated series of toxicologic and epidemiologic studies. The toxicologic studies (K99 MENTORED PHASE) will incorporate dynamic in vivo physiologic techniques such as metabolic tracers and euglycemic clamping developed in medical endocrinology to explore tissue specific mechanisms of perinatal DDT toxicity in mice. The independent (R00 PHASE) will involve follow-up of the now middle-aged daughters of women who participated in the Child Health and Development Studies birth cohort study in California over 40 years ago and will involve inter-generational life course analyses. The independent phase will conclude with research seeking to identify biomarkers of DDT metabolic toxicity in mice. Metabolic syndrome, often associated with obesity and diabetes, affects over 47 million US residents. Prevalence has increased rapidly in the past decade. The possibility of a toxic environmental chemical contribution to this upward trend is relatively unexplored. There are however, human and mechanistic laboratory data suggesting that organochlorine pesticides, DDT among them, are associated with increased risk of diabetes and the metabolic syndrome. DDT was used extensively in the US until 1972 and is still much used worldwide in malaria control. At the conclusion of training, the candidate will transition to an independent career focused on elucidation of the mechanisms of perinatal exposures involved in metabolic and endocrine dysfunction. These studies should lead to a better understanding of the possible role of environmental toxicants in the etiology of metabolic syndrome and diabetes and will establish a strongly interdisciplinary foundation for the candidate's future research.
This research training program examines the influence of exposure to the insecticide DDT during early development on the rise of obesity, diabetes, high cholesterol and high blood pressure. High body burdens of DDT are found among adults born before its ban in the US in 1972 and in persons of all ages who have lived in regions where DDT continues to be used extensively for malaria control. The ultimate goal of this work is to understand the possible contribution of DDT to metabolic syndrome and to use this information to design strategies for the prevention of metabolic syndrome.
|Mendrick, Donna L; Diehl, Anna Mae; Topor, Lisa S et al. (2018) Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic. Toxicol Sci 162:36-42|
|La Merrill, M A; Lind, P M; Salihovic, S et al. (2018) The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity. Environ Res 160:541-546|
|Cano-Sancho, German; Salmon, Andrew G; La Merrill, Michele A (2017) Association between Exposure to p,p'-DDT and Its Metabolite p,p'-DDE with Obesity: Integrated Systematic Review and Meta-Analysis. Environ Health Perspect 125:096002|
|La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic et al. (2016) Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice. Environ Health Perspect 124:1722-1727|
|Ishikawa, Tomoko; Graham, James L; Stanhope, Kimber L et al. (2015) Effect of DDT exposure on lipids and energy balance in obese Sprague-Dawley rats before and after weight loss. Toxicol Rep 2:990-995|
|Cohn, Barbara A; La Merrill, Michele; Krigbaum, Nickilou Y et al. (2015) DDT Exposure in Utero and Breast Cancer. J Clin Endocrinol Metab 100:2865-72|
|La Merrill, M A; Cirillo, P M; Krigbaum, N Y et al. (2015) The impact of prenatal parental tobacco smoking on risk of diabetes mellitus in middle-aged women. J Dev Orig Health Dis 6:242-9|
|Cohn, Barbara A; La Merrill, Michele; Krigbaum, Nickilou Y et al. (2015) Response to the Letter by Stoop, P. J Clin Endocrinol Metab 100:L123-4|
|La Merrill, Michele; Karey, Emma; Moshier, Erin et al. (2014) Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring. PLoS One 9:e103337|
|La Merrill, Michele; Emond, Claude; Kim, Min Ji et al. (2013) Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect 121:162-9|
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