Molly Kile, MS, ScD is an environmental epidemiologist and a Research Associate at Harvard School of Public Health. This application is for a K01 Mentored Career Development Award combines formal education, structured mentorship and training with a detailed research plan that will allow Dr. Kile to become an independent investigator who specializes in perinatal environmental epidemiology capable of investigating epigenetic-environmental interactions associated with prenatal exposure to environmental chemicals. Epidemiological and experimental studies suggest that the intrauterine environment may represent a biologically sensitive window for chemicals that may impair growth and organ development that result in adverse health outcomes later in life. While the mechanisms behind these relationships are unclear, it has been hypothesized that epigenetic dysregulation is involved. Prospective longitudinal birth cohorts in exposed populations are the optimal design to study the effects of in utero chemical exposures and epigenetic- environmental interactions that could lead to life-long phenotypic changes. For this award, Dr. Kile will use data collected from 3 prospective longitudinal birth cohorts that were specifically designed to evaluate the effects of prenatal metal exposure on perinatal and pediatric health outcomes to 1) examine the association between prenatal arsenic exposure, a common environmental pollutant, and fetal growth;2) investigate the interaction between arsenic and DNA methylation of endothelial nitric oxide gene (eNOS) and the insulin-like growth factor gene (Igf2) which are well characterized and involved in fetal growth and development using umbilical cord leukocytes and umbilical vein endothelials cells;and 3) explore the association between Igf2 gene DNA methylation and fetal growth. Dr. Kile is well positioned to carry out the proposed studies because of her prior research experience in molecular environmental epidemiology and the unique resources available through her mentorship team including access to 3 large established prospective longitudinal birth cohorts that will provide the necessary exposure assessment data, genetic material, newborn measurements and covariate data during this award period;access to state-of-the-art molecular biological laboratories;and, advanced coursework in perinatal epidemiology and epigenetics. The proposed human studies will fill important research gaps in our knowledge of arsenic toxicity and its potential to impact human development that can inform clinical and public health interventions. The proposed training and career development will enable Dr. Kile make substantial scientific contributions and develop the knowledge and skills necessary to become an independent investigator and position her to become a leader in the field of perinatal environmental epidemiology. Public Health Relevance: Adverse fetal growth can lead to low birthweight which is associated with increased morbidity and mortality. As such, understanding the factors that contribute to adverse fetal growth is a public health priority. The proposed studies will fill important research gaps in our knowledge of arsenic toxicity and its impact on fetal growth that could inform both clinical and public health interventions in developing and developed countries.
Adverse fetal growth can lead to low birthweight which is associated with increased morbidity and mortality. As such, understanding the factors that contribute to adverse fetal growth is a public health priority. The proposed studies will fill important research gaps in our knowledge of arsenic toxicity and its impact on fetal growth that could inform both clinical and public health interventions in developing and developed countries.
|Kile, Molly L; Rodrigues, Ema G; Mazumdar, Maitreyi et al. (2014) A prospective cohort study of the association between drinking water arsenic exposure and self-reported maternal health symptoms during pregnancy in Bangladesh. Environ Health 13:29|
|Kile, Molly L; Houseman, E Andres; Baccarelli, Andrea A et al. (2014) Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics 9:774-82|
|Grashow, Rachel; Zhang, Jinming; Fang, Shona C et al. (2014) Inverse association between toenail arsenic and body mass index in a population of welders. Environ Res 131:131-3|
|Seow, Wei Jie; Kile, Molly L; Baccarelli, Andrea A et al. (2014) Epigenome-wide DNA methylation changes with development of arsenic-induced skin lesions in Bangladesh: a case-control follow-up study. Environ Mol Mutagen 55:449-56|
|Pan, Wen-Chi; Kile, Molly L; Seow, Wei Jie et al. (2013) Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes. PLoS One 8:e70792|
|Kile, Molly L; Fang, Shona; Baccarelli, Andrea A et al. (2013) A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders. Environ Health 12:47|
|Pan, Wen-Chi; Seow, Wei Jie; Kile, Molly L et al. (2013) Association of low to moderate levels of arsenic exposure with risk of type 2 diabetes in Bangladesh. Am J Epidemiol 178:1563-70|
|Kile, Molly L; Hoffman, Elaine; Rodrigues, Ema G et al. (2011) A pathway-based analysis of urinary arsenic metabolites and skin lesions. Am J Epidemiol 173:778-86|
|Kile, Molly L; Baccarelli, Andrea; Tarantini, Letizia et al. (2010) Correlation of global and gene-specific DNA methylation in maternal-infant pairs. PLoS One 5:e13730|