Using Team Science to Understand the Exposome and Children’s Health
DERT Success Story
Robert (Bob) O. Wright, M.D.
Pediatrician, medical toxicologist, and environmental epidemiologist Robert O. Wright, M.D., studies how children’s health is affected by the exposome. The exposome encompasses the totality of exposures to chemicals, diet, and social stressors from conception to death, and how such exposures impact human health during various life stages.
Superfund Research and Team Science Pave the Way for Career in Epigenomics
Wright worked with the Harvard University Superfund Research Program (SRP) Center for 20 years, where he progressed from a trainee to overall center director. “The multidisciplinary approach within SRP trained me to think holistically about the impacts of toxic waste, and the importance of integrating social stressors, genetics, nutrition, and mixtures in environmental health research,” Wright said. “No one is exposed to one chemical at a time. Everything in life is a mixture, and if we are going to understand why people develop disease, we have to realize that all the factors around us – the built environment, chemicals, social stressors, and nutrition – interact synergistically.”
Interested in exploring environmental factors and mixtures on a global scale, Wright moved to the Icahn School of Medicine at Mount Sinai, where he founded the Senator Frank R. Lautenberg Environmental Health Science (EHS) Laboratory . As director of the EHS laboratory and the NIEHS-funded Transdisciplinary Center on Health Effects of Early Environmental Exposures (TCEEE), Wright promotes the team science approach. He also advocates the need for investigators in multiple disciplines to perform exposomics research, including experts in molecular biology, genetics, exposure science, biostatistics, analytical chemistry, and environmental modeling.
"No one is exposed to one chemical at a time. Everything in life is a mixture, and if we are going to understand why people develop disease, we have to realize that all the factors around us – the built environment, chemicals, social stressors, and nutrition – interact synergistically."
Bob Wright, M.D.
The team science approach has proven very successful for Wright and his colleagues. They use novel exposure tools and statistical methods to uncover critical windows of susceptibility, or periods of increased vulnerability to chemicals, which often involve prenatal or early childhood exposure to contaminants.
For example, Wright and TCEEE investigators Manish Arora, Ph.D., and Chris Gennings, Ph.D., have demonstrated the utility of tooth biomarkers as an innovative method to reconstruct early-life exposures to different chemicals. This research team, along with biostatistician Brent Coull, Ph.D. from the Harvard T.H. Chan School of Public Health, also used a statistical method called distributed lag-regression modeling to identify critical windows of susceptibility.
New Insights and Opportunities for Exposome Research: The PROGRESS Cohort
Wright is also the principal investigator of the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) birth cohort in Mexico City. Founded in 2006, PROGRESS studies how exposure to metal mixtures, phthalates, and perceived social stress, may relate to children’s health outcomes such as neurodevelopment and obesity.
Wright and his colleagues used data from PROGRESS to show that prenatal exposure to a combination of high levels of maternal stress and mercury weakened mothers’ levels of cortisol, a stress hormone that controls metabolism and homeostasis.
In a more recent study, Wright and colleagues such as Andrea Baccarelli, M.D., Ph.D., from Columbia University, used distributed lag-regression modeling to show that mothers’ exposure to particulate air pollution during the third trimester of pregnancy was associated with lower mitochondrial DNA content in the cord blood of infants. Changes in mitochondrial DNA can serve as a marker of cumulative oxidative damage. These results suggest that exposure to particulate air pollution during a specific window of time in late pregnancy is associated with increased oxidative stress.
“The thing I am most proud of about PROGRESS is that it has been leveraged for seven research and career development awards,” Wright said. “These awards have been the catalyst for building a pipeline of new environmental health science investigators and advancing transdisciplinary research on the exposome. Mentoring these investigators has allowed me to develop a lot of important collaborations, to which I credit the success of not only the PROGRESS cohort, but my research overall.”
Leveraging Transdisciplinary Expertise to Expand Children's Environmental Health Research
Wright and his colleague, Rosalind J. Wright, M.D., recently received grant funding from the NIH Environmental Influences and Child Health Outcomes (ECHO) Program. They will study prenatal and childhood exposures to chemical mixtures and how the timing of these exposures impacts neurodevelopmental outcomes in children. The Mount Sinai ECHO Consortium, also called the ECHO Consortium on Perinatal Programming of Neurodevelopment, is part of a larger longitudinal study in which 50,000 children are being followed across the United States.
“This research is really exciting,” said Wright. “The ECHO Program provides us with the resources needed to obtain a larger sample size, and therefore increased statistical power, to show the complex interactions among environmental, social, and nutritional factors in predicting adverse health outcomes in children. This is what the exposome is, and hopefully, this is just the beginning of big data for environmental health research.”
A separately funded grant through the NIEHS Children’s Health Exposure Analysis Resource will provide the team of investigators with laboratory resources to analyze samples from the national ECHO study. Laboratory methods will be used for targeted analysis of common chemicals (e.g., metals, pesticides, and flame retardants) and for untargeted analysis, or discovery, of new chemicals associated with childhood health and disease.
- Bello GA, Arora M, Austin C, Horton MK, Wright RO, Gennings C. 2017. Extending the distributed lag model framework to handle chemical mixtures. Environ Res 156:253-264. [Abstract]
- Wilson A, Chiu YM, Hsu HL, Wright RO, Wright RJ, Coull BA. 2017. Bayesian distributed lag interaction models to identify perinatal windows of vulnerability in children’s health. Biostatistics; doi:10.1093/biostatistics/kxx002 [Online 27 February 2017]. [Abstract]
- Wright RO. 2017. Environment, susceptibility windows, development, and child health. Curr Opin Pediatr 29(2):211-217. [Abstract]
- Xu J, Hu H, Wright R, Sanchez BN, Schnaas L, Bellinger DC, Park SK, Martinez S, Hernandez-Avila M, Tellez-Rojo MM, Wright RO. 2015. Prenatal lead exposure modifies the impact of maternal self-esteem on children’s inattention behavior. J Pediatr 167(2):435-441. [Abstract]