Research Groups- The following Research Groups organize the Center’s seminars and workshops, the annual winter symposium that coincides with our EAB meeting/retreat, and other enrichment activities.
Multiple Exposures/Mixtures Research Group
Leaders: Dr. Mary Wolff, PhD, Professor of Environmental Medicine
Dr Wolff has over 30 years of research experience in the study of multiple chemical exposures, and is chemist/toxicologist with over 250 publications in environmental health. Chemicals are ubiquitous in our environment, yet few studies have addressed the cumulative and life stage specific effects of mixed chemical exposures1,2. Such studies are critically needed because single-chemical exposures do not mirror real-life scenarios. Although we cannot yet assess all chemicals to which we are exposed, the analytical methodologic work on the “exposome” suggests that mixtures research is of broad interest3,4. Barriers to mixtures research include the expense of measuring multiple biomarkers, the complexity of the data analytical approaches needed and the varying and overlapping toxicodynamics and toxicokinetics of chemicals (among many others). Dr Wolff’s expertise in exposure biomarkers and in the study of their health effects gives her extraordinary insight on these issues. Our Center Members are active researchers on chemical mixtures as we have 2 active R01s on mixtures (R01ES026033 PI Arora; R01 ES013744 PI Wright) and Dr Gennings is the co-PI on a European Union Grant on Mixtures (Integrating Epidemiology and Experimental Biology to Improve Risk Assessment of Exposure to Mixtures of Endocrine Disruptive Compounds). She also co-organized an NIEHS workshop on statistical approaches to mixtures, in 2015. Members of this Research Group have developed statistical approaches to mixtures analysis, used untargeted assays to measure mixtures of exposures in blood/urine and even teeth, and developed methods to identify critical windows of susceptibility for mixtures. Despite our early successes, the field of mixtures is still in its infancy, and considerable research is still needed. Some of the pressing issues that this group will explore include technological advances needed to increase the number of exogenous chemicals that can be measured simultaneously in biological matrices, whether interactions among chemicals occur across time (i.e. does exposure at age 1 year interact with exposure at age 3 years), and perhaps most importantly, how do we translate these complex issues into effective prevention/treatment and risk communication strategies).
Sex-Specific Effects and Environmental Health Research Group
Leaders: Dr. Shanna Swan, PhD, Professor of Environmental Medicine
Dr Swan is a leading researcher in the field of endocrine disruption and has studied the role of sex in environmental health for nearly 40 years. She published the first reports of endocrine-disrupting chemicals (EDCs) disrupting anogenital distance, a marker of male feminization and risk factor for reproductive disorders. Emerging evidence indicates that the nervous, endocrine, and immune systems are much more closely interconnected with sex than was previously known, and recognition of the importance of understanding the influence of sex on chemical toxicity is gaining momentum. For example, it is now clear that lead poisoning affects boys more than girls and that women have both less success at quitting smoking and a higher risk for developing tobacco-related diseases. In contrast, mercury exposure does not have a clear pattern of sexual dimorphism in its neurotoxicity, although gender-specific effects are reported. Many sex-specific effects likely have their origins in early life. The development of various biological systems is organized by sex hormones acting on the hypothalamus during critical windows of development. The disruption of such processes by EDCs in an age-, sex-, or anatomic region-specific manner might reprogram sex hormone receptor expression throughout life. Hence, their altered expression may underlie disrupted reproductive physiology and behavior. Sex hormones are not the only mechanism for sex differences. Sex-dependent differences in xenobiotic metabolism have been extensively documented. Iron metabolism, critical to metal processing in the human body, also differs by sex and may underlie differences in internal dose of metals by sex. Several Center members lead prospective cohort studies that are powered to detect sex differences, notably the Growing up Healthy in Harlem study (PI, Wolff), the PROGRESS study (PI, RO Wright), the TIDES Study (PI, Swan), the PEDS cohort (PI, RJ Wright, and A-PED (PI, Reichenberg). Work by Dr RJ Wright in the ACCESS cohort has shown that prenatal air pollution (PM2.5) is associated with poorer attention among boys, while in the same cohort cognitive domains were more impacted among girls. In the same cohort, prenatal PM exposure was associated with higher risk of asthma but only among boys. Much work remains including 1) the role of culture/behavior on the risk of chemical exposure and what role self- identified gender plays in the risk of exposure; 2) Are there long term consequences to sexually dimorphic effects from early life exposures (i.e. adult health) 3) what systems (endocrine, inflammatory, neurologic, immune etc) drive sex specific effects. Our Center is well positioned to study these and other critical questions.
Social Environment-Chemical Interactions Research Group
Leaders: Dr. Rosalind J. Wright
Dr RJ Wright is a social epidemiologist and pulmonologist who published the first reports of social stressors as a cause of asthma. She is also PI of an ECHO consortium of children in which stress-chemical interactions are the main focus (UG3 OD023337) and recently received an R01 to investigate stress and lung function (R01 HL132338). Many disease states, including obesity, asthma, and neurodevelopmental disorders, are known to be induced by and/or exacerbated by psychosocial stress. These same diseases are also common consequences of environmental chemicals, suggesting shared vulnerability or perhaps underlying synergism between stress and chemicals. This group pursues research that advances our understanding of the ways in which stress and chemicals interact biologically to cause disease. Drs Nita Vangeepuram, Carol Horowitz, and Maida Galvez are studying many aspects of the built environment (green space, walking paths etc) as a predictor of child obesity and asthma, from volatile organic compounds in building materials to social factors, such as access to healthy food and other causes of health disparities. Dr. RO Wright conducts research on stress-chemical interaction and neurobehavior (R01 ES013744). Collectively, our research suggests that chemical and nonchemical environmental exposures in early life can disrupt development of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which can alter immune system development, resulting in increased risk for a variety of disorders. Our team published some of the few prospective studies on stress-lead interactions, including work showing that lead disrupts the normal diurnal cortisol secretion pattern. Because interactions are biological phenomena, understanding them may be key to developing future preventive or treatment interventions. For example, this group might pursue studies to determine 1) what components of social environment (stress, community violence, crime, etc) or psychological correlates (anxiety, depression) co-occur with chemical toxicants and act synergistically and 2) whether positive states/traits (coping, social networks, self esteem etc) mitigate chemical toxicity and whether interventions to reduce stress (e.g., cognitive behavioral therapy or family counseling among others) might mitigate chemical toxicity. Social environment can also be considered part of a larger environmental mixture, relating this work to that of the mixtures group, including the use of “mixture”-specific statistical approaches developed by the BBFC. In fact, we now use weighted quantile sum regression (developed by Chris Gennings, BBFC leader) to analyze salivary cortisol rhythms.