The collaborative research of the Center is fostered through flexible working groups that bring together a number of investigators interested in a specific research theme. At present there are working groups that encompass researchers interested in: 1) the health effects of biomass fuel use; 2) the relationship between epigenetics, environmental/lifestyle exposures and disease risk; 3) the role of environmental exposures in neurological and neurodegenerative diseases; 4) environmental exposures across the life course; and 5) climate and health. There is overlap in research interest and participation in multiple working groups by Center members.
Biomass Combustion Working Group
Though ambient air pollution remains an important concern in much of the world, total population exposures to noxious combustion pollutants are actually dominated by indoor emissions from cook-stoves using solid fuels such as biomass. Exposure to high levels of indoor air pollution is a daily reality for approximately 3 billion users of solid cook-fuels with estimates that indoor smoke from cooking causes about 1.6 million premature deaths/yr. This health burden is borne disproportionately by women and children, who tend to be indoors and near the fire during periods of peak emissions. In addition, use of dung and crop residue for cooking, rather than being returned to the soil, contributes to loss of soil fertility. Fuel wood collection, a time and labor burden borne primarily by women and children, puts stress on already damaged ecosystems and puts women at risk for sexual abuse. Meeting domestic energy and health needs in a manner that addresses these problems is a major challenge for the poor and for sustainable development and one for which interdisciplinary scientific inquiry can help.
The Biomass WG, organized in 2005 and led by Dr. Joe Graziano, consists of investigators in the Depts. of EHS, Epidemiology, Medicine, Pediatrics and Mechanical Engineering, the Earth Institute, the LDEO and the School of International and Public Affairs. Early work was funded by three pilot projects from both the CEHNM and the Earth Institute. These pilots provided the data leading to the funding of a large intervention study to improve birth weight and acute lower respiratory infections in Ghana that takes advantage of collaborations established during the pilot studies with health researchers in the Kintampo district of rural Ghana. The long term goal is to elucidate the underlying biological mechanisms that are responsible for biomass-mediated disease. A current R01, directed by Dr. Pat Kinney will test the effectiveness, in terms of fuel conservation, air toxics exposure reduction and health improvement, of a cook-stove intervention introduced early in pregnancy.
Another output of the Biomass WG is the development of a major multi-institutional collaboration in India. The recently announced National Biomass Cookstove Initiative of MNES in India has created a window of opportunity for a national Newborn Stove Project directed at pregnant women. Such a project has potential for improving pregnancy outcomes. But the appropriate modalities to reach the targeted women, feasibility of distribution, usage levels, acceptability, and health benefits need to be studied to assist the national government in this context. Drs. Darby Jack and Pat Kinney, together with Drs. Kirk Smith and Michael Bates from UC Berkeley and Drs. Rupak Mukhopadhyay and Manoja K Das of the International Clinical Epidemiology Network, are initiating pilot studies that will identify the suitable mode of distributing the improved low emission cookstoves among pregnant rural women; measure the degree of exposure reduction in indoor air pollution with stove use; and determine the feasibility of capturing data related to pregnancy outcomes through existing networks of Auxiliary Nurse and Midwives and Anganwadi Workers and community health workers. The outcomes of this study will provide a knowledge base for the planning of further large-scale studies and developing the national newborn cookstove initiative as an intervention for reducing low birth weight in rural and low SES households in India.
Epigenetics Working Group
DNA methylation is a major area of study in epigenetics which encompasses changes in gene expression without changes in DNA sequence. There is considerable data supporting the role of DNA methylation changes, both gene-specific promoter hypermethylation and genome-wide hypomethylation, in cancer development. But emerging studies suggest that these and other epigenetic alterations are likely to also have major impacts on other diseases. Equally important is emerging data demonstrating that environmental exposures contribute to epigenetic alterations. The Epigenetics WG, led by Dr. Mary Gamble, encompasses researchers whose work ranges from animals studies to epidemiologic studies in humans with cancer, respiratory diseases and neurologic diseases.
Animal studies are looking at the multigenerational effects of environmental exposures on DNA methylation. Studies in cancer investigating gene-specific methylation in tumor tissues are providing important information on associations with environmental exposures and disease prognosis in breast and liver cancer. Illumina arrays are being used to identify genes differentially methylated in tumor compared to adjacent tissues (Drs. Regina Santella, Jing Shen), in white blood cells of those with high vs. low arsenic exposure (Dr. Mary Gamble), cord blood from those with prenatal exposure to PAH (Drs. Ricky Perera, Julie Herbstman) and most recently in white blood cells of young girls from families at high and low risk for breast cancer (Dr. Mary Beth Terry). In one project, the array data provided candidate genes whose methylation might be useful for early diagnosis of liver cancer using tumor DNA released into the plasma. Pilot studies demonstrated elevated levels of plasma DNA methylation years before diagnosis.
Global DNA methylation is also being extensively investigated in studies of arsenic exposure, in cancer case-control studies and in studies on the role of in utero and early life factors (Drs. Ahsan, Gamble, Herbstman, Morabia, Orjuela, Perera, Santella, Shen, Tang, Terry). The mechanisms that drive changes in methylation patterns are not known. Studies of early life factors are using biospecimens from adults whose mothers were followed during pregnancy with information available from questionnaires and in some studies using biospecimens collected during pregnancy. This work has produced important basic information on differences in methylation in different white blood cell types that will be critical for determining which biospecimens should be used for analysis in future studies. Remarkable pilot data have suggested that young girls from families at high risk of breast cancer have lower levels of global DNA methylation than those at lower risk. Expansion of these studies will provide useful information to improve understanding of familial risk. Other studies are examining the effects of diet, lifestyle factors and environmental exposures on methylation.
More recently, Center members have begun studies of histone modification and microRNAs. Dr. Mary Gamble is working with Dr. Max Costa at NYU’s NIEHS Center to analyze histone modification in white blood cell samples from individuals with high vs. low arsenic exposure. Dr. Regina Santella has an R03 to investigate the use of plasma microRNAs as early biomarkers of breast cancer and a Center pilot to Dr. Jing Shen is looking at microRNAs in liver cancer cases and controls.
Environmental Exposures across the Life Course Working Group
It is becoming increasingly clear that the timing of environmental exposures plays a major role in determining the resulting health effects. Accumulating epidemiological evidence points to the long-term influence of prenatal and early postnatal environments on adult health. Birthweight and other measures of infant size have been negatively correlated with a diverse range of adult diseases and positively associated with some adult cancers such as breast cancer. To fully understand these persistent correlations, epidemiological studies need to start in pregnancy, and perhaps even before conception, as birthweight itself is a crude proxy for the intrauterine environment. Postnatal measures are also needed to capture the complex interplay linking the pre- and postnatal environment to adult health. The rates of postnatal growth and early childhood body size have been shown in some studies to be just as or even more important than birthweight in predicting adult health.
Recent interest in characterizing exposures over the life course, and their cumulative effect on health outcomes drove the reorganization of this WG. The current approach of examining one exposure on a single outcome is naïve as individuals are exposed to many environmental substances at different points in their life. Capturing this vast quantity of data, and reducing such data to manageable constructs is a developing and cutting edge science. The overall goal of this WG is to educate Center members on current approaches to these problems and to encourage them to incorporate them into new grant proposals. At present, life course exposures are classified into two paradigms. The first, generally called the exposome, is based on high throughput technological measures of exogenous exposure biomarkers at a single point (or multiple points) in time. The second can be characterized as a more detailed study of exposure mixtures, accounting for both the types and timing of exposures; this is most often performed in longitudinal cohorts. Dr. Factor-Litvak, leader of this WG, and Center members hope to incorporate both paradigm measures into ongoing and future studies.
The working group has made substantial progress in supporting already funded projects and in fostering new collaborations. A TRANSFORM T32 was awarded to predoctoral student Megan Horton to evaluate associations between exposure to mixtures of endocrine disruptors on maternal thyroid hormone level. Existing Center sponsored projects have the potential to assess exposures over the life course using either the exposome or exposure mixture paradigms. For example, Drs. Factor-Litvak, Whyatt, and Horton are conducting a study of endocrine disruptors, thyroid function and child neurodevelopment. This study was originally funded via a Center pilot award and then obtained NIEHS funding to study PBDEs, PCBs and perchlorate. Mothers and children are currently being followed under NIEHS supplemental funding and under Dr. Horton’s K99/R00 award from NIEHS. This award will allow the measurement of prenatal phthalates. Other Center projects which include possibilities for measurement of the exposome or measurement of exposure mixtures at various times include examining exposure mixtures associated with biomass fuel, examining a multitude of exposure mixtures in the Columbia Center for Children’s Environmental Health cohort, examining exposure to both As and Mn mixtures in the Superfund cohort in Bangladesh, and examining exposure to a variety of endocrine disruptors in Dr. Factor-Litvak’s Child Health and Development Studies.
Because of the large public health implications resulting from exposure to mixtures of environmental chemicals, we anticipate that Center members will build such analyses into new proposals. Efforts to educate Center members about the exposome and exposure mixtures will foster incorporation of these technologies into new proposals.
Climate and Health Working Group
One of society’s greatest challenges in coming decades will be to enhance population health in the face of emerging risks related to climate change. Overcoming this challenge will require new science to identify impacts, mechanisms, and policy levers, and a new workforce of well-trained professionals. Work in the Center is directed at fostering innovative, cross-disciplinary, translational scholarship on the human health dimensions of climate change, with the goal of advancing society’s capacity to understand, anticipate, and prevent associated adverse health consequences. The magnitude and type of health impacts due to climate change will depend on improved understanding of the relationship between climatic variables, vulnerability factors, and disease outcomes. Improved public-health strategies such as indoor climate control, optimum air filtration and ventilation, and improved anticipatory public-health messaging will be critical to adaptation.
Led by Dr. Kinney, this is the newest WG and a relatively new research and training area for the Center and for NIEHS. Close linkages with other University units bring world class additional expertise in earth sciences, climate prediction, and climate impacts assessment. Important partners include the Columbia Climate Center at the Earth Institute - with its global reach and ability to link climate resources across the University, the International Research Institute for Climate and Society (IRI) – whose mission is to make climate information actionable at the local level, and the NASA Goddard Institute for Space Studies – one of the leading climate modeling centers in the world. In addition to enriching the teaching program, these links help to leverage research activities in the Center.
Infectious diseases are highly sensitive to climate influences. Dr. Shaman, a new Center investigator, is a leader in assessing climate influences on infectious diseases. He uses mathematical models, as well as laboratory and epidemiological analysis, to study the effects of humidity and weather on the survival, transmission and seasonality of influenza. In addition, through a newly awarded R01, he is funded to incorporate methods used in numerical weather prediction to develop combined data assimilation/model systems for the skillful forecast of influenza. The Center is fostering the development of this WG by strategically funding two pilot projects to date: a) the effects of weather and air pollution on the productivity of farm workers, now an NIEHS-funded R21 (Dr. Neidell) and b) the role of airborne dust and climate in meningococcal meningitis outbreaks in the Sahel (Dr. Trzaska). We plan to expand climate and health research and training, focused in the four core areas: air quality and heat; pollen and allergic airway disease; co-benefits of greenhouse gas mitigation; and modeling of infectious diseases.