Environmental Exposures - broadly defined as originating from external sources (air, water, diet, infection, radiation, stress, etc.) and internal sources (inflammation, lipid peroxidation, the microbiome, preexisting disease, among others)1 - are important determinants of human health. Although chronic diseases are thought to result from the combination of environmental exposures and human genetics, the environmental determinants are poorly understood in comparison to the genetic factors. For example, epidemiologists are now able to conduct genome wide association studies (GWAS) with relative ease, but they still rely upon self-reported questionnaires to characterize environmental exposures. This disparity in data quality between genetic and environmental risk factors spawned the concept of the exposome representing all environmental (i.e. non-genetic) contributors to disease - from both external and internal sources - received by an individual during life. By measuring individual exposomes, environment wide association studies (EWAS) can be conducted which simultaneously test disease associations with thousands of environmental exposures.

What types of measurements are best suited for characterizing individual exposomes? On one hand, a top-down approach would combine biospecimens, like blood or urine, with new -omics technologies to profile subjects' internal levels of metabolites, metals, macromolecular adducts, serum proteins, and persistent organic compounds. On the other hand, a bottomup approach would exploit advances in sensor and cell-phone technologies to measure multiple personal exposures to external pollutant levels, as well as host of factors as physical activity, diet, and hormone levels among others. The integration of these two approaches promises to enable us to zero in on important environmental factors and to interleaf EWAS with GWAS.

This workshop will take a close look at emerging technologies that can be used to gather individual exposure information based upon external and internal measurements. Presentations and discussions will explore which of the technologies are "ready now" and which are still "emerging" for use in environmental health research. Particular attention will be paid to the relative advantages and disadvantages of external and internal measurements for characterizing individual exposomes and for performing EWAS. Recent proof of- concept studies will be highlighted and bioinformatic tools will be discussed. This synthesis should inform researchers and policy makers about the critical roles that the exposome concept and new technologies can play in understanding the origins of human diseases.

(8:30AM - 5PM)

8:30 AM Opening Remarks - National Institute of Environmental Health Sciences
8:35 AM Welcome and Workshop Objectives - Stephen Rappaport, University of California, Berkeley

Session 1 Background and Context

Session 1 will provide an overview of the importance of exposure measurements at the level of individuals and the relevance of the exposome concept for integrating scientific disciplines and emerging technologies to better understand the environmental contributors to disease.

Session Chair: William Farland, Colorado
State University

8:45 AM Why We Need to Measure Individual Exposomes - Paul Elliot, Imperial College, London
9:30 AM Using -Omics Methods to Characterize Individual Exposomes - Stephen Rappaport, University of California, Berkeley
10:00 AM Using Personal Monitors and Sensors to Characterize Individual Exposures - Michael
Jerrett, University of California, Berkeley
10:30 AM Break

Session 2 Building the Individual Exposome

Session 2 will take a deeper look at specific emerging technologies to characterize the individual exposome. The first half of the session will explore 'omic tools to characterize exposures at the molecular level. The second half of Session 2 will take a look at recent advances in external technologies to monitor personal exposures and responses. Preliminary findings from the application of these tools in human studies will be discussed as well as their relevance to developing individual exposomes.

Session Chairs: Susan Fisher, University of California, San Francisco; David Balshaw, National Institute of Environmental Health Sciences

10:40 AM Metabolomics Integrated Epidemiology - Elaine Holmes, Imperial College, London
11:10 AM Gene-expression Profiles as Signatures of Environmental Exposures - Avi Spira, Boston University
11:40 AM Plasma Proteomics: Lessons from Breast Cancer Research - N. Leigh Anderson,
Plasma Proteome
12:10 PM Lunch on your own
1:30 PM Sensors to Monitor Individual Exposures to Multiple Air Pollutants - Nongjian Tao, Arizona State University
2:00 PM Personal Measurements of Physical Activity - Stephen Intille, Northeastern/MIT
2:30 PM Monitoring Personal Hormonal Responses to Environmental Exposures - Rajeshwari
Sundaram, National Institutes of Health
3:00 PM Break
3:10 - 5:00 PM Session 2 Panel Discussion

Panelists: Gayle DeBord, National Institute for Occupational Safety and Health; Craig Postlewaite, Department of Defense; Session 2 speakers


(8:30AM - NOON)

Session 3 The Individual Exposome: Proof of Concept Studies

The third session will highlight new research that demonstrates the proof-of-concept of developing an individual's exposome. How new bioinformatic approaches can be used to combine and interpret multiple sources of exposome data will be highlighted. The session will also explore approaches to couple individual-level internal and external measures.

Session Chair: Tina Bahadori, American
Chemistry Council

8:30 AM Proof of Concept of EWAS - Chirag Patel, Stanford University
9:00 AM Integrating Metabolomics and Animal Model Studies Identifies Gut Flora as a Participant in
Cardiovascular Disease - Stanley L. Hazen, Cleveland Clinic
9:30 AM Panel Discussion
Panelists: Stephen Edwards, U.S. Environmental Protection Agency; Nathaniel Rothman,
National Cancer Institute; Session 3 speakers
10:30 AM Break

Session 4 Individual Exposomes and
Environmental Health Decisions

The final session will explore the relevance of emerging individual exposome data for environmental health research and regulatory decisions. Discussions will focus on how characterizing the individual exposome may cause a shift from single-chemical exposure assessment to a multiple environmental stressor paradigm that links exposures to health outcomes, and how this shift will impact public policy.

Session Chair: Steven Rappaport, University
of California, Berkeley

10:40 - 11:45 AM Roundtable Discussion
11:45 AM Workshop Summary - Steven Rappaport, University of California, Berkeley
12:00 AM Workshop Adjourns (post-workshop committee and liaison meetings until 3:00pm)