NEXUS Leadership Reflections from the Exposome Moonshot Forum

The inaugural Exposome Moonshot Forum took place in Washington, D.C., from May 12 to 15, bringing together diverse stakeholders from industry, academia, and government to chart the future of the Human Exposome. The Exposome Moonshot Forum employed a broad stakeholder engagement format, comprising panel discussions and breakout sessions. This structure enabled all voices to be heard, ultimately promoting alignment, global efforts, and collaboration throughout the field on its twenty-year anniversary, and moves into a new era. Over the course of three days, participants identified next steps and opportunities necessary to achieve the goals of the exposomics field and establish a global Human Exposome Initiative.

The Exposome Moonshot Forum was hosted at the Johns Hopkins University Bloomberg Center by Fenna Sillé, Ph.D. and Thomas Hartung, M.D., Ph.D., and organized with input from an international Organizing Committee - (see list of committee members)¹. Sillé and Hartung lead a collaborative hub of NEXUS, and all of the hubs of NEXUS were involved in providing assistance to the team at Hopkins.

The Exposome Moonshot Forum took place on the twentieth anniversary of the introduction of the exposome concept in Christopher Wild’s foundational paper. During the meeting’s Opening Ceremony, Christopher Wild, Ph.D., remark’s about the field and its journey were shared, which emphasized the significance of the Exposome Moonshot Forum as a key milestone in advancing the field of exposomics and highlighted progress and the growing momentum in the field of exposomics over the past two decades. Similarly, the “Charge to Participants” presentation by Gary Miller, Ph.D., Columbia University, helped set the stage for the meeting by showing a timeline of key achievements and breakthroughs of the past 20 years in the field of exposomics, along with a mostly blank timeline for the next 20 years. This visual served as a powerful symbol that there is much to be defined to operationalize the field of exposomics at a global level, and provides opportunities for all stakeholders.

What distinguished this meeting from others was the focus on global collaboration and the opportunity to engage with such a broad range of stakeholders, particularly industry partners and policymakers, who provided valuable insights into methods of translating exposomics from concept into utility. During the panel “Moving the Human Exposome Project into the Policy-Maker’s Eye” Jeremy Farrar, Ph.D., Chief Scientist at the World Health Organization, provided a key message that “We must use science to advance equity.” This theme resonated throughout the meeting, underscoring the need for exposomics to advance in a manner that benefits the entire global community.

As evidence of the focus on global representation the meeting gathered key leaders from India, Japan, South Africa, Lebanon, Ghana, as well as a significant number of European countries. The wide range of global participation greatly enriched the discussions throughout the meeting. Leaders from across the globe shared existing human cohort data resources and opportunities to conduct truly globally representative exposomics studies that capture the wide array of risk factors and social and cultural dimensions that determine or shape health and well-being across the world. A key theme raised was the need for greater capacity building, infrastructure networks, and collaboration to advance local scientific leadership and impact.

NEXUS was well-represented at the Exposome Moonshot Forum. Chirag Patel, Ph.D., Harvard University, moderated key panels, including ‘Exposome, Big Data, and Artificial Intelligence’ and led multiple breakout sessions on this topic. The Data and AI panel discussed an ambitious and exciting data-driven roadmap for exposomics. Seven experts described approaches on how stakeholders can convert torrents of molecular, clinical, behavioural, and environmental data of the exposome into insights, depending on the use-case, that emerge from the regulatory to research to the bedside.

Highlights included co-moderator Ashwini Davison, M.D., Amazon Web Services (AWS), leading cloud platforms that fuse clinical records with environmental data streams that bring in patient case data, such as those from cancer cases; Marc Chadeau-Hyam, Ph.D., Imperial College London, on making exposure analytics, such as ExWAS, as integrative as possible with genomics; and Intel’s Prashant Shah, M.S., on federated AI that learns across institutions while private data stay put. Michael Skinnider, M.D., Ph.D., Princeton University, demonstrated AI that uncovers unknown metabolites, John Wambaugh, Ph.D., U.S Environmental Protection Agency, previewed EPA’s ExpoCast predictions for thousands of untested chemicals, Nicole Kleinstreuer, Ph.D., NIH, linked organ-on-chip models to real-world risk assessment, and Venkatesh Murthy, M.D., Ph.D., University of Michigan, reminded us of the work that it takes to turn exposomic signals into bedside biomarkers.

Three priorities discussed included:

1. Interoperability first – adopt common standards so multi-domain data flow into shared AI pipelines.
2. Scalable analytics & benchmarks – define community targets (e.g., variance explained, attributable risk) and build the compute and data to meet them.
3. Mechanistic validation loops – pair high-throughput in silico predictions with targeted in vitro or organotypic tests that regulators can trust.

In follow-up breakout sessions, participants — from journal editors to venture capitalists — mapped short-, mid-, and long-term actions, from rapid cohort harmonization tools to “foundation models” for the exposome. While the debate was lively, there was consensus to form a working group, that a formal approach was needed to turn ambition into concrete specification, e.g. IEEE-style.

NEXUS will lead that charge with its partners, launching interoperability working groups and a cloud-enabled ExWAS Workbench test-bed over the next year to support those in the NIH community. NEXUS invites researchers, clinicians, technologists, and community scientists to help make the exposome as measurable and useful for patients, communities, and populations.

Similarly, Rima Habre, Sc.D., University of Southern California, moderated the panel “Enabling Technologies for Advancing Exposomics” alongside Emilie Calabre, Ph.D., Meersens, panelists were asked to envision a future where anything is possible. Este Geraghty, M.D., shared her vision, informed by her global experience as Chief Medical Officer of ESRI, for how reconstructing place-based histories of the totality of exposures could one day revolutionize healthcare - enabling people everywhere on the planet to live longer, healthier lives. Krystal Pollitt, Ph.D., P.Eng., Yale University, spoke to the immense potential of deciphering the vast chemical space for understanding health impacts through scientific community-led standardization of methods and protocols.

Geetha Senthil, Ph.D., NCATS, described a future where quantum sensors can be paired with more traditional sensors to open up a new world of potential for measuring environmental exposures - from electromagnetic fields, to air pollution and chemicals. And finally, Benjamin Barratt, Ph.D., Imperial College London, spoke to the complexity of human behavior and how with exposomics we can start to place people - in space and time - with real-time sensing of exposure, context and behavior, to advance not only personalized exposure and health science but also citizen driven science.

The leaders of the NEXUS ChemBio Hub, Dr. Pollitt and Thomas Metz, Ph.D., Pacific Northwest National Laboratory, led many working group sessions with key stakeholders in satellite meetings. These discussions detailed aspects of the NEXUS Exposome Harmonized Measurements Initiative and lessons learned from past, similar efforts. Additionally, NEXUS Collaborators Douglas Walker, Ph.D., Emory University, Carmen Marsit, Ph.D., Emory University, Arcot Rajasekar, Ph.D., University of North Carolina Chapel Hill, Sophie Thuault-Restituito, Ph.D., Columbia University, Randolph Singh, Ph.D., Columbia University and Carlos Cardenas-Iniguez, Ph.D., University of Southern California, were also in attendance and greatly added to the discussions throughout the meeting.

Overall, the Exposome Moonshot Forum provided a great opportunity for NEXUS to continue furthering its collaborations and discussions with partners in international exposomic initiatives. This includes the International Human Exposome Network (IHEN), which is led by Roel Vermeulen, Ph.D., Utrecht University, and Martine Vrijheid, Ph.D., ISGlobal, and the EIRENE Research Infrastructure, led by Jana Klánová, Ph.D., Masaryk University. Currently, EIRENE is developing much of the needed infrastructure to perform exposomics in a rigorous and harmonized manner.

The Exposome Moonshot Forum concluded with the signing of the Washington Declaration, which planted the stake in the ground for the global human exposome initiative. The global initiative has been named the Global Exposome Forum and the governance structure is being established. Building on the momentum of the Johns Hopkins-hosted Exposome Moonshot Forum, NEXUS, the designated U.S. Exposome Coordinating Center, will now steer the next phase of work across the NIH. Over the coming months, we will convene national working groups, formalize ties with global partners such as IHEN and EIRENE, and implement a shared governance structure that aligns activities across laboratories and domains.