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Early-life environmental exposures - from chemical pollutants to psychosocial stressors - shape lifelong health, yet their complexities remain poorly understood. Many environmental risks remain poorly understood and insufficiently regulated, including many chemical contaminants, micro and nano plastics, unhealthy living environments, climate-related stressors, and psychosocial stress. Most research has focused on single exposures in isolation, rarely addressing how they cluster and interact, or how social and neighbourhood contexts shape them. Compounding this complexity further is the fact that environmental exposures are highly variable over time and thus across the vulnerable time windows, requiring repeated measurements to accurately characterize exposure profiles. Exposomics approaches can capture this real-world complexity by integrating comprehensive exposure data with molecular insights and advanced data analytics. This presentation explores the promises of the exposome, with specific focus on applications during early life vulnerable periods of development. It will show how exposomics approaches have been implemented in longitudinal population-based early-life cohort studies, to systematically and comprehensively study environmental influences for a range of child health endpoints. Further, this presentation aims to share updates and insights from exposome networking and cohort harmonization efforts, including from the International Human Exposome Network project that aims to improve global research collaboration and cooperation on the exposome and develop resources and a research roadmap.

Professor Martine Vrijheid

Barcelona Institute for Global Health, Spain

Professor Martine Vrijheid

Barcelona Institute for Global Health, Spain

Professor Martine Vrijheid is Research Professor and Director of the Environment and Health over the Lifecourse Programme at the Barcelona Institute for Global Health (ISGlobal). As environmental epidemiologist, her research is driven by the need to protect vulnerable population groups, in particular children, from the harmful effects of environmental (chemical, physical and social) exposures. She has a demonstrated record of international leadership in child health, environmental pollutants, and spearheaded the study of exposome and multi-omics determinants of child health. She led European HELIX (Human Early Life Exposome) and ATHLETE (Advancing Tools for Human Early Life Exposome Research and Translation) projects, building deep exposome databases across European cohorts. She coordinates IHEN (International Human Exposome Network), establishing a global exposome network, preparing exposome resources, and developing a roadmap for future exposome research. She is active in a range of international expert panels, advisory boards, and teaching and translational activities.

Immune responses are highly variable from one person to another, with this variability determining differential risks for infection outcome, development of autoimmunity, and responses to therapeutic interventions. Therefore, a better understanding of the causes of such differences has huge potential to improve patient management through precision medicine strategies. The Milieu Interieur consortium was established to address this challenge through a definition of the normal boundaries of a healthy immune response, and the characterisation of their genetic and environmental determinants. To do this we implemented standardised tools for monitoring functional immune responses at proteomic and transcriptional levels, which have been applied to a 1,000 healthy donor cohort. We have quantified and compared the relative impacts of factors such as age, sex, host genetics, and environmental factors on variable immune responses. Among environmental factors we identified cigarette smoking as having strong persistent effects on adaptive immunity, though reversible effects on more short lived innate immunity. Ongoing analysis is exploring the underlying gene transcriptional networks, and through untargeted Mass Spectometry we are quantifying the specific chemical xenobionts that contribute to these altered immune responses. We hope that this approach may serve as a model for studying more complex environmental immune interactions to advance our understanding of exposomic effects on immunity.

Dr Darragh Duffy

Pasteur Institute, France

Dr Darragh Duffy

Pasteur Institute, France

Darragh Duffy is a Director of Research at the Institut Pasteur in Paris where he leads the Translational Immunology unit. He is also co-coordinator of the LabEx Milieu Interieur consortium and holds a position at the Centre for Immunology & Infection (C2i), Hong Kong where he leads the Healthy Human Global Project. The overall goal of his research is to better understand the fundamental mechanisms behind inter-individual differences in immune responses and apply these discoveries to relevant clinical questions. His team applies systems immunology approaches to population cohorts to quantify age, sex, genetic and environmental determinants of immune responses. In parallel they apply the same approaches to experimental clinical studies in infection and autoimmunity. They work closely with clinical collaborators with the goal that the research findings will help to develop new patient management strategies.

As part of the MRC Centre of Research Excellence in Exposome Immunology we have collected together a number of publicly available lung cell and tissue atlases. We are using these atlases to help design experiments and to interpret the results from experiments that explore the relationship between environmental exposures and other perturbations, such as genetic or drug effects, in model systems. Recently there have been several single-cell and/or spatial omics AI foundation models proposed which, in principle, should provide effective cellular modelling and perturbation predictions. I will present some preliminary results on the performance of these models in our exposure-modelling scenarios.

Professor Magnus Rattray

University of Manchester, UK

Professor Magnus Rattray

University of Manchester, UK

Magnus Rattray is Professor of Computational and Systems Biology at the University of Manchester. His research concerns the development of computational methods for analysis of high-dimensional biomedical data with a particular focus on machine learning and probabilistic modelling approaches. He leads a data science team in the MRC Centre of Research Excellence in Exposome Immunology, working on methods to integrate and model high-resolution biological data from different exposures. He is a Fellow of the European Laboratory for Learning and Intelligent Systems (ELLIS) on the ELLIS Health Programme and Director of Manchester’s ELLIS Unit.

With its unique combination of scale, depth, duration and accessibility, UK Biobank is enabling tens of thousands of researchers worldwide to perform innovative discovery science. This talk will provide information about UK Biobank and highlight recent enhancements.

UK Biobank is a prospective cohort study of 500,000 people aged 40-69 years when recruited from across the United Kingdom in 2006-10. It integrates large-scale genomic data (including sequencing) and deep phenotyping data (including lifestyle factors, physical measures and multi-modal imaging) with long-term longitudinal health records. The recent addition of large-scale proteomic and metabolomic data has created an even more powerful resource for enabling better understanding of disease biology and discovery of novel drug targets.

In order to accommodate the increasing scale and complexity of the database, UK Biobank has established a cloud-based Research Analysis Platform. It provides secure access to large-scale computing and novel technologies without the problems of transferring, collating, storing, and accessing these large-scale data. The provision of financial credits for early-career researchers and those in less well-resourced settings democratises access to this unique research resource, further enabling advances in discovery science and improvements in human health.

Sir Rory Edwards Collins FMedSci FRS

UK Biobank

Sir Rory Edwards Collins FMedSci FRS

UK Biobank

Rory Collins is an epidemiologist who studies prevention and treatment of chronic diseases. He is the founding Head of Oxford University’s Nuffield Department of Population Health. During the past 40 years, he has conducted large randomised trials which have demonstrated that clot-dissolving and clot-preventing treatments during a heart attack more than halve mortality, and that lowering LDL-cholesterol with statins safely reduces cardiovascular death and disability. He has led UK Biobank since 2005. Involving 500,000 participants, it is the largest deeply-characterized prospective study globally, available for health research. About 20,000 researchers worldwide actively use it, generating ~5000 papers in 2024 alone.

Microbial and parasite exposures drive biological changes with far-reaching consequences for human health, and provide a framework for understanding heterogeneity in vaccine effectiveness and susceptibility to communicable and non-communicable diseases. This is particularly relevant in tropical low-income country settings, where parasite and microbial exposures are intense and heterogeneous. Leveraging rural-urban contrasts in Uganda, we investigate how the infectome (including helminths and microbial exposures) shapes baseline human biology. Across well-characterised cohorts, we apply high-dimensional immune profiling, metabolomics, and transcriptomics with detailed epidemiological data and vaccine response phenotypes. We identify marked rural-urban differences in the exposome (infectome and microbiome) profiles, accompanied by distinct baseline biological states. For example, rural participants, particularly those with Schistosoma mansoni infection, exhibit immune signatures consistent with chronic stimulation and adaptation, including expansion of CD11c⁺T-bet⁺ B cells, PD-1⁺ NK cells, CRTH2hi CD4⁺ T cells, and activated CD8⁺ T cells, alongside reduced cytotoxic NK cell subsets and non-classical monocytes. These patterns are paralleled by shifts in the metabolome and transcriptome. Multi-omics integration indicates coordinated multi-system reprogramming. Importantly, these baseline biological differences associate with heterogeneity in vaccine immunogenicity. Using predictive modelling approaches, we identify immune and metabolic features that distinguish low and high responders, and demonstrate links between infection exposures, baseline biology, and vaccine immunogenicity. Together, our findings support a model in which the microbial and parasite exposome is a key driver of biological heterogeneity, with implications for both chronic inflammatory disease risk and vaccine effectiveness. Understanding these pathways will be critical for designing context-specific interventions to optimise human health globally.

Dr Gyaviira Nkurunungi

MRC/UVRI and LSHTM Uganda Research Unit, Uganda and LSHTM, UK

Dr Gyaviira Nkurunungi

MRC/UVRI and LSHTM Uganda Research Unit, Uganda and LSHTM, UK

Gyaviira Nkurunungi is an Associate Professor at the MRC/UVRI and LSHTM Uganda Research Unit, and the London School of Hygiene & Tropical Medicine (LSHTM). He leads the Immunomodulation and Vaccines (I-Vac) group in Uganda, integrating expertise in immunology, data science, statistics and epidemiology. The I-Vac group focuses on the immunomodulatory effects of environmental exposures on both communicable and non-communicable diseases, and on vaccine immunogenicity and effectiveness, combining cutting-edge wet-lab techniques with computational approaches to identify biological predictors of vaccine response. He previously led the immunology team on an MRC/UKRI-funded programme of Ugandan vaccine trials exploring population differences in vaccine-specific responses and, with Wellcome and EDCTP early-career funding, designed exploratory studies leveraging the resulting sample archive. Gyaviira’s PhD at LSHTM investigated immunological mechanisms underlying helminth–allergy associations in rural and urban Uganda. He is a member of the EMBO Global Investigator Network and the HypoVax Global Knowledge Hub on Tackling Vaccine Hyporesponsiveness (https://hypovax.org).

The global rise in chronic immune-related diseases, particularly those rooted in early-life susceptibility, cannot be explained by genetics alone, underscoring the need for exposome-wide approaches that capture the cumulative and interacting environmental drivers of immune dysfunction across the life course. The developing immune system is highly plastic, and disruptions during critical windows of susceptibility can lead to persistent immune dysregulation.

Here, we present an exposome-informed approach to mechanistic immunology, integrating high-resolution exposure profiling with multi-omics data from the Baltimore Asthma Exposome Pilot Project. Across children with asthma, we link cumulative exposure profiles to coordinated immune perturbations rather than single-exposure effects. These include activation of stress and MAPK signaling pathways, shifts in CD4+ T cell composition, and signatures of immune activation and senescence. Notably, patterns consistent with Th2 skewing, altered follicular helper T cell dynamics, and expansion of regulatory T cell populations suggest exposure-driven reprogramming of adaptive immunity, alongside changes in innate immune signaling and protein adduct formation.

To address the complexity of exposome-scale data, we developed and applied tidyexposomics, enabling robust integration of exposures with immune phenotypes and identification of exposures that perturb central immune and molecular networks. This framework allows the distinction of stable, biologically meaningful signals from correlated exposure noise.

Together, these findings illustrate how cumulative environmental exposures become biologically embedded in immune function, contributing to chronic disease risk. Ongoing efforts such as through the Global Exposome Forum aim to harmonize these approaches, advancing scalable strategies for exposome-informed prevention of environmentally driven immune-related diseases.

Dr Fenna Sille

Johns Hopkins University, USA

Dr Fenna Sille

Johns Hopkins University, USA

Dr Fenna C M Sillé is an Assistant Professor in Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health, Deputy Director of the Center for Alternatives to Animal Testing, and Director of the JHU Exposome Collaborative. Her research examines how the exposome shapes immune function and disease across the life course, focusing on early-life exposures to arsenic and metal mixtures and their roles in vaccine responses, infection, cancer risk, and neurological disorders. She leads the Baltimore Asthma Exposome Pilot study.

She chairs the Developmental Immunotoxicity Working Group, advancing human-relevant new approach methodologies; and co-develops tools such as tidyexposomics advancing exposome intelligence. She led the Exposome Moonshot Forum, contributing to the Global Exposome Forum. Dr Sillé earned her MS in Immunology and Molecular Virology from the University of Groningen and her PhD in Immunology as a Boehringer Ingelheim Fonds Fellow from Utrecht University for research performed at Harvard and the Brigham & Women’s Hospital, followed by postdoctoral work in functional genomics and environmental health at UC Berkeley.

Measuring human exposure to air pollution creates a technical and data analysis challenge. The UK has a relatively extensive outdoor air pollution measurement network (~300 sites), but even this is hampered by the relatively small number of species measured and the differing representativeness of the measurement locations. Over the past five years, three urban ‘supersites’ have been created that augment the network with measurements of a wide range of other species, enabling a greater assessment of human exposure to poor air quality in the urban environment. Such measurements can be complemented with high resolution satellite measurements to provide a greater spatial coverage for targeted pollutants.

However, as we spend 90% of our time indoors, we must consider air quality within the home and workplace that might be different from outdoors both in terms of concentrations and also chemical composition. This creates even more of a challenge as every building is different and it is often inconvenient to deploy the necessary instrumentation in people's homes. Advancements in lower-cost/miniaturised sensor technologies have enabled the development of highly portable instrumentation suitable for the assessment of personal exposure to multiple pollutants. This enables us to draw more reliable associations between exposure and health effects in panels of hundreds of people.

Professor James Lee

York University, UK

Professor James Lee

York University, UK

James Lee is research professor of atmospheric chemistry at the University of York and the National Centre for Atmospheric Science, based in the Wolfson Atmospheric Chemistry Laboratories. Professor Lee has led the development of techniques to make direct measurements of NOx flux from an elevated site above central London (the BT tower), in Beijing and in Delhi and from aircraft flights over central London. These flux measurements have been compared to the emissions estimates, with the estimates typically under predicting the amount of pollutant emitted. This work has helped improve these estimated emissions, which in turn should lead to improved predictions of current and future air quality and help to direct air pollution abatement. Professor Lee has also carried out research into ozone formation pathways in different cities (eg London, Manchester, Beijing, Delhi), in order to assess the key processes that lead to the formation of this secondary pollutant. This knowledge has then been used to assess the effect of future emission reductions on ozone formation, which do not follow each other linearly.

Being part of EXIMIOUS, a European consortium that aims at describing how environmental exposure can impact immune mediated diseases, we have generated a comprehensive and high dimensional collection of data and parameters form healthy individuals and patients with immune disorders linking their immune profiles to their exposomes, including occupational exposures. For this presentation, we investigated two specific disorders; Hypersensitivity pneumonitis (HP) and Systemic Sclerosis (SSc). Hypersensitivity pneumonitis is an interstitial lung disease caused by an immune response triggered by environmental exposures, including bird proteins. While its pathophysiology is not fully understood, the disease can vary in severity and outcome, ranging from full recovery to severe fibrosis that may require a lung transplant. Moreover, factors predicting the disease outcome are scarce. Systemic sclerosis, is an autoimmune disease where a (unknown) trigger initiates a vascular insult, causing inflammation that ultimately leads to severe tissue fibrosis. In addition, several studies have shown the relevance of occupational dust and chemical exposure for the onset of SSc. The exact pathophysiology driving the disease and triggering the fibrosis is still unclear. With EXIMIOUS we investigated a cohort of 91 HP patients, 120 SSc patients and their respective controls and we performed in-depth immune analysis with detection of proteins in the plasma (OLINK technology) and spectral flow cytometry (40 parameters) of patient peripheral blood. With these extensive datasets, we were able to identify disease specific immune signature in relation to occupational exposures. Results and their implications will be presented and discussed during the meeting.

Dr Stephanie Humblet-Baron

LU Leuven, Belgium

Dr Stephanie Humblet-Baron

LU Leuven, Belgium

Stephanie Humblet-Baron MD PhD is a paediatrician who has started her research career joining the laboratory of Prof. Rawlings (University of Washington, Children’s Hospital, Seattle, USA) where she studied immunology focusing on inborn errors of immunity (IEI). From gene therapy to identification of new immunological mechanisms explaining patient phenotype, including the use of pre-clinical mouse models, her work allowed her to move towards human immunology continuing the exploration of IEI with identification of new genes causing diseases in patients. After a postdoc in Adrian Liston lab (KU Leuven, Belgium), she has started her independent group at KU Leuven where she was recently appointed as tenured associate professor in 2025. There, she has set up a high dimensional single cell analysis platform for human immunophenotyping and her group is running several clinical studies investigating the immune landscape using systems immunology with the aim of unravelling underlying immune mechanisms involved in the studied disorders including IEI, autoinflammation, infectious diseases, cancer, CAR T-cell therapy and neurological diseases.