Bio: Dr. Fenna Sillé is an Assistant Professor of Environmental Health & Engineering and Deputy Director of the Center for Alternatives to Animal Testing (CAAT) at Johns Hopkins University School of Public Health. Her research focuses on the human exposome, studying how environmental exposures impact immune development and increase risks for respiratory infections and cancer, as well as how mixtures of exposures influence cognition and neurodegeneration. As Director of the JHU Exposome Collaborative, she leads the JHU hub under the NIH-funded NEXUS exposome coordinating center, and the Exposome Moonshot Forum, advancing exposomics research. Within CAAT, she directs the Metabolomics Core and the Developmental Immunotoxicity (DIT) Program. Dr. Sillé earned an MS in immunology and molecular virology from the University of Groningen and a PhD in immunology from Utrecht University, supported by a Boehringer Ingelheim Fonds fellowship for research performed at Harvard University. She completed postdoctoral training at UC Berkeley, focusing on functional genomics in lymphoma/leukemia and epigenetic biomarkers of arsenic exposure and received an NIH Pathway to Independence Award (K99/R00) in 2015, for her research on early-life arsenic exposure and immunity. She has been recognized with multiple awards from the Society of Toxicology and NorCal SOT.

Abstract: The field of developmental immunotoxicity (DIT) testing is at a crossroads. While growing evidence links early-life environmental exposures to immune-related diseases, traditional DIT assessment remains largely reliant on animal models with limited developmental windows and poor human translatability. As immunotoxicology advances, there is a pressing need to move beyond traditional methods by incorporating state-of-the-art developmental immunology with modern, human-relevant testing strategies. Here, I will explore critical knowledge gaps in DIT, identified by the international working group towards Alternatives to In Vivo Developmental Immunotoxicity Testing. I will highlight our current understanding of age-specific immune vulnerabilities and the long-term consequences of early-life toxicant exposure. Advances in high-dimensional immune profiling, single-cell transcriptomics, and spatial mapping have illuminated key developmental milestones that are susceptible to disruption. Simultaneously, new approach methodologies (NAMs)—including stem cell-based assays, organoid models, in silico systems, and high-throughput functional assays—offer scalable, predictive alternatives to traditional models. I will discuss how these advancements challenge existing regulatory frameworks, highlight the need for NAMs qualification and validation, and propose a roadmap for a more predictive, mechanistic, and human-relevant DIT testing paradigm. By bridging basic immunology with applied toxicology, we can redefine risk assessment strategies and better protect vulnerable populations from immunotoxic insults.

Abstract: NEXUS (the Network for Exposomics in the U.S.) is a NIH-funded coordinating center designed to advance the science of exposomics. Our team is focused on operationalizing the exposome by advancing measurement and modeling technologies and applying them to human health outcomes. The NEXUS is striving to embed exposomics throughout the entire biomedical enterprise. A key aspect is the harmonization of exposomics analysis of biological and environmental samples under our ChemBio Analytical Sciences Hub (led by Dr. Thomas Metz-PNNL and Dr. Krystal Pollit-Yale) as well as geospatial-based exposomics under our Geospatial Sciences Hub (led by Rima Habre-USC and Arcot Rajasekar-UNC). We are also building a comprehensive exposomics digital framework to support exposomics under the NEXUS Data Sciences Hub (led by Chirag Patel-Harvard and Marina Sirota-UCSF). Collaborative hubs include JHU, Emory, CUNY, DSU, and Morehouse SM. Our coordination and harmonization efforts will establish the standard for exposomics profiling that integrates digital, biological, and geospatial markers to make exposome-wide association studies (ExWAS) a reality for studies of all human diseases establishing the paradigm for how we study the environment and human disease. Although NEXUS is U.S. based, we are working closely with partners throughout the world to achieve global harmonization for the field.