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NIH grant 1DP2ES039817-01: Mapping Molecular Exposomics: From Blood Biomarkers to Tissue Architecture
Institute: {'code': 'ES', 'abbreviation': 'NIEHS', 'name': 'National Institute of Environmental Health Sciences', 'admin_org_id': '12500022', 'admin_funding_url': ''}. PI: Peng Gao. Award: $722000.
Start: 2026-08-26T00:00:00.
Project Summary
Environmental factors contribute to 70-90% of chronic disease burden, yet we lack fundamental tools to
comprehensively track how chemicals move from blood to tissues and alter cellular function. Current
environmental health approaches capture less than 10% of human chemical exposures, examine tissues as
homogeneous units rather than complex spatial structures, and study molecular responses in isolation. These
limitations prevent understanding which chemical exposures matter most for health, how they accumulate in
tissue microenvironments, and what molecular cascades trigger disease. This project proposes to develop an
integrated molecular exposomics platform consisting of three synergistic modules that provide systems-level
understanding of environmental health across biological scales. Module 1 establishes comprehensive blood
exposomics using high-resolution mass spectrometry-based untargeted analysis to create an unprecedented
catalog of human chemical exposures, routinely detecting over 10,000 chemical features per individual - a
thousand-fold increase over conventional methods. Module 2 employs Desorption Electrospray Ionization
Mass Spectrometry Imaging to visualize environmental chemical distributions in human tissues, revealing the
hidden geography of exposure within organ architecture. Module 3 integrates blood and tissue exposomics
through methodologically consistent electrospray ionization-based platforms, establishing quantitative
relationships linking systemic exposures to tissue-specific accumulation patterns driving localized pathology.
Preliminary studies demonstrate transformative potential. We identified hundreds of environmental chemicals
differentially abundant in pre-diagnostic samples from individuals who later developed lung cancer, including
novel contaminants absent from current biomonitoring panels. Spatial tissue imaging revealed striking
chemical heterogeneity, with certain carcinogens showing ten-fold higher accumulation in tumor regions
compared to adjacent normal tissue, concentrating at sites of early neoplastic transformation. Integration
revealed tissue-to-blood concentration ratios varying over hundreds-fold across chemicals, with many toxicants
undetectable in blood yet accumulating to concerning levels in specific microenvironments. This platform
represents a paradigm shift in environmental health research, challenging fundamental assumptions about
exposure assessment and creating new frameworks for understanding exposure-disease relationships. The
methodologies are universally applicable across tissue types and diseases, from neurodegenerative disorders
to metabolic conditions. Success will fundamentally transform our ability to prevent environmentally driven
diseases through precision interventions based on individual exposure profiles and molecular susceptibilities.
The ambitious scope of attempting comprehensive detection of thousands of chemicals, achieving cellular-
resolution spatial mapping, and establishing quantitative blood-tissue relationships requires the New Innovator
Award's support for high-risk, high-reward research to address biomedicine's most pressing challenges.document fetched 2026-09-06 02:47