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MAP-IT method maps protein interactions directly in primary human tissue sections

Weill Cornell and Yonsei researchers describe a photocatalytic labeling method that identifies protein–protein interactions in human tissue without model organisms in the first discovery step.

MAP-IT method maps protein interactions directly in primary human tissue sections
Photo: Otávio Astor Vaz Costa, Wikimedia Commons, CC BY 4.0 · License: CC BY 4.0

A group from the Department of Pharmacology at Weill Cornell Medical College (New York) and from Yonsei University College of Medicine (Seoul) has described MAP-IT, a method for mapping protein–protein interactions (PPIs) directly in sections of primary human tissue. The paper by Sarah C. Faulkner, Charles D. Warren, Noah Yardeny and colleagues was published in Nature Communications on 3 November 2026; the corresponding author is Jacob B. Geri. doi.orgNature Communicationsdoi.orgOpen source ↗ MAP-IT is an optimized photocatalytic, carbene-based proximity labeling method. doi.orgNature Communicationsdoi.orgOpen source ↗

The authors note that PPIs in diseased tissues represent a promising class of potential drug targets. However, such interactions are typically identified in live cells, in lysate and in genetically engineered model organisms, which, according to the authors, limits the translational value of the findings for human disease. doi.orgNature Communicationsdoi.orgOpen source ↗

Interaction mapping in tissue sections

According to the authors, MAP-IT bypasses the need for model organisms in the initial discovery step, because labeling is performed on primary human tissue sections. doi.orgNature Communicationsdoi.orgOpen source ↗ The team used the method to profile PPIs in situ for target proteins located on the cell surface and in the nucleus. doi.orgNature Communicationsdoi.orgOpen source ↗

In colon cancer, the authors identified new interactors of EGFR and validated them orthogonally, that is, with an independent method. doi.orgNature Communicationsdoi.orgOpen source ↗ The article reports this as a demonstration of the approach on human tissue, and the data concern interaction partners of the protein rather than any treatment. doi.orgNature Communicationsdoi.orgOpen source ↗

Light-patterned labeling

The labeling reaction in MAP-IT is powered by light. The authors coupled it with spatially patterned irradiation by visible light, guided by image segmentation, in order to map location-specific protein interactomes. doi.orgNature Communicationsdoi.orgOpen source ↗ In this way, the set of interaction partners can be linked to a defined region of the tissue section instead of being averaged over the whole sample. doi.orgNature Communicationsdoi.orgOpen source ↗

The work involved several research units: the Department of Pharmacology at Weill Cornell Medical College, the Tri-Institutional PhD Program in Chemical Biology in New York, and the departments of Internal Medicine, Surgery (Division of Colorectal Surgery) and Pathology, together with the Yonsei Cancer Center, at Yonsei University College of Medicine in Seoul. doi.orgNature Communicationsdoi.orgOpen source ↗

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