Project Grant R21AI203358

The National Institute of Allergy and Infectious Diseases awarded the Regents of the University of Michigan $195,000 on August 10, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to sequence exosome-associated DNA released from activated neutrophils.

The research characterizes molecular features of DNA secreted from activated neutrophils during innate immune and inflammatory responses. Recent work has revealed that activated and migrating neutrophils co-release chromatin and exosomes containing the secondary chemoattractant leukotriene B4 through a non-lytic mechanism that challenges conventional understanding of neutrophil extracellular trap formation and cell death. Biogenesis of these exosomes is initiated at the nuclear envelope of activated neutrophils, where the transmembrane protein lamin B receptor enables packaging of chromatin with specific epigenetic marks into multivesicular bodies. The investigator hypothesizes that neutrophils selectively release chromatin with specific epigenetic modifications and DNA sequences to mediate anti-inflammatory signaling and facilitate clearance from inflamed sites. The project pursues two aims: isolate DNA from secreted exosomes and nuclear lipid microdomains and perform long- and short-read sequencing to identify molecular features of secreted DNA; and validate and localize secreted DNA sequences using fluorescence in situ hybridization.

Work is performed at the University of Michigan in Ann Arbor, Michigan. The period of performance runs through July 31, 2028.