Identifying The Epigenetic Fingerprints Of Weapons Of Mass Destruction

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With an unparalleled collection of rare biological samples and expertise in profiling RNA sequences, Duke University physicians and engineers are playing a vital role in a major U.S. Defense Advanced Research Projects Agency (DARPA) initiative to rapidly screen individuals for exposure to materials associated with weapons of mass destruction (WMD).

The $38.8-million project, led by Arizona State University, joins a $27.8 project led by Mt. Sinai as one of two national consortiums funded by DARPA’s new Epigenetic CHaracterization and Observation (ECHO) program.

The end goal of ECHO is to build a field-deployable device that can test small biological samples—such as a drop of blood or nasal swab—for evidence of epigenetic “fingerprints” that reveal a detailed history of that individual’s exposure to dangerous materials or pathogens.

Although an individual’s DNA remains the same over their lifetime, their environment can affect how his or her genes are expressed, and these changes leave a lasting imprint on their epigenome—even long after the triggering event has past.  According to DARPA, technology that could rapidly read these epigenetic signatures could speed up diagnosis and treatment for troops who may have been exposed to threat agents or who may be suffering from infections.

In a project dubbed MEMENTO Mapping Epigenetic Memory of Exposure to Observe Duke has been awarded $6.2 million over the next four years to help make this idea a reality.

DARPA’s new Epigenetic CHaracterization and Observation (ECHO) program aims to build a field-deployable platform technology that quickly reads someone’s epigenome and identifies signatures that indicate whether that person has ever—in his or her lifetime—been exposed to materials that could be associated with weapons of mass destruction (WMD)

Led by co-principal investigators Xiling Shen, the Hawkins Family Associate Professor of Biomedical Engineering at Duke, and Christopher Woods, professor of medicine and global health at Duke and chief of the infectious diseases section at the Durham VA Medical Center, the project draws on a treasure trove of rare biological samples to help researchers across the ECHO program discover specific epigenetic signatures associated with various exposures.Duke Global Health Institute researchers will also collect a number of new sample cohorts for use in the DARPA projects to study how epigenetic markers persist over time. Gayani Tillekeratne, assistant professor of medicine and global health, will collect samples from subjects with confirmed dengue virus infection in southern Sri Lanka, where Dharshan de Silva, director and senior scientist at Genetech Research Institute, will pursue a similar cohort of subjects with Burkholderia pseudomallei, the cause of melioidosis. Woods will work with colleagues from Tulane in Sierra Leone to gather specimens from survivors of the Ebola-like hemorrhagic disease Lassa fever and with UCLA investigators in the Democratic Republic of Congo to gather samples from survivors of Ebola outbreaks, including from the very first in 1976.

The resources also include a 20-year historical library of Methicillin-resistant Staphylococcus aureus (MRSA) samples collected by Duke School of Medicine professor Vance Fowler. Lisa Satterwhite, assistant research professor of civil and environmental engineering at Duke, will provide samples from an ongoing program studying the effects of farmworkers’ exposures to organophosphates, which are used in insecticides and are precursors to nerve agents used in chemical warfare.

“Our clinical team has an overarching responsibility to design studies and provide samples to both DARPA projects,” said Woods. “It’s a novel, exciting program that is looking at epigenetic signatures in both real-time exposures as well as their evolution over time. And while there’s a clear defense angle to the work, there’s also a practical clinical understanding that will be beneficial as well.”

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