Stopping Sepsis in Its Tracks

Winter 2014

Fraley is unlocking clues to host-pathogen interactions.
Fraley is unlocking clues to host-pathogen interactions.

The threat of developing a fatal infection from a simple cut or minor wound is as antique as the Civil War and as contemporary as the 12-year-old New York boy who died last spring after nicking his arm and scraping his leg while diving for a loose basketball.

The preventable death of young Rory Staunton turned a spotlight on the bacterial blitzkrieg known as sepsis, inspired congressional hearings and new emergency room procedures, and reawakened echoes of an age when twice as many warriors were killed by unknown and unsuspected microbes than by bayonets or cannonballs.

Today, hundreds of thousands of Americans continue to be stricken every year by what Stephanie Fraley, PhD ’12, calls “the hidden public health disaster.”

“Sepsis kills more people in the United States every year than breast cancer, prostate cancer, and AIDS combined,” notes Fraley, a postdoctoral fellow at the Whiting School who earned her PhD in chemical and biomolecular engineering with Denis Wirtz, the Theophilius Haley Smoot Professor and director of Hopkins’Physical Sciences–Oncology Center and associate director of the Institute for NanoBioTechnology (INBT). (During her graduate years, Fraley was named as a Carl E. Heath Fellow, an ARCS Fellow, and a Siebel Scholar.)

Sepsis is an overwhelming immune response caused by infection of the blood. It can result in organ damage and, in the most severe cases, lead to septic shock and death. In the United States, sepsis occurs in 1 to 2 percent of hospitalizations.

“It is a really scary problem,” Fraley says, “and it’s very important that we not only come up with rapid ways to test for it, since every hour that a person is misdiagnosed increases their chances of dying, but also that we find more effective ways to treat it. Right now, we treat the infection by using antibiotics, but if the patient’s immune system has already gone off the rails reacting to the infection, there aren’t many options to get it back on track. And ultimately this is what kills people.”

Fraley recently won a five-year $500,000 Burroughs-Wellcome Fund Career Award at the Scientific Interfaces for her work on the molecular basis of the human-bacterial interface where sepsis arises. The award supports young scientists as they move from postdoctoral work into full-time faculty positions.

To Fraley, each human body is more than a condominium of cells, proteins, acids, and plasmas—it is a far more complex and mutable multiverse that she collectively characterizes as “a context.”

“Essentially, we are all made up of the same parts, but they come together in very different ways,” she says. “Your context is almost a historical progression of the things that you have been exposed to in your life: the
infections you’ve had, the chemicals you’ve been exposed to, the food you’ve eaten.”

Fraley’s research is an effort to probe the human and bacterial small RNAomes for clues to what happens in that host-pathogen interaction. If successful, her work could hold tremendous promise for quick-response treatment and patient safety in emergency rooms, clinics, and hospital wards. It also holds potential for a better understanding of our individual microbial defenses and susceptibilities.

She is working with professors Samuel Yang, in Emergency Medicine at the Johns Hopkins School of Medicine, and Jeff Wang, in Biomedical Engineering. Both Yang and Wang are also affiliated with INBT.

Fraley grew up in the Tennessee city of Chattanooga, a fulcrum of the American Civil War, the last great conflict to be waged before the discovery of germ theory. In battles like the Union assault on Lookout Mountain above Fraley’s hometown, and in both sides’ fetid prison camps, thousands of soldiers perished from wounds and diseases that other men— Fraley would call them “other contexts”— blithely survived.

“Micro-RNAs may be the key to our individual contexts,”she says, and she is working to develop “technology that allows us to broadly profile all of them very sensitively at the single-molecule level as a tool to understand the differences in populations.”