Professor awarded $446K grant to fight ‘complex’ deadly infection, sepsis

Five years ago when Harnett County native Kelly Jones went to visit her older sister in the hospital, she thought Carmen just had a stubborn case of the flu. The sore throat, aches and pains that Carmen’s family had all come down with was subsiding, but Carmen’s symptoms had hung on longer than normal.

She was given antibiotics and sent home to rest. But Carmen didn’t get better. The next visit’s tests revealed she was already in kidney failure.

“As soon as I saw her, I knew something was seriously wrong,” Kelly said. “I asked what tests were done and all they had done was bloodwork. She was breathing fast, her color was not good, [and] her skin was mottled. I demanded that they start looking into what was really going on, because it was more than just the flu.”

Kelly and her mother are both nurse practitioners, and while the ER staff and local doctors never said the word “sepsis,” they both had their suspicions. Hours later the hospital determined that Carmen was in septic shock. Carmen’s organs began shutting down at 8 a.m. on Dec. 18

By 3 a.m. the next day, she had passed away.

“Had it been caught earlier, there would have been a potential for survival,” Kelly says. “I hope they’re doing more to teach staff about what signs to follow.”

Sepsis is the leading cause of death in intensive care units in the United States. Its mortality rate increases 8 percent for every hour that treatment is delayed, and as many as 80 percent of sepsis deaths could be prevented with rapid diagnosis and treatment. It affects more than 26 million people worldwide each year and is the largest killer of children.

Dr. Hong Zhu came to Campbell in June 2013, joining her husband on staff at the new School of Osteopathic Medicine in a small lab that they furnished and equipped themselves. Today, she is the vice chair of the Department of Physiology and Pathophysiology and an associate professor of physiology.

This year, she was awarded a $446,625 grant from the National Institute of General Medical Sciences for research on the development of sepsis — “It is imperative to develop effective therapies for managing this dreaded disorder,” she says.

Zhu started to work in the medical research field 20 years ago and developed an interest in oxidative stress (a disturbance in the balance between the production of reactive oxygen species — or free radicals — and antioxidant defenses) and its involvement in organ failure. More specifically, she wanted to research organ failure when it is a result of toxicity induced by cancer-fighting drugs.

With the grant, Zhu will study the upregulation (when a cell produces more RNA or protein in response to an external stimulus) of internal antioxidative/anti-inflammatory networks by naturally derived compounds in multiple organs and will determine the therapeutic effects of this upregulation and the progression of sepsis in animals.

“Though the pathophysiology of sepsis is not completely understood, it is believed that sepsis is the culmination of complex interactions between the offending pathogens and host immune system,” Zhu says,  “leading to dysregulated inflammation, multiple organ failure and eventually death.”

Zhu and her husband, Dr. Yunbo Li (assistant dean for biomedical research and professor and chair of pharmacology) are exploring the ability of a chemical compound called D3T to regulate antioxidatives, protecting cells from toxicity and, hopefully, treating sepsis.

“A lot of people know that eating broccoli is good, but they don’t know why,” Zhu explains. “When you read literature about the healthy qualities of grapes, blueberries and red wine, you’re probably reading about compounds that can produce antioxidative enzymes. We study those chemicals, extracted and purified, to see how they can help prevent or slow the development of diseases that stem from toxicity.” 

Zhu tests on a variety of animals, which she breeds and cares for personally. For her current research, she uses mice that have been genetically modified to carry a transcriptional factor hooked to a luciferous chemical — the same chemical that makes fireflies light up. Her lab equipment picks up on the light generated when the factor is activated. Then, Zhu can read the interaction in the animals’ system. But using the mice for testing can be tricky and expensive. Zhu easily works with 20 mice on a busy day in the lab, and each new mouse costs $340. Luckily, Zhu can keep up with animal breeding year-round while teaching courses at Campbell.

“I’ve been invested in this research for 10 years now,” Zhu says. “I do teach a lot of lectures, but I try to focus on research from February to September.”

The grant funding period for Zhu’s sepsis research will continue until April 2021.


Kate Stoneburner Writer
Lynsey Trembly Photographer

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