Postdoctoral Scientist Haikun Zhang, PhD is determined to improve the accuracy and speed with which we diagnose sepsis in critical care settings. Sepsis is a life-threatening medical emergency that happens when the body has an extreme, toxic response to an infection. Instead of just fighting the infection, the immune system triggers a chain reaction that damages healthy tissues and organs – and without fast treatment, it can lead to organ failure and death. Zhang, who works jointly in the labs of Division of Surgical Oncology Professor and Center for Precision Medicine Director Dr. Muhammed Murtaza and Division of Acute Care and Regional General Surgery Assistant Professor Dr. Mehreen Kisat, focuses on developing computational methods and identifying novel biomarkers that can detect and monitor diseases like sepsis.
“Sepsis can be hard to diagnose because its symptoms are similar to those we see when our immune system is responding to non-infectious conditions, like cell damage or cell death that occurs from physical injuries, strokes, and heart attacks. Sepsis is also hard to diagnose because the current tests we have are not sensitive enough to accurately detect it and the tests often require a long turnaround time,” said Zhang.
With the support of a new two-year, $246,618 Career Development (K99) Award from the National Institute of General Medical Sciences, Zhang will be working under the mentorship of Drs. Murtaza and Kisat as well as Department of Biostatistics and Medical Informatics Associate Professor Dr. Zheng-Zheng Tang to begin development of a novel approach for improving sepsis diagnosis. NIH K99 awards are designed to help postdoctoral researchers transition into independent, tenure-track faculty positions and begin with a two-year, mentored phase. After securing a faculty position, Zhang will apply to transition the grant into an independent (R00) award that supports the next 3 years of her research.
For the K99 phase of her award, Zhang will focus on developing computational methods to improve the accuracy of microbial cell-free DNA (cfDNA) detection in blood. Microbial cfDNA refers to small fragments of DNA that are released by microbes into the bloodstream, serving as a biomarker for an infection that could cause sepsis. When she transitions into the R00 phase, she will then work on identifying differences in the fragmentation patterns of host cfDNA – which are small fragments of DNA that our own cells release into the bloodstream – by comparing these patterns in patients with sepsis versus those who are critically ill but do not have an infection. Zhang believes that developing a test that simultaneously analyzes both microbial and host cfDNA could ultimately help improve sepsis diagnosis.
“Microbial cfDNA represents only a small fraction of the cfDNA fragments that can be found in the bloodstream, and these low-level signals can be difficult to distinguish from background noise. We need to find a way to enrich it and distinguish true signals from both background contamination and the cfDNA that comes from harmless or naturally-occurring microbes in the body. Additionally, because host cfDNA is recognized as ‘self’, we may be able to use it to differentiate the immune response that is caused by infection from one that is caused by physical trauma or medical events like strokes,” explained Zhang. “Combined into a single test, microbial cfDNA and host cfDNA could be the one-two punch that helps us identify sepsis quickly and accurately so treatment can begin without delay.”