Tiny solutions are being sought for big liver problems by a scientist at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth).
Armed with two grants totaling $3.6 million from the National Institutes of Health (NIH), Cynthia Ju, PhD, professor, vice chair for research of anesthesiology and co-director of the Center for Perioperative Medicine at McGovern Medical School, is studying molecules linked to life-threatening liver injuries.
The idea is to identify molecules that play a major role in the injury process and then develop ways to either enhance their activity or block them. These molecules are sometimes called drug targets or biologics.
One grant is to mitigate the liver injury that occurs during a transplant, and the other is to lessen the damage that happens during an acetaminophen overdose.
In the liver transplantation study, Ju and her collaborator Wasim Dar, MD, PhD, associate professor of surgery at McGovern Medical School, will build on earlier work showing that a white blood cell known as an eosinophil protects the liver during transplantation.
Ju's grant is to further study the role of IL-33/ST2 signaling in eosinophils and how that signaling leads to protection in order to find potential avenues for therapeutic intervention.
The liver is the second most commonly transplanted major organ, after the kidney, reports the United Network of Organ Sharing. In 2017, 8,082 patients received a liver transplant and 13,885 patients in the United States were on the waiting list for a liver transplant.
In the acetaminophen study, Ju and Zhiqiang An, PhD, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School, are trying to address the alarming number of liver failure cases linked to acetaminophen overuse. It is responsible for nearly half of liver failure cases in intensive care units across the country.
"Patients with Tylenol overdose-induced liver failure also have thrombocytopenia, a significant platelet reduction in the blood," Ju said. "Where the platelets went had been a mystery."
Ju studied liver biopsies from liver failure patients due to the overdose of acetaminophen and found an abundance of platelets in the liver. Interestingly, she found that depletion of platelets in the liver markedly reduced acetaminophen-induced liver injury in mice, suggesting that the excess platelets are causing liver damage. The grant will allow Ju to further study Chi3l1 signaling and the underlying mechanism accounting for its role in causing acute liver injury.
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The grants are titled "Role of Eosinophils in Hepatic Ischemia Reperfusion Injury" and the other is "Role of Chitinase-3-like-1 (Chi3l1) in Acetaminophen-Induced Liver Injury." Both are from the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (R01DK122708 and R01DK121330).
Ju and An are both on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. Ju is the Joseph C. Gabel, MD, Endowed Chair in Anesthesiology at McGovern Medical School.