OKLAHOMA CITY — A University of Oklahoma College of Medicine researcher has reached an achievement matched by only a small group of people – he is among only 13 researchers nationwide to be awarded a sixth RO1 grant from the National Institutes of Health. The RO1 grant is the original and historically oldest grant mechanism of the National Institutes of Health.
Zhongjie Sun, M.D., Ph.D., a professor in the Department of Physiology of the OU College of Medicine, explores better methods for treating diabetes and cardiovascular disease through gene therapy, which allows him to target specific cells without causing the side effects that are often prevalent with other treatments. The gene he has focused on is called Klotho, named for the Greek goddess who carried a spindle and was thought to spin the thread of human life.
“Professor Sun richly deserves this important grant for his outstanding research, which has the potential to benefit so many,” said OU President David L. Boren. “The university is very proud to have Dr. Sun on our research team.”
Research administrative leadership at the OU College of Medicine and the OU Health Sciences Center say Sun’s grants and the trajectory of his investigations are exciting and could pave the way to next-generation therapeutics for many different diseases.
“The NIH currently has over 22,000 active RO1 awards, and only 5 percent of researchers funded by the NIH have more than two RO1s,” said Darrin Akins, Ph.D., Associate Dean for Research in the College of Medicine and a professor in the Department of Microbiology and Immunology. “Dr. Sun is among a select group with his currently funded six RO1 awards. He is a nationally and internationally recognized investigator whose research advances are highly relevant to human health and disease. His work is also a key component of the initiative on our campus to enhance translational research studies – that is, to take innovations and results from basic science studies directly to the patient’s bedside as quickly as possible.”
Sun has harnessed the Klotho gene in his laboratory to reveal its importance in regulating diabetes, hypertension, arterial stiffening and the aortic valve. His studies could provide new disease-modulating therapeutics for some of the most common diseases in the United States.
In studies with type 2 diabetes patients, Sun and his laboratory discovered that they have low levels of Klotho, much lower than patients without diabetes. Using a model where he could directly deliver the Klotho gene to the pancreas, he could lower blood sugar, enhance glucose tolerance and improve insulin storage. These findings could have long-reaching outcomes in future drug development studies.
Sun also has examined Klotho in type 1 diabetes, which is primarily caused by the body actually killing its own cells in the pancreas. The delivery of the Klotho gene to the pancreas in a laboratory model of type 1 diabetes again showed a decrease in blood sugar levels, improved glucose tolerance and increased insulin levels. Sun has applied for a patent to use the Klotho gene in treatment of type 1 and type 2 diabetes and hopes to one day move his research into clinical trials.
“We hope to give Klotho to diabetic patients to see if it can achieve the same therapeutic effects,” Sun said. “This is very promising.”
Sun also has discovered that the Klotho gene is involved in the aging-related conditions of arterial stiffening, hypertension and aortic valve fibrosis. As people age, their blood vessels become stiffer and the aortic valve gradually calcifies so that it cannot close tightly, and heart function becomes impaired. The addition of a high-fat diet only makes the damage more devastating. In his research models, Sun discovered a way to address a Klotho gene deficiency, which resulted in a decrease in severity of arterial stiffening, hypertension and aortic valve fibrosis.
“These have been exciting discoveries for us,” Sun said. “Every day we have new findings and new things to do.”
Sun is a valued educator, teaching courses to both graduate and medical students. He also finds time to review grants for the NIH, and he was the president of the Academy of Cardiovascular Research from 2011 to 2013.
“To have six active RO1 grants from the NIH is incredible,” said James Tomasek, Ph.D., Vice President for Research for the OU Health Sciences Center. “Dr. Sun is a quality researcher, who also actively participates in educating the next generation of researchers. We are proud to have him at OU.”
Sun is a respected member of the Department of Physiology as well, serving as vice chair of research.
“We are gratified to have a researcher of Dr. Sun’s caliber in our department and in the OU College of Medicine,” said Jay Ma, M.D., Ph.D., chairman of the Department of Physiology. “His success is a testament to his dedication to research and his desire to find answers that will improve the lives of Oklahomans and patients throughout the world.”