Ming-Hui Zou, M.D.,Ph.D.
Molecular and Translational Medicine
Georgia State University
It’s common wisdom that regular exercise prevents obesity, diabetes and cardiovascular diseases such as high blood pressure. What’s less known is how this works at the cellular level. It’s a complex series of events that Ming-Hui Zou is unraveling – and his research may be opening the door to new treatments for coronary heart diseases and a host of related ailments.
Zou is particularly interested in the role of an enzyme called AMPK, which regulates glucose, fat and cholesterol, influencing energy and metabolism. He discovered that although AMPK is activated in part by oxidants and “free radicals” formed in exercise, it also relies on instructions from a gene known as LKB1.
In a 2014 study, Zou and his lab identified a sequence of DNA that eliminated the LKB1 gene from the endothelial cells lining the blood vessels of mice. The mice that lost the gene developed high blood pressure – without it, no signal was sent to the AMPK enzyme. (And in a separate study of his group, he also found that tumors deficient of the LKB1 gene also grow and spread faster.)
Zou and his team are now searching for a drug compound that would simulate the LKB1 gene’s activation of AMPK. Instead of just treating the symptoms of hypertension, as commonly prescribed drugs do, such a medicine would treat the cause. It might also offer a way to treat diabetes, obesity, coronary heart diseases and cancers.
Zou’s broader area of investigation is “oxidative stress,” a kind of toxicity caused by an excess of reactive oxygen molecules, or volatile compounds sometimes called "free radicals." Reactive oxygen molecules are a natural by-product of cellular processes, so some level is perfectly normal. But when these molecules overwhelm the body's ability to process them, the resulting oxidative stress damages cells and causes disease.
Which is how Zou came to make the connection between the LKB1 gene and the AMPK enzyme. He and his lab were the first to discover that AMPK has a built-in mechanism to detect oxidative stress —— and it responds by suppressing the cell’s production of reactive oxygen molecules.
Zou is internationally recognized for his research on vascular biology and disease. In particular, his research focuses on how the body senses and reduces oxidative stress, or alleviates its harmful effects. His contributions to the field include:
- Discovering the peroxynitrite-prostacyclin synthase-thromboxane receptor pathway in oxidants-induced endothelial dysfunction. Finding that selective modification of prostacyclin synthase is a critical event in numerous diseases including diabetes, hypertension, and coronary heart diseases;
- Characterizing molecular mechanisms of endothelial nitric oxide synthase (eNOS) uncoupling, which is critical in the deregulation of vessel function in diabetes and cardiovascular diseases. These works are important as they explain how diseased vessels trigger heart attack;
- Discovering that AMP-activated kinase (AMPK), which helps regulate energy metabolism, obesity, diabetes, and cardiovascular diseases, functions as a sensor and regulator of oxidative stress; Characterizing signal transduction pathways of LKB1 and AMPK; Defining the molecular mechanisms by which Glucophage, the no. 1 anti-diabetes drug in the world, exerts its therapeutic effects;
- Elucidating the molecular mechanisms of protein ubiquitination and proteasome activation in hypertension, atherosclerosis and diabetes; Identifying protein kinase B (Akt)-protein phosphotase PTEN as targets of oxidants and insulin resistance;
Discovering how cigarette smoking promotes diabetes by promoting body weight loss and abdominal aortic aneurysm, a devastating disease with over 80% mortality.
Dr. Zou research is focused on translating important molecular research findings into therapeutics and treatment options that can help patients. Zou says, "I'm excited about the opportunity to build an outstanding team of scientists. I was drawn here because of GSU's dedication to translational research and creating more jobs for the state of Georgia."