High blood pressure, or hypertension, is a major problem worldwide, with the latest estimates suggesting that a billion people across the globe may have this condition. Hypertension not only takes an enormous cost on health and wellbeing, but it also exacts an expensive financial toll. Complications from this condition including kidney disease, and its resulting treatments, such as long-term dialysis and kidney transplant, are some of the costliest conditions the American health care system must contend with.
Mingyu Liang, M.B., Ph.D., has devoted his career to gaining a better understanding of hypertension and its complications, with the goal of eventually developing new ways to treat this burdensome condition. At the heart of his research are short snippets of RNA, called microRNA (miRNA). These bits of nucleic acid, which control the production of proteins throughout cells, could hold the key to checking hypertension in vulnerable individuals.
For this novel research, the American Physiological Society (APS; www.the-APS.org) has recognized the importance of Dr. Liang's work by awarding him the Henry Pickering Bowditch Lecture Award. The award is one of the highest offered by the society and is given to scientists younger than 42 years of age whose accomplishments are original and outstanding.
From Mouse to Man
MiRNA was discovered more than 20 years ago, explains Dr. Liang, but its importance for research and therapies for a variety of health conditions has been recognized only recently. Unlike most other types of RNA, miRNA isn't directly involved in the production of proteins. Rather, these tiny pieces of RNA, averaging 22 units long, regulate the expression of protein-coding genes. They do this primarily by interfering with RNA that's used for creating proteins.
Liang, who has studied aspects of hypertension and kidney disease since receiving his M.B. degree from Shanghai Medical University in 1994, became interested in miRNA just over a decade later. At the time, he says, little was known about the role of miRNA in physiology or disease.
Using animal models of salt-sensitive hypertension, the most common variety of hypertension in humans, Liang has made significant headway in identifying miRNAs that play an important role in influencing the course of hypertension and the resulting kidney disease. After identifying miRNAs of interest in these animals, Liang uses this information as a basis for molecular, cellular, and genetic studies. Taking what he learns from these animal and cellular models, his work culminates in studies on human subjects.
"Our lab runs the full spectrum from very basic cell biology to human subjects," Liang says.
A Big Picture View
Like many researchers, Liang has devoted much of his career to studying individual pieces of miRNA or individual genes. In parallel, however, his work has always embraced a systems approach, seeking to grasp how all the components that contribute to hypertension connect to and cause this condition.
"Studying a single gene or single molecule can be very productive," explains Liang, "but then we always wonder how these bits and pieces fit together. Now we have a lot more tools to allow us to look at whole organs and whole bodies at a deeper level than investigators did years ago. For a complex disease like hypertension, a single gene or molecular mechanism isn't going to be enough to explain it. We're going to have to look for the bigger picture."
Consequently, part of Liang's work focuses on studying the interconnected molecular networks involved in hypertension and kidney disease. This topic will be a key part of his Bowditch lecture, entitled, "MicroRNAs and Systems Molecular Medicine."
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