Yuichiro Suzuki’s Lone Little Lab – the Only One Studying Cardiac Function at GUMC – Is Uncovering the Roots of an Incurable Heart Disorder

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The mysteries of the heart are many, but Yuichiro Suzuki, PhD, has zeroed in on one enigma that has long fascinated him: while the organ is made up of two pumps and four heart chambers of different sizes and with varied roles to play, the cellular biology on the left and right sides of the heart are the same.

Yet the diseases that affect each side are different, and since most occur on the left side, heart drugs are designed to work on that side. And drugs that work on the left side don’t work on the right – even though the cells look and act the same on both sides.

So Suzuki, a professor of pharmacology who specializes in the study of cardiac and smooth muscle biology, decided to investigate how the right ventricle, which pumps deoxygenated blood into the lungs, and the left ventricle, which pumps oxygenated blood to the body, differ at the level of gene and protein functioning.

“We know that the ventricles develop from different master progenitor cells, yet the cardiac muscle that is produced by each looks remarkably the same,” says Suzuki. “The body somehow makes right and left ventricles in the same way from different sources.”

Suzuki has found an answer – one which may lead to development of targeted drugs to treat right ventricle diseases, such as pulmonary hypertension, which is difficult to manage and often quickly fatal. On the other hand, common hypertension (high blood pressure), which occurs in the left ventricle, is very treatable.

He published his findings in Hypertension late last year, which he also just presented at the Experimental Biology 2011 meeting in Washington D.C.

Suzuki found a very subtle difference in the cell signaling mechanism that is needed to activate GATA-4, a transcription factor that regulates genes involved in heart function. GATA-4 is known to be involved in enlargement of cardiac muscle cells when blood pressure increases, and the right ventricle initially responds to this pressure overload by thickening the ventricular wall to strengthen muscle contraction – but this cardiac hypertrophy event is following by a transition to thinning of the ventricular wall and heart failure.

He and his colleagues discovered that the mechanism that activates GATA-4 is different between the left and right ventricles.

“By knowing this, it may be possible to tailor how GATA-4 is regulated on the right, without affecting its function on the left,” Suzuki says.

This is a novel finding in cardiac research – which may be viewed as somewhat surprising since Suzuki’s laboratory is the only one at GUMC that studies heart function.

Suzuki, who came to GUMC from Tufts University in 2004, had anticipated a cardiac research center to be established on the campus, but those plans quickly changed when GUMC partnered with MedStar and consolidated cardiology at Washington Hospital.

Still, he is happy to be at GUMC, where he did a second postdoctoral research program in 1995 after his first postdoc at the University of California, Berkeley. He received his PhD at the Medical College of Virginia, located in the state he first came to as a high school exchange student from his native Japan.

“We are doing very well in our little laboratory,” Suzuki says with a laugh. He works with a team of researchers supported by two National Institutes of Health grants: Lucia Marcocci, PhD, a visiting professor from the University of Rome, Chi-Ming Wong, PhD, a research assistant professor, Geetanjali Bansal, PhD, a research assistant professor, Brent Gilmore, MD, an anesthesiology resident, and Yasmine Ibrahim, MSc, a PhD student.

The team also studies smooth muscle cells, and is decoding signal transduction mechanisms in asthma, which occurs in lung cells.

But it is right ventricle failure that has caught his – well – heart. “Pulmonary hypertension is a devastating disease without a cure, and by understanding these tiny differences in cardiac cells, we dream of making a big difference,” he says.

By Renee Twombly, GUMC Communications