The heart of the matter
A professor’s journey from India to America led him to a surprising discovery about how a genetic disease affects people from his home country
By Erinn Connor
The state-of-the-art lab on the top floor of the new Center for Translational Research and Education is nearly 9,000 miles away from Pattiveeranpatti, Tamilnadu, India. Both are home to Dr. Sakthivel Sadayappan, and they show how far he’s come in his short time at Loyola University Chicago.
Sadayappan, an associate professor of cell and molecular physiology, and his colleagues study one specific muscle protein called myosin binding protein-C, found in skeletal and cardiac tissues. But his interest in the protein is even more specific: mutations in the cardiac myosin binding protein-C (cMyBP-C) gene are associated with hypertrophic cardiomyopathy. This genetic disease, which causes abnormal thickening of the heart muscle, is the leading cause of sudden death in people under the age of 30, particularly young athletes.
“It’s something where people have no symptoms, have no idea they’re carrying this mutation that could potentially kill them,” says Sadayappan. “From the beginning we’ve been looking into not only what causes this sudden cardiac death but what population is most at risk, and eventually, what we could do to treat it.”
When he was a young boy in India, Sadayappan did not think that looking for the cause of a complicated heart disease would be his destiny. In his hometown, the most likely occupation for men was coconut farmer. But his parents urged him to pursue bigger dreams outside of his small town of 7,700.
Sadayappan was still intrigued by the plant life of his farm home, so he got an undergraduate degree in botany. He went on to explore his interest in cardiovascular research and earned his graduate and postdoctoral degrees in biochemistry. He made the move to the United States (with a four-year stopover in Germany), where he could further nurture his research interests.
In 2009 he established his lab at Loyola and has since been dedicated to studying heart failure and the cMyBP-C. Sadayappan was named 2012 Junior Scientist of the Year at the Stritch School of Medicine for his novel findings.
His research so far on the protein has shown that it breaks apart during a heart attack. This means that a non-mutated cMyBP-C is vital to normal heart function and normal heart muscle. “It’s a muscle protein that controls how many folds of muscle the heart can generate, which helps the heart to contract properly,” Sadayappan says.
A groundbreaking piece of his research took Sadayappan back to his home country. Through collecting blood samples from all over the world, he and his colleagues found that one in 25 people from India and South Asian countries carry a mutation of the gene that codes for cMyBP-C, making them susceptible to hypertrophic cardiomyopathy and heart failure. In the mutated gene, 25 DNA base pairs are missing. As a result, the tail end of the protein is altered.
“South Asians have a 50 percent greater mortality rate in the United States from cardiovascular disease,” says Sadayappan. “Like anyone with heart disease, it’s a combination of lifestyle influence, risk factors, and genetics. But with South Asians the genetic aspect plays a much bigger role.”
Now the goal is to figure out the exact pathology from the mutation to hypertrophic cardiomyopathy and to develop potential drug therapies to treat it. For this Sadayappan has received funding from the National Heart, Lung, and Blood Institute, the American Heart Association, and the pharmaceutical industry.
As part of this research he’s recruiting South Asians from the Chicagoland area and other parts of the United States to be tested for the cMyBP-C mutation. Sadayappan’s lab is gathering samples from the United States instead of going abroad—about 4 million people of South Asian ancestry live in America. Sadayappan and his lab members go into local community centers and educate people on the gene and what the mutation could potentially cause.
For those who test positive, they’re offered an echocardiogram at Loyola University Medical Center to see if there is any heart muscle damage. They are also given the opportunity to discuss risk factors that may increase their likelihood for suffering a heart attack.
Recently, Sadayappan traveled back to his alma mater, American College in Madurai, India. There he gave a seminar to current students who were in the same shoes he was in 25 years ago—studying botany. He told the students of the wide variety of career opportunities open to them after graduation. Returning to visit his alma mater, he says, was “certainly one of the happiest days of my life.”
Sadayappan’s own life story and research journey should prove to be plenty of inspiration for students back in India and for those under his tutelage in his lab at Loyola.
“It’s taken 17 years to get here and to gradually piece together what we know so far about this protein and how it gets mutated,” he says. “We’re hoping that we can not only understand the mechanism behind hypertrophic cardiomyopathy but also have ways to treat it and reduce the number of sudden deaths.”