Cracking the code

State biology Professor Shaad Ahmad received the Scientist Development Grant from the American Heart Association to learn more about the genetics behind congenital heart defects.

When it comes to heart problems, you might first think of high blood pressure, heart attacks or coronary heart disease — conditions that may stem from years of unhealthy habits. But for some, heart troubles can be present from birth.

An estimated 2.4 million American children and adults live with some kind of congenital defect in their hearts, according to the U.S. Centers for Disease Control and Prevention. Small interior holes, missing portions or poorly formed parts are just some examples of congenital heart defects (CHDs). Symptoms can appear soon after birth or years later, and the condition can be non-critical, debilitating or fatal.

And the exact cause? Unknown.

But scientists at Indiana State University are searching for an answer.

Shaad Ahmad, assistant professor of biology at Indiana State

Shaad Ahmad, assistant professor of biology, is leading a team of researchers to learn more about the genetics behind congenital heart defects. In support, the American Heart Association awarded Ahmad with a Scientist Development Grant. The $231,000 award supports promising beginning scientists and their important heart research, like Ahmad’s.

With this grant, Ahmad and his team are studying how DNA directs heart development and how faulty regions of DNA could lead to CHDs. Their findings might eventually help doctors detect and mitigate patients’ susceptibility to CHDs. But their research also has another long-term goal.

“What we really want to do — and this is probably 30 years in the future — is to be able to take some of your cells and if you have a bad ticker, grow you a completely new heart,” Ahmad said. “But in order to do that, we have to understand the entire genetic regulatory network that gives rise to the heart.”

That network includes hundreds of interacting genes — specific regions of DNA — that work together to develop and maintain your heart tissue. Many of those genes instruct, or “encode,” the creation of particular proteins, the molecular units that are the building blocks of your body and facilitators of all sorts of cellular activity (for your heart, proteins determine the structure of the organ, facilitate cardiac contractions, transport oxygen in blood and much more).

Although your DNA has thousands of protein-coding genes, only some genes are turned “on” and actively create proteins that will perform their important functions. Other genes are turned “off.” What flips the genetic switch? Other proteins, of course. These are called transcription factors — the focus of Ahmad’s study.

Ahmad’s research explores “Forkhead” genes that encode transcription factor proteins that switch genes “on” or “off” as the heart forms. It’s a critical process to get right for proper heart development. But when some Forkhead genes are mutated (or corrupted), they fail to produce proteins that can correctly activate or inactive other genes. The ultimate result? Congenital heart defects.

Shaad Ahmad talks to students.

“To a certain extent, that was what was known — that (Forkhead genes encode) transcription factors and that if they are mutated, you’d have different types of heart defects. But we didn’t precisely know what was going wrong,” Ahmad said. “What we’re trying to do with this particular grant is get a molecular understanding.”

Ahmad and his team aim to continue to discover precisely which genes and processes are regulated by Forkhead transcription factors. For example, they believe they’ve found about 20 genes regulated by these transcription factors that may play a role in cardiac progenitor cell division, a process that turns foundational cardiac cells into different types of heart cells.

“What we want to do is build up the entire genetic network that’s downstream of these Forkhead genes that are involved in getting you the proper heart,” Ahmad said.

Ahmad uses a surprising model for studying heart development — the fruit fly, whose heart has “many of the same genes and regulatory pathways” as the human heart, making it the perfect test subject for Ahmad’s current studies.

“Then we move on from flies to mice, which are to developmental biologists little furry humans, and then we shift to primates and eventually humans. Note, however, that I said that this is roughly, optimistically, 30 years in the future,” Ahmad said. “What our research may do at this point in time is serve to give us diagnostic cues (for congenital heart defects or late-onset heart disease).”

Although engineering a human heart to replace damaged ones is still many years away, it starts with building a comprehensive understanding of the genetics behind proper — and improper — heart development.

“I’m excited, I’m thrilled,” Ahmad said about receiving the American Heart Association’s grant in support of his research. “I think it’s a very interesting project and I think the data we intend to acquire from this will help the biomedical and medical communities.”

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