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How does a human heart develop? Whitney Edwards thinks about this question a lot.

“We have puzzle pieces, but we don’t have the whole story,” Edwards says.

Here’s what we know: As a fetus grows, its cells carry the blueprint for building the heart and other organs. They start by forming a simple tube of muscle, which elongates and twists to create two early heart chambers. Walls divide each chamber, forming the two atria above and two ventricles below. Finally, the heart’s valves and vessels develop, enabling blood to circulate throughout the body.

By the middle of pregnancy, all the heart’s basic structures are in place. Then, phase two begins: those valves, vessels, and chambers mature; their walls thicken; and the heart strengthens to handle increased pressure from the circulatory system. After birth, it grows again to support the surge of blood needed to fuel a rapidly developing body.

But we’re missing a lot of details about what drives those processes.

Here’s what we don’t know: what guides chamber formation, how heart muscle cells mature, and what drives the formation and strengthening of valves and vessels.

Edwards is determined to fill those gaps. Because the more researchers understand how the heart forms step by step, the better chance Edwards and her lab in the UNC Department of Cell Biology and Physiology have at uncovering when — and why — congenital heart disease begins.

Congenital heart disease is the most common birth defect, affecting nearly 1% of newborns — about 40,000 babies each year in the U.S. In more than half of cases, doctors can’t identify a cause. Severity ranges from small holes that heal on their own to serious malformations requiring multiple surgeries. Some people live full lives with minor defects while those with more complex conditions often face shorter lifespans.

 “It’s like this huge black box,” Edwards says. “We have no idea why most people have a congenital heart defect. And, for me, the heart is one of the most interesting and structurally complex organs in the body. I want to know how it forms — and where things go wrong.”

Diagnosing the problem

Think of the heart like a car engine: countless tiny parts — pistons, rings, valves, spark plugs — must work in harmony. When an engine falters, the many processes taking place beneath the hood make it difficult to pinpoint the exact cause.

Edwards approaches congenital heart disease the same way, studying how developmental misfires accumulate inside an organ that’s building itself in real time. Her team focuses on a chemical modification that occurs when enzymes attach fats to proteins. These attachments help proteins reach the right place in a cell and perform the right job.

Edwards wants to understand how these enzymes guide normal heart development and what happens when they don’t. Her lab uses two approaches.

First, they isolate heart muscle cells in a petri dish and disrupt enzyme activity to see how the cells respond. When fats can’t attach to proteins, the heart muscle cells stop contracting.

“That’s just one enzyme, and there’s a lot of other enzymes we could target,” Edwards shares.

Second, they use genetic editing to delete this enzyme at specific times during development. When they do, severe congenital heart defects emerge. Most notably, the ventricles, which are the chambers responsible for pumping blood throughout the body, don’t form properly.

The team also identifies which proteins receive these fat attachments and explores how cell metabolism — the reactions that allow a cell to grow, reproduce, and maintain its structure — shapes this process.

“If we can map out these pathways, we might be able to develop treatments for congenital heart disease in the future,” Edwards says. “But we are at the cusp of trying to address this.”

Just as a mechanic might trace an engine problem back to a single faulty component or an interaction between parts, Edwards aims to map how molecular misfires ripple through the developing heart. By teasing apart which enzymes, pathways, and metabolic processes are essential, and what happens when one piece slips out of sync, her team hopes to reveal why small disruptions can have far-reaching consequences.

Pursuing her own pathway

Like her research, Edwards’ path to science wasn’t straightforward, and it began far from a lab bench. All four years of high school, she performed in plays and immersed herself in creative pursuits, enough that she seriously considered majoring in drama.

But during her first year of college, a chemistry course changed everything. The professor had previously worked in the biotechnology industry. That was Edwards’ first exposure to a scientist who built a career outside academia.

“I didn’t know that was even a thing people did,” she says with a laugh. “I think it was her combination of teaching abilities and connecting with these challenging aspects of science that made me think this was a real career path I could take.”

Edwards switched her major to biochemistry and, after graduating, spent a year working for a medical company. The work was repetitive, and she didn’t have room to grow. She wanted less sample prepping and more freedom to ask big questions — which meant pursuing a PhD.

Early in her graduate studies, she became passionate about developmental biology. What captivated her then is the same idea that fuels her work today: that a single cell can become an entire organ.

“It’s crazy that we even exist,” she says. “The complexities of making cells and different cell types and then creating this 3D functional shape from them. How does that actually happen?”

Humanizing science

For all the molecular puzzles Edwards works to piece together, one experience brought the stakes into sharp focus.

She recently attended an investigators’ meeting with Additional Ventures, a foundation dedicated to studying single-ventricle diseases, among the most severe forms of congenital heart disease. These are the cases where newborns undergo reconstructive heart surgery within days of birth, returning to the operating room again as toddlers, teenagers, and adults.

Parents spoke about the moment their child was diagnosed and the series of surgeries that followed. Adult patients described navigating school, jobs, relationships, and daily life with a heart that has been rebuilt multiple times. What struck Edwards most was not just the physical and emotional burden but the financial struggle of undergoing major heart surgery again and again.

This was the first time she’d heard patients and families share their stories directly.

“It was incredibly eye-opening,” she says. “You don’t always get that opportunity in basic science. For me, it really amplified how these are lifelong diseases.”

It made Edwards think about where she could focus her efforts. These diseases are incredibly complex. Patients with single-ventricle defects may also have problems with their valves or the vasculature. So understanding even one piece of ventricular development could eventually make a difference.

“When you’re in basic research, you may not get the chance to interact with patients,” she says. “But hearing their stories — hearing what they’ve been through and how medical interventions have extended their lives — it absolutely informs our research directions. It reminds us that what we’re doing matters.”