Bringing the heart back to life
By Kimberly Eaton
Biomedical science can generally be broken down into two key areas: making new discoveries and developing new ideas. But for Mark Pepin, it began with a passion for solving problems.
“It’s a different way to approach the biomedical sciences,” said the 31-year-old South Carolina native. “As engineers, we tend to focus on the tools that make scientific discoveries possible, as well as their application to real-world problems.”
It was this passion for solving puzzles that led Pepin through his training in engineering, first with a bachelor’s in chemical engineering from Clemson University, followed by a master’s in biomedical engineering from University of California Davis. It was here that he recognized a strong desire to help patients as the missing puzzle piece in his training. The “secret ingredient” of biomedical science: medicine. He decided to develop his interest in both medicine and biomedical research as an MD-PHD student at UAB.
“It’s surprisingly hard to find universities that offer a balance of clinical competencies with cutting-edge research on campus,” Pepin said. “To be honest, UAB wasn’t on my radar when I started to apply, but when I arrived for the interview I found the perfect fit: innovative patient-centered research fully integrated within the clinical facilities. It is amazing.”
Through this dual-degree MD-PhD program, Pepin completed his first two years of medical school, and then transitioned into his PhD program in biomedical engineering. Although Pepin assumed he would look into muscular skeletal physiology and exercise, which was his background, his interests shifted to cardiology during his first two years of medical school.
“The heart is a more advanced machine than anything man-made; it is designed from materials that are alive, grow, and respond to their surroundings,” he said. “It really spoke to me as both a chemical engineer and medical doctor that we can study this amazing pump to treat patients with severe illness.”
That was Pepin’s introduction to cardiovascular medicine in science. From there, he chose Dr. Adam Wende’s lab because, among many reasons, it had “really cool tools” that were used to understand what goes wrong with the heart and why it fails.
The Wende Lab’s research focus is on understanding how alterations in the heart’s fuel supply can both cause heart failure and be disrupted in the heart when it fails. It studied these “metabolic causes and consequences” of heart failure, and Pepin’s project focused on epigenetics.
In broader terms, Pepin described his research using the analogy of a cookbook.
“In every cell or tissue, including the heart, there is a cookbook of DNA. The recipes used depends on the needs of the cell and the ingredients available to it. Epigenetics is a way of controlling which recipes of genes are available in this cookbook to determine how that cell functions.”
For Pepin’s project, he acquired human heart samples from UAB patients who had end-stage heart failure, “with their permission, of course!” They then looked at how the genes were being expressed inside the tissue, but also what the epigenome was doing and how the genes were being regulated in patients with heart failure.
“That was the core of my project – trying to understand how heart failure is associated with an epigenetic change called DNA methylation,” Pepin said. “It’s a modification that is known to regulate how recipes, or genes, are used. We were the first lab to show that DNA methylation is linked to how these hearts use different fuel sources for energy.
“When someone develops heart failure, as healthcare professionals we have treatments for patients based on what is causing their disease. My project helped to show that patients with heart failure display different epigenetic patterns that hopefully can be used to design better treatments in the future. At least, that’s the goal,” he added.
Pepin completed his Ph.D. in April 2019, and is now pursuing a postdoctoral fellowship in Germany.
“Despite having studied the theory and mechanism of heart failure for the past 6 years, seeing people suffer from it completely changed my understanding of it,” Pepin said. “Every patient is different. Some respond well to our current medicines, but others do not. This observation is what really excites me about my research. There are many ‘flavors’ of heart failure, and I think epigenetics will help us understand them better. Ultimately, we need medicine to treat each patient individually using therapies that address the underlying cause of disease.”
Pepin’s goal is to become a cardiologist and epigeneticist, which will require six more years of medical training. Regarding his long road of training ahead, he responds jokingly, “Is it still school when you’re having fun and making a difference? I already love what I get to do.”
Pepin hopes to start his own lab that studies epigenetics as a means of regenerating the heart.
“Currently, there is no way to fix a broken heart,” he said. “I want to change that.”