Gregory Payne, M.D., Ph.D.Gregory Payne, M.D., Ph.D., associate professor of Medicine, has been named the latest recipient of the school’s Featured Discovery award. This recognition celebrates notable research contributions made by faculty and highlights the impact of their scientific advancements.
His study, “Spatial transcriptomic approach to understanding coronary atherosclerotic plaque stability,” was recently published in Arteriosclerosis, Thrombosis, and Vascular Biology.
In this study, Payne and his team used cutting-edge technology called spatial transcriptomics. Spatial transcriptomics is a technique that maps gene activity within tissues to understand how different parts of the tissue function and interact. This allowed them to examine the exact location and activity of different cells inside artery plaques from patients who had passed away. By comparing stable plaques with unstable ones, the team found important differences in how cells behave and communicate with each other.
“When we first started this investigation, spatial transcriptomics was still the “new kid on the block.”’ Payne stated. “Atherosclerosis is a notoriously complex disease, involving a wide range of cell types and multiple factors that contribute to its onset, progression, and eventual complications like plaque rupture and heart attacks. So when we had the chance to apply this cutting-edge technology to such an old and challenging problem, we jumped at it”.
They discovered that certain cells inside the plaques—like immune cells and muscle cells—change their roles and locations in ways that may make plaques more likely to burst. These changes were linked to inflammation and clotting, two major risk factors for heart attacks.
What compelled you to pursue this research?
Cardiovascular disease, particularly coronary artery disease, remains a leading cause of death in the United States. As a cardiologist, this is a critical issue I confront regularly in my clinical practice, but it is also deeply personal, as members of my own family have been affected by the devastating consequences of this disease. Therefore, I've long been fascinated by the question of why some patients develop coronary artery disease and suffer heart attacks.
For decades, research in this area has relied heavily on in vitro and animal model experiments. While these approaches have yielded important insights, they often fail to fully capture the life-threatening events that occur in patients. Recent advancements in spatial biology and spatial transcriptomics gave our team a unique opportunity to explore the underlying mechanisms of coronary artery disease directly in human tissues. These technologies have finally allowed us to ask and begin to answer critical questions that were previously out of reach.
What was your most unexpected finding?
For years, research has suggested that smooth muscle cells, traditionally known for regulating arterial resistance, can change function during the development of coronary artery disease and atherosclerosis. However, direct evidence of their clinical significance was limited.
We were surprised to find that these altered smooth muscle cells were not only present but also abundant in patients at risk for heart attacks. Even more striking, these cells exhibited a distinct molecular signature unlike any other cell type and were associated with changes that likely drive disease progression.
How do you feel your research will impact the science community?
Our research underscores the transformative power of spatial transcriptomics, particularly in vascular biology, by providing an unprecedented view of cellular changes driving coronary artery disease. By applying this cutting-edge technology to human tissues, we are not only advancing our understanding of disease progression but also setting a new standard for how we investigate complex cardiovascular conditions.
Beyond its scientific discoveries, this work will serve as a publicly available resource for basic scientists, enabling them to explore novel mechanisms that could delay or even resolve coronary artery disease. It offers an invaluable dataset for generating new hypotheses, guiding future research, and accelerating the development of targeted therapies.
Additionally, our findings validate the utility of animal and in vitro models for studying cardiovascular disease while also highlighting their limitations. By providing a direct comparison between experimental models and human pathology, we hope to refine preclinical research approaches and enhance their relevance to human disease.
Ultimately, we believe this study will not only push the boundaries of cardiovascular research but also inspire new applications of spatial biology in other fields of medicine.
When did you know you had an important discovery?
Honestly, when we began reviewing the first tissue slides, we knew we had discovered something new and important. The excitement among the team was palpable—we all recognized that we had uncovered something truly groundbreaking.
What do you find makes the science community here unique?
The scientific community here is incredibly collaborative and genuinely eager to support one another. As biomedical researchers and physician scientists at a southern academic institution, we occupy a unique vantage point—we are closely connected to the real-world challenges faced by our patient population, which gives our work immediate relevance and urgency. At the same time, we benefit from the resources, expertise, and institutional support needed to make truly groundbreaking discoveries. That combination of purpose and possibility makes this an especially dynamic and impactful place to do science.
Featured Discovery
•
April 21, 2025