When Kathleen Martin, PhD, gives the Alexander W. Clowes Distinguished Lecture at the 2022 Vascular Research Initiatives Conference (VRIC) in May, she’ll be discussing research that the late Clowes himself studied. “He’s really the father of this field,” she said. “I’m pleased to be able to build on what he founded. My research is very much in the same field that he started.”
Martin said Clowes, a renowned surgeon-scientist who contributed greatly to VRIC, established the first models of vascular injury after surgical interventions. He died in 2015 and the VRIC lecture named for him was created a few years later.
This year’s conference theme is “Translational Immunology and Cardiovascular Disease.” Martin will discuss the plasticity of smooth muscle cells (SMC), which are “incredibly versatile and almost stem cell-like in nature” in that they can change their phenotype dramatically and are highly proliferative, forming new lesions after vascular injury. “Dr. Clowes outlined how this happens,” said Martin.
Her research lab at Yale University in New Haven, Connecticut, wants to define the cellular signaling and epigenetic mechanisms that regulate vascular SMC function in intimal hyperplasia, atherosclerosis and transplant vasculopathy. Understanding how these cells dramatically alter their phenotype may provide new insights for treatment and prevention of vascular disease. SMCs make up the muscular layer of blood vessels, allowing them to contract and relax, and help control blood pressure, vascular tone and blood supply. Her lab’s major focus is studying how SMCs can so dramatically change their state, from a healthy contractional phenotype to cells that lose their ability to contract and can potentially become fibrotic. Her lab has identified novel master regulators of SMC phenotypic switching.
This smooth muscle plasticity impacts many vascular diseases, she said, including atherosclerosis—“the reason we need so many vascular interventions.” Other diseases include aneurysms, intimal hyperplasia, transplant vasculopathy, vascular calcification and more. It also affects the interventions—stenting, ballooning, bypass procedures, grafts and others—performed to treat vascular diseases.
“This smooth muscle plasticity is relevant to a wide range of cardiovascular diseases, as well as transplant pathology,” said Martin. Science has come a long way toward eliminating outright organ rejection, but chronic transplant rejection is a major concern and cause of death with limited treatment options, she said. Her recent work has suggested new possibilities. “If we can contribute something that could help transplant patients […] we’d be thrilled,” Martin added.
Martin, who trained as a cell biologist, got her first research position in vascular surgery at Dartmouth Medical School in Hanover, New Hampshire, where she learned of the challenges vascular surgeons face in treating vascular disease. In fact, there, she and SVS members Richard Powell, MD, and Eva Rzucidlo, MD, worked together on stent therapeutic drugs in SMC. “It really opened up this new research direction to me,” she said. “Most cells don’t have this ability to completely change their fate. I found it fascinating.”
She misses that day-to-day contact with vascular surgeons, though she still collaborates with SVS member Alan Dardik, MD, and many other physician-scientists. “I’m excited to get feedback from the SVS community at VRIC, and eager to hear their suggestions,” she said.
VRIC takes place Wednesday, May 11, at the Sheraton Grand Seattle Hotel, Seattle—the day before and in the same venue as the American Heart Association’s Vascular Discovery Conference. To learn more and to register, visit vascular.org/VRIC22.