Medical student’s research investigates the heart of the matter

When Katie Hardin was considering medical schools after studying biomedical engineering with a concentration in nanotechnology as an undergraduate, it was the extensive research focus of the Virginia Tech Carilion School of Medicine (VTCSOM) that won her heart. Her research into calcium deposits in the cardiac intercalated disc may be a step toward preventing lethal arrhythmias in the future. 

“I think it’s a very unique opportunity to get to do such an in-depth project in medical school. Typically, medical students don’t have as much dedicated research time, and if I had to do it all in just one summer, like at many schools, I would not have gotten nearly as far as I have,” said Hardin, a fourth-year medical student who will graduate in May. “That was a big factor for me coming here.”

VTCSOM’s curriculum weaves student research throughout all four years of the program. All students are expected to a conduct an original, hypothesis-driven research project before graduation.

Hardin was one of nine students to receive a Letter of Distinction for her research, and she will provide an oral presentation at VTCSOM’s annual Medical Student Research Symposium, held from noon-5 p.m. March 24. Her mentors were Gregory Hoeker, research assistant professor at Fralin Biomedical Research Institute at VTC, and Steven Poelzing, a professor and cardiovascular researcher at the institute and co-director of Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program.

“I have been very impressed with how quickly Katie developed her technical skills, including sample preparation, image acquisition, and analysis for three different imaging modalities. She has never hesitated to take on new challenges, and her contributions have been critical for moving this new project forward quickly,” Hoeker said. “Katie also is a very effective communicator. Her research presentations have always been a model for other trainees in the lab.”

After her undergraduate studies at Boston University, Hardin did two gap years focused on heart failure and transplant research at Massachusetts General Hospital.

“That is when I was first exposed to cardiac research and definitely developed my passion for it,” she said. “That was a huge reason why I chose to do this project in medical school.”

Hardin conducted physiology testing and clinical trials at Mass General, thinking she wouldn’t be interested in returning to the lab work of her undergraduate days during medical school. When she began at VTCSOM, however, she found she was drawn back to the opportunity to get behind the microscope. 

“I felt that this is likely one of the last times in my medical career I’ll have time to devote to in-depth basic science research,” she said. “Most medical school students don’t get that chance, and while it is very time-consuming, I wanted to make the most of it.”

Hardin looked into cardiac research being done across Virginia Tech, at the Fralin Biomedical Research Institute, and at Carilion Clinic, and she found that the Poelzing lab was conducting molecular biophysical work in relationship with heart rhythms that interested her.

Prior research at the lab had found that when calcium levels were decreased in the heart, there was reduced cell-to-cell adhesion and increased intermembrane spacing in the intercalated disk, particularly within the specialized nanodomain between individual heart muscle cells termed the perinexus. The disruption of the cell-to-cell adhesion and associated structural changes may slow cardiac conduction of the electrical impulse across the heart that triggers muscular contraction for pumping blood and potentially lead to lethal irregular patterns of electrical activity, or arrhythmias, that in extreme cases can lead to sudden cardiac death. 

“In this exciting new area of research, we are investigating a potential new role for the specialized pores in the membranes of heart cells that allow calcium to enter the cell, triggering muscular contraction – what are called voltage gated calcium channels,” Hoeker said. “Our new hypothesis is that these calcium pores or channels also serve to modulate the specialized nanodomains between cells as an adaptive response to conditions of stress or increased cardiac demand.”

Hardin learned two types of super-resolution microscopy to identify and quantify novel subpopulations of these calcium channels in or near the perinexus. She followed up by using transmission electron microscopy to test how modulating calcium channel function in whole-heart studies alters the structural changes of the perinexus in response to cardiac stress.

Hoeker said continuation of this work could lead to a better understanding of exercise intolerance associated with aging, improvements in heart medications, and may reveal novel targets for new antiarrhythmic therapies.

“Katie’s work can pave the way for the development of next generation beta blockers, a medication currently taken by approximately 30 million people in the United States,” Poelzing said.  

After an estimated 800 to 1,000 hours in the lab, Hardin is not quite ready to step away from her research. She plans to examine different calcium up-regulating and down-regulating, or blocking drugs, and how that affects the cardiac conduction velocity. When conduction velocity “goes haywire,” different troublesome arrhythmias present themselves.

Hardin received an American Heart Association Student Scholarship for her project and presented her research at the Biophysical Society 66th Annual Meeting in February 2022 in San Francisco. Despite all the success in cardiac research, she plans to pursue otolaryngology, head and neck surgery, for her residency. She is sure, however, that the lessons she took to heart will translate to her new field.

“I have a lot of basic science research skills now, and I didn’t know how to do any of these techniques prior to VTCSOM,” she said. “I think the research training that is provided to students is an amazing opportunity. I am really exciting to get to use that in the rest of my career.”