In his lecture, Dr. Lindner discussed UVA’s role in developing and implementing contrast ultrasound, a technique where microbubbles are injected into a patient’s bloodstream to improve imaging in ultrasounds. “This is a UVA story,” explains Dr. Lindner. “Early first-in-human studies, safety and optimization research, and large clinical trials are all UVA work.” He also discussed how UVA continues to lead in the field by advancing new applications for contrast ultrasound and microbubbles. Dr. Lindner and other researchers are using the technology to deliver medications or genes to specific organs, diagnose disease with greater precision, and further improve the imaging potential of ultrasound methods.

Presenting to a lay audience presents unique challenges beyond making advanced science understandable to those without research experience. “You can often predict the questions a scientist will ask,” Dr. Lindner says. “Audiences who are less involved with day to day science will often ask unexpected, prescient questions that can really challenge you.” The Q & A period covered topics ranging from technology commercialization to safety considerations.

The U Ask, UVA Answers series continues February 8 with a presentation by Kelsey Johnson, PhD, from the Department of Astronomy.

The Weyman Award which is named for one of the early pioneers of cardiac imaging, generally receives 40-50 manuscripts from applicants. Only the top four are invited to compete and present at the ASE meeting ASE meeting. Dr. Morello presented his work in front of thousands of other scientists. “The ASE meeting lasts three days, and these presentations are its scientific highlight,” says Dr. Lindner. Dr. Morello joins 12 Weyman Award finalists mentored by Dr. Lindner in the past. “Dr. Morello joins a 20-year history of people from our lab receiving this award, which recognizes the best science in echocardiography,” Dr. Lindner explained. Receiving the award provides not only a monetary prize, but funding for travel to the European Society of Cardiovascular Imaging and the Japanese Society of Echocardiography meetings where Dr. Morello will present his work globally.

Dr. Morello’s presentation was titled “Cavitation-facilitated Augmentation of Myocyte Gene Delivery with Adeno-associated Vector-9: A Bioengineering Strategy to Address Clinical Gaps in Cardiac Gene Therapy.” In his talk, Dr. Morello described a new method for safely delivering gene therapies to tissue in the heart. Many gene therapies rely on using a modified virus, utilizing the virus’ natural ability to transfer DNA into cells to to correct a genetic flaw in the patient. This process is safe and effective in other organs, but the quantity of virus needed to treat genetic conditions in the heart exceeds safe level, a problem Dr. Lindner recognizes through his work as the Co-Chair of an NIH committee that oversees safety of gene and cell therapy trials. He and Dr. Morello have shown that  ultrasound-mediated vibration of microbubbles inside the heart blood vessels allows the virus to better penetrate into the heart’s tissues. More efficient viral delivery allowed Dr. Morello to lower the viral dose, resulting in a safe and effective treatment. He optimized the treatment conditions in mice before continuing his work at the Oregon National Primate Research Center. There, he showed that his methods were safe in non-human primates. He also showed that his methods are capable of partially reversing hypertrophic cardiomyopathy in mice that were developed by researchers in the CVRC.

The other research highlight of the ASE conference was the Brian Haluska Sonographer Research Award. The award recognizes sonographer-led research, where non-physicians are the study’s primary investigator. Gholson’s winning presentation, “Rapid Acceleration of Aortic Stenosis Progression in Echocardiography After Acute Coronary Syndrome,” went through the same vetting process as Dr. Morello’s, and involves a monetary award.

Gholson joined Dr. Lindner’s lab in 2022, becoming the team’s resident specialist in imaging the heart with ultrasound. Her research studied patients with progressive aortic stenosis, a condition that results in calcification of the heart valves over time. She studied over 15,000 records and images to build a database of patients with aortic stenosis. Gholson meticulously re-measured all the data points in her database and worked with collaborators to show that when one of these patients suffered a heart attack or similar cardiac event, the rate at which their valves thickened increased and did not return to the baseline rate of aortic stenosis progression for approximately two years. “Between collecting and re-analyzing all the data, I often left work cross-eyed to get what we needed,” joked Gholson.

Identifying cardiac stress events as the sole culprit for the increased rate of valve thickening was a statistical challenge. Gholson and collaborators were able to able to statistically prove that the increased rate of progressive valve thickening and restriction to opening was triggered by the heart attack. Other members of the laboratory are working on the molecular signals that get released after heart attack that are responsible for valve changes. Gholson is extending this research into other conditions to see whether damaging cardiac events accelerate disease progression. “This really is the tip of the iceberg,” she explained. “There are a lot of other conditions where we can make a difference in patient care.”

“The competition for both awards was incredibly fierce,” says Dr. Lindner. “This year had the highest quality science I’ve seen in both categories, so I’m extremely proud of Matteo and Bethany’s work.” Gholson credits the familial atmosphere at UVA for her success. “Recognition for this award really belongs to the entire research group. Our team shaped the project throughout, and I’m deeply grateful to Dr. Lindner, our collaborators, and our colleagues for their support, guidance, and partnership,” she stressed.

A multidisciplinary team led by Jonathan Lindner, MD, the Frances Myers Ball Professor of Medicine and Vice-chief for Research in the Cardiology Division, was awarded a $3.5M R01 grant from the NIH to develop novel therapies for preventing aortic stenosis. The research team will use advanced non-invasive imaging in pre-clinical gene-modified models and in humans to evaluate fundamental questions on the pathobiology of aortic stenosis involving shear stress, platelet adhesion, and platelet signaling. The team will use this information to develop novel therapies that can prevent progressive valve thickening and calcification once early abnormalities are detected. Collaborators on the team include Jose Lopez, MD of BloodWorks NW who specializes in platelet biology, and James Thomas, MD, of Northwestern University who specializes in valve hemodynamics. These studies led by Dr. Lindner, who just recently returned to the University of Virginia after 16 years, compliment other NIH-funded studies evaluating the role of platelets and thrombo-inflammation in atherosclerosis and microvascular thrombosis.

View the article at the SOM website