Hypertension, high blood pressure, affects approximately half of Americans over the age of 18. Persistent high blood pressure can contribute to heart attack, stroke, vision problems, and kidney disease, making it an important target for pharmaceutical development. “Many patients with high blood pressure are left with treatment-resistant hypertension,” says Araujo. ” There is a critical need to identify new ways of treating hypertension, and this requires a better understanding of pathological mechanisms.”

Blood pressure is controlled in part by smooth muscle cells inside our blood vessels, which can tighten or relax the vessel to control blood flow. “I am working on a fundamentally new mechanism for blood pressure regulation. This mechanism involves a well-known receptor called mineralocorticoid receptor, which alters ion channel activity and regulates smooth muscle contraction,” Araujo explains. To accomplish her objectives, she will use a combination of gene editing techniques, measurements of the electric currents inside cells, and super-resolution microscopy capable of observing individual proteins at the plasma membrane. Running these experiments in model systems and human samples with and without hypertension will allow Araujo to uncover new mechanisms of blood pressure regulation and possibly unlock new treatment options for hypertension.

The AHA Postdoctoral Fellowship is a prestigious, highly competitive award. “It’s an important milestone in my career, and I’m profoundly grateful for the training and support provided by the Sonkusare lab, as well as the research environment at the CVRC,” says Araujo.

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.

Eichert won an Early Career Poster Competition award, selected from amongst the conference’s 487 poster presenters. His presentation, “Growth Differentiation Factor 11 Regulates Cardiomyocyte Cycling After Myocardial Infarction,” discusses work investigating how heart muscle recovers from a heart attack. Specifically, Eichert hypothesized that cardiomyocytes release a compound, Growth Differentiation Factor 11 (GDF11), during cell division after a heart attack to prevent the muscle’s ability to contract from being lost. He showed that secreted GDF11 may prevent cell proliferation after heart attacks, which correlated to poorer heart function.

Murillo’s presentation, “Pharmacological Inhibition of DYRK1A Induces Cardiomyocyte Cell Cycle Activity,” was selected to be one of ten talks given in the Early Career sessions. He spoke about using a drug to increase the ability of cardiomyocytes to divide and proliferate, which is a limiting factor in the heart’s ability to heal after trauma. The Wolf team has previously shown that removing a particular protein, dual specificity tyrosine phosphorylation regulated kinase 1A, from the cell increases their ability to divide after a heart attack. Murillo showed that inhibiting that protein with a drug also improved the heart’s ability to heal, indicating possible future clinical applications of the drug for treating heart injuries.

Vitello’s presentation, “Wilms Tumor 1 Role in Cardiomyocyte Regeneration,” described network modeling of Wilms Tumor 1 and retinoic acid signaling in cardiomyocyte proliferation. Building on findings from the Wolf lab, she hypothesized that cardiomyocytes that re-express the transcription factor Wilms Tumor 1 are responsive to retinoic acid.

Pavelec was selected to present in the main conference sessions. These are typically populated with talks by faculty, reflecting the strength of her postdoctoral research. Her talk, “Physiological Stress and Cardiomyocyte Cycling Drive Hypertrophic Cardiomyopathy with MYBPC3 truncation mutation,” investigates the genetic origins of hypertrophic cardiomyopathy (HCM), a condition where heart muscles, particularly in the left ventricle, thickens and stiffens, resulting in poor heart function. One gene mutation is responsible for an outsized percentage of cases. Pavelec used CRISPR-based gene editing to create a mouse model with the same genetic profile as a HCM patient at UVA. The model develops symptoms like human patients – increased heart mass, increased wall thickness, and decreased circulation efficiency. Interestingly, these symptoms got worse each time the mice became pregnant. This presents the team with a possible avenue to develop therapeutics for HCM.

Congratulations, Alex, Bryce, Julian, and Katie!

While most associate ultrasound with imaging, Sheybani’s research focuses on the therapeutic uses of ultrasound. FUS tunes sound waves to precisely target tumors. This technique allows the Sheybani lab to directly damage cancerous tissue or stimulate the immune system around it—one of their primary research avenues. Her team aims to understand how FUS can influence immune cells, alter the tumor microenvironment, and in particular, enhance the effectiveness of immunotherapies. Tuning FUS parameters can modulate immune cell signaling, extracellular vesicles, and other components of the tumor microenvironment to make them more susceptible to existing treatments. Thus far, Sheybani’s research has targeted high-risk breast cancers and adult and pediatric brain cancers – with new projects ramping up in ovarian and pancreatic cancers.

The Era of Hope Scholars Award emphasizes patient advocacy, building dialogue between breast cancer survivors and caregivers to demystify the research process, thereby ensuring patient perspectives are actively incorporated into research directions. “This is going to define a new era for our lab because we’re going to start, in partnership with the UVA Comprehensive Cancer Center, a coalition to bring to the table researchers like me, trainees, patient advocates, and other stakeholders from the community to discuss a topic critical to our catchment area – breast cancer. We’re going to build an infrastructure where we can sustainably tear down walls between researchers and patients,” Sheybani explains.

UVA Health was an early leader in focused ultrasound therapies, and this award will further the university’s preeminence in the field. Sheybani, currently the Director of UVA’s Focused Ultrasound Institute, received her initial training in the technique during her PhD training at UVA. “This grant gives us the vote of confidence and resources to put a sincere effort into a goal that I came back to UVA with, which was delivering on advancements in FUS technology for breast cancer,” says Sheybani.