Broadly, Mills seeks to understand how microglia, the primary immune cells in the human nervous system, regulate blood flow through the brain’s smallest blood vessels. In studies of the human genome, many of the genes that indicate risk for Alzheimer’s Disease (AD) are found in microglia, suggesting that these cells play a role in the disease. One of the key indicators of AD is reduce blood flow through the brain, the earliest sign a person is developing the condition. As the disease progresses, blood flow to the brain can drop by over 25%, effectively starving neural cells. Microglia, as immune cells, are responsible for controlling brain inflammation, which in turn affects cerebral blood flow. Taken together, these factors all suggest microglia could be valuable drug targets for improving AD treatments.

An influential work in the Alzheimer’s field, known as the Rotterdam Study, reviewed 11,475 patient records and found that early and prolonged treatment with non-steroidal anti-inflammatory drugs protected against AD. These drugs are common, including pain medications like aspirin and ibuprofen, but the reason they help Alzheimer’s patients is unclear. They are also imperfect treatments. “These drugs have severe gastrointestinal toxicity, so if we can learn what specifically we want to target, we can think about a more precise method to make a better, safer drug,” explained Mills. Through advanced genetic and imaging methods, Mills will visualize the flow of blood through mice and measure how age and pain medication affect it. If pain medication offers no benefit beyond genetic perturbation, then a more precise target can be inferred, thereby aiding future therapeutic development. 

A former member of the cardiovascular training program at the CVRC, Mills attributes part of his success to the grant brewing sessions and mentorship he was able to access through the program. The K99 will assist his further development by providing access to training and materials that will make him more competitive for independent research faculty positions in the future. “I’ll be able to do experiments that we haven’t been able to do before,” Mills said. “My dream is to someday make cost-effective therapeutics for Alzheimer’s Disease.”

Polizio, mentored by CVRC resident member Ken Walsh, PhD, is an expert in age-related clonal cell hematopoiesis. As we age, our cells acquire a variety of mutations. These mutations can propagate over time, with mutated cells eventually able to outnumber the nonmutated. These mutations were previously considered harmless, but Dr. Polizio and Dr. Walsh have shown that clonal cell hematopoiesis has health consequences, particularly by promoting “inflammaging,” long-term, low-level inflammation that prematurely ages tissues and organs. Polizio has shown that in cases of renal cell carcinoma, the most common form of kidney cancer, inflammaging and clonal cell hematopoiesis can exacerbate the side effects of the most common chemotherapy treatments. In fact, these therapies may actually accelerate the mutation accumulation process. The research that won Polizio entrance to the Butler-Williams Scholars Program proposes to explore these effects and identify potential treatments.

“It’s an honor for me to meet with the program officers, directors, and scientific colleagues from around the nation,” says Polizio.

Dr. McKee, mentored by CIC Co-Director Coleen McNamara, MD, is deeply involved in community engagement efforts both within UVA and beyond. She received her medical training at the University of Otago in New Zealand before pursuing a master’s degree in Immunology and Inflammatory Disease at the University of Glasgow, Scotland. While presenting to the approximately 40 high schoolers attending her talk, she used her experience in both clinical and research settings to help delineate the two perspectives. “Imagine a cliff,” Dr. McKee explained. “Clinical medicine is like an ambulance that treats people who fall off the edge. Research science tries to build a fence to stop people from falling in the first place, and there are pros and cons to each approach.” She also described her current research and the importance of being an advocate for science in a national climate increasingly skeptical of research.

Speaking at Monticello High School is Dr. McKee’s latest community engagement effort. She has also volunteered at events that brought middle schoolers to Grounds, UVA’s Discover Medicine program, and Charlottesville’s local Big Brothers Big Sisters chapter. Community service is one of Dr. McKee’s core values, having volunteered in international medical efforts and local programs throughout her professional and personal life.

Her efforts to bring UVA and the Charlottesville community together are already building new bridges. Dr. McKee’s Discover Medicine mentee attended her talk at Monticello High School. Another student who attended that talk subsequently sought out a clinical research rotation and will work at iPRIME this summer.

Dr. Abbate, for his part, has a long history of community outreach. Like Dr. McKee, he spoke about the career that brought him to UVA: an MD/PhD from the Campus Bio Medico University of Rome, Italy, a fellowship at the Universita Cattolica del Sacro Cuore in Milan, Italy, and a residency at Virginia Commonwealth University. He focused, however, on trying to excite the next generation to pursue science. “When I was a young student, people inspired me. Now, my job is to return that inspiration to the community,” Dr. Abbate said. He and the highschoolers discussed a variety of topics, ranging from practical concerns like how long an MD/PhD takes and his research projects to wider questions, like what motivates research and Dr. Abbate’s long-term goals. “It was a very rewarding experience—the students were very excited to learn about careers in science,” he recalled.

Community outreach and engagement is a core value of the CVRC and its researchers. Students and faculty interested in additional outreach opportunities should contact Dr. Christos Baryiames.

Owens gave a broad overview of the current research avenues in his research group, which is largely focused on understanding atherosclerosis. Atherosclerosis is a condition where fatty deposits accumulate in the blood vessels. The body naturally forms a fibrous cap over these deposits, but the thickness of that cap can vary. A thin cap is liable to break, releasing the fats and dying cells into the bloodstream, causing a heart attack or stroke. A thick cap is much more stable. Owens and his team are interested in understanding why these cap thicknesses vary and how controlling inflammation can contribute to better patient outcomes.

Owens’ talk was attended by the UVA cardiovascular community, including 29 Owens Lab members, past and present. His children and grandchildren also attended. “It was a privilege to hear this lecture from someone whose career has so profoundly shaped the field and this institution,” says Isakson. Owens was presented with a plaque and Jefferson Cup in thanks for his lecture and service to the community.

Owens (right) receives a plaque and Jefferson Cup from Isakson (left).

Together, the three researchers will identify correlations between LOY and HFpEF severity, LOY-related changes at the cellular level, and whether mouse models can inform our understanding of the disease. Specifically, the team will investigate whether LOY increases the prevalence of fibrosis, the formation of scar tissue, in the heart. “The work will merge molecular biology and clinical cardiology, particularly cardiac MRI,” Walsh explains. The Walsh lab will provide expertise in LOY and molecular biology methods. Dr. Patel’s research specialization is in cardiac MRI, and Dr. Abuannadi is an expert in heart failure. Together, the trio hopes to identify the sex-specific mechanisms giving rise to HFpEF. Understanding these mechanisms will facilitate future work to develop treatments for HFpEF in men and women.

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.

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.