Seale Innovation Fund

More than eight million cancer patients received radiation therapy in 2018, yet less than half finished a full course due to rejection and gastrointestinal side effects. Robert Gourdie, professor and director of the Fralin Biomedical Research Institute Center for Vascular and Heart Research, is developing an orally administered countermeasure to prevent radiation side effects. Rachel Letteri, assistant professor in UVA’s Department of Chemical Engineering, and her research team will assist Gourdie’s lab by loading milk-derived nano-capsules - purified at large scales for the first time by Gourdie’s laboratory last year – with a peptide currently in Phase III clinical trials that’s been previously shown to reduce radiation burns on skin. Ilektra Athanasiadi, assistant professor of radiation oncology at the Virginia-Maryland College of Veterinary Medicine Animal Cancer Care and Research Center will evaluate the peptide’s effects on weight, activity levels, illness and mortality, as well as gut tissue analysis in mice following radiation therapy. Gourdie is also a professor in the College of Engineering Department of Biomedical Engineering and Mechanics (BEAM).

Nearly 100% of children diagnosed with diffuse intrinsic pontine gliomas, an aggressive form of pediatric brain cancer, die within five years of diagnosis. The treatment-resistant tumors are often inoperable due to their location in the brainstem. Interdisciplinary researchers led by Jennifer Munson, associate professor at the Fralin Biomedical Research Institute, will combine and evaluate focused ultrasound therapy – hypothesized to improve drug delivery across the blood-brain barrier – with sonodynamic therapy, and various cancer drug combinations. Munson is joined by co-investigators Javad Nazarian, head of the DIPG/DMG Center Zurich at University Children’s Hospital in Switzerland and associate professor at George Washington University and Children’s National Hospital; and Eli Vlaisavljevich, assistant professor in BEAM, where Munson is also a faculty member.

Patients with underlying cardiovascular disease are at higher risk of developing cardiac symptoms following COVID-19 infection. Similarly, healthy athletes are also predisposed to cardiac complications, such as viral myocarditis, after testing positive. A research team led by Jamie Smyth, associate professor at the Fralin Biomedical Research Institute, hypothesizes that gene expression in stressed heart muscle cells – due to disease or exercise-related conditioning – may increase the risk of COVID-19 infecting the heart tissue. In 2020, Smyth’s laboratory conducted a study that illuminated how the common cold virus remodels molecular communication structures in the heart leading to arrhythmias. In the new study, Smyth’s team will evaluate how COVID-19 infections alter gene expression, protein distribution, and heartbeat regularity in both normal and hypertrophic, or stressed and enlarged, heart muscles in mice. The study aims to identify molecular changes in the heart and whether preexisting hypertrophy puts some at greater risk of developing severe COVID-19 cardiac symptoms. Smyth is also a faculty member in the College of Science Department of Biological Sciences.

Human milk is one of the best nutritional sources for babies – yet its molecular contents remain largely unknown. Previous research has shown that infants fed exclusively human milk show different developmental trajectories in major white matter tracts in the brain, when compared to formula-fed infants. Brittany Howell, assistant professor at the Fralin Biomedical Research Institute, hypothesizes that nano-capsules composing 20% of human milk are transporting microRNAs to the baby – genetic instructions that may help guide myelination and white matter development postnatally. The researchers want to begin evaluating which specific microRNAs in human milk are linked with certain features of neurodevelopment. Howell is also a faculty member in the College of Liberal Arts and Human Sciences' Department of Human Development and Family Science.  She is joined by co-investigators Yassine Sassi, assistant professor at the Fralin Biomedical Research Institute and in the Virginia-Maryland College of Veterinary Medicine Department of Biomedical Sciences and Pathobiology (DBSP), and Paul Morton, assistant professor in DBSP.

In 2016, Read Montague, professor and director of the Fralin Biomedical Research Institute Center for Human Neuroscience Research, and his research team made groundbreaking, first-ever measurements of dopamine in a conscious human subject. The tiny carbon fiber probes, temporarily implanted in the brain during an awake neurosurgery procedure, provided the researchers with real-time measurements of both dopamine and serotonin in 2020. Now, Montague’s team is adding statistical learning procedures to correlate brain chemistry with rapid pupil dilation changes to detect sub-second fluctuations in a third neurotransmitter: norepinephrine. These first-of-their-kind measurements will reveal relative roles of dopamine and norepinephrine, revealing further insight into the chemical interactions underlying human cognition. Montague is also a professor in the College of Science Department of Physics.

Ultra-processed, calorically dense foods are linked with increased risk of developing obesity, type 2 diabetes, heart disease, and cancer – yet these foods continue to be overconsumed. Alexandra DiFeliceantonio, assistant professor and associate director of the Fralin Biomedical Research Institute’s Center for Health Behaviors Research, will relate metabolic, neural, and behavioral data to understand how our brains process nutrient availability and food preference. The project uses the institute’s new whole-room calorimeter facility – among the first of its kind - to measure changes in metabolic rates. DiFeliceantonio also is a faculty member in the College of Agriculture and Life Sciences Department of Human Nutrition, Foods, and Exercise.

In light of the opioid epidemic, alternative, non-addictive treatments for pain are critically needed. A neuroscience team led by Wynn Legon, assistant professor at the Fralin Biomedical Research Institute, will advance and optimize low-intensity focused ultrasound to non-invasively control chronic pain. The researchers – using the institute’s new MR-guided focused ultrasound facility – will target different areas in the insula, a brain region that prior research suggests plays a role in processing pain perception in humans. Legon also is a faculty member in the College of Science’s School of Neuroscience.