Seale Innovation Fund

Improving Patient Outcomes After Heart Surgery

Scott Johnstone

Restoring blood flow to the heart surgically can be complicated by smooth muscle cells in the blood vessel wall dividing continuously afterward, eventually blocking blood flow again. The Johnstone lab has developed peptides that can block proteins that promote cell division, but peptides are poor agents for therapeutics. This research will design and test novel nanobodies, based on those peptides, that will be engineered to limit cell division. These therapeutic agents will act as a prototype for translational research aimed at improving patients’ lives after surgery.

Title: Identification of Cell-Permeable Nanobodies to Reduce Smooth Muscle Proliferation

Exploring Novel Treatments for Glioblastoma, Other Cancers

Samy Y. Lamouille

Glioblastoma cancer stem cells are resistant to radiation and chemotherapy. Failure to significantly eradicate these cells results in recurrence, making glioblastoma one of the most lethal diseases, with an average patient survival of 15 months. New treatment options are critically needed for this devastating disease. Lamouille will employ cutting edge molecular and microscopy techniques and clinically relevant models in vitro and in vivo to test a novel therapeutic approach specifically eradicating cancer stem cells. Because cancer stem cells are not unique to glioblastoma, this approach has broad implications in treating other types of cancer and preventing disease progression.

Title: Viral Vector-mediated Expression of a Therapeutic Peptide to Ablate Glioblastoma Cancer Stem Cells
Co-Investigator: James Weger-Lucarelli, Virginia-Maryland College of Veterinary Medicine

Investigating Stem Cell Dysregulation in Early Brain Development

Thomas Maynard

During development of the outer layer of tissue in the human brain, stem cells proliferate and diversify to eventually form the neural circuits that underlie cognitive behaviors. There’s a careful balance at play, and regulation of that balance is a target for better understanding a range of developmental disorders, including autism spectrum disorder and schizophrenia. This research investigates the connection between neural stem cell dysregulation and clinically defined neurodevelopmental disorders.

Title: A New Approach to Identify Cortical Stem Cell Pathology in Neurodevelopmental Disorders
Co-Investigator:  Anthony LaMantia, Fralin Biomedical Research Institute at VTC

Changing How We Study the Rhythms of Life

Steve Poelzing

Rhythmic electrical activity in excitable cells is necessary for life as we know it; some spontaneously excite on their own. Scientific understanding of this activity arises from studying what happens inside isolated cells, which has prevented the development of effective therapies to treat abnormal electrical activity in the brain (epilepsy), the heart (sudden cardiac death), the gut (intestinal pseudo-obstruction), and the uterus (premature birth). This research seeks to determine whether the outside of the cell, rather than the inside, can provide a more complete understanding of the rhythms of life and point toward new therapies.

Title: An Outside-In View on Cellular Automaticity: Changing How We Study the Rhythms of Life
Co-Investigator:  Gregory Hoeker, Sharon Swanger, Fralin Biomedical Research Institute at VTC

Developing a Better Understanding of Stress, Inflammation, and Chronic Pain

Sora Shin

Numerous studies have shown that stress, including early life trauma in the form of child abuse or neglect, induces long-lasting changes in the immune system. Specifically, researchers are interested in stress-induced altered sensitivity to pain, as many people who suffer from chronic pain also experienced early life trauma. This research seeks to better understand the neural circuits and connections between trauma, abuse and changes in an individual’s pain response and is a novel exploration of the impact of specific neurons on inflammation and chronic pain.

Title: Role of the Midline Thalamic Network in Top-Down Control Of Stress-Induced Hyperalgesia

Novel Therapies to Treat Heart Failure in Patients with Type 2 Diabetes

Junco Warren

Heart failure is a leading cause of death and hospitalization in the United States, and diabetes is a major risk factor. Patients with type 2 diabetes often suffer from heart failure in which the left ventricle is too stiff to function properly. While the number of patients with the diagnosis has increased, the treatment of those patients has been challenging, in part due to the complexity of the way the disease develops. Warren's work seeks novel therapies to treat heart failure in patients with type 2 diabetes.

Title: Novel Therapeutic Approach to Treat Heart Failure Patients with Type 2 Diabetes

Taking Aim at Deadly Pediatric Brain Cancer

Jia-Ray Yu

Diffuse midline glioma is  the  most  aggressive  form  of  pediatric  brain  cancer, with  no  effective therapy. The five-year survival rate is less than 1 percent. Development of targeted therapies is a challenge because the condition’s mutations are unsuitable for drug therapy. Researchers have identified two enzymes that show promise as targets for combination therapies, however. The objective of this research is to investigate the biology of those enzymes and uncover potential targets for combination therapies to treat this uncurable disease.

Title: Synthetic Lethality Screening for Druggable Factors that Amplify a Cancer Dependency in Diffuse Midline Glioma
Co-Investigator:  Wei Li, Javad Nazarian, Children’s National Research Institute

Reducing Radiation Therapy Side Effects

Robert Gourdie

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).

Improving Brain Cancer Drug Delivery and Treatment

Jennifer Munson

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).

Heart Health and COVID-19 Complications

James Smyth

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.

Milk's Role in White Matter Brain Development

Brittany Howell

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.

Next-Generation Neurotransmitter Prediction Systems

Read Montague

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.

Processed Food and Preference

Alexandra DiFeliceantonio

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.

Treating Chronic Pain with Focused Ultrasound

Wynn Legon

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.