2025 Transformative Neuroscience Pilot Grant Awards
The UVA Brain Institute offers a seed funding program for transformative neuroscience research projects. The purpose of the program is to tackle important questions, promote interdisciplinary collaboration, and perform groundbreaking work that will enhance our research enterprise.
Awarded applications were selected after two rounds of review based on 1) Scientific Merit – Significance, Innovation, Approach, Investigators; 2) Potential for scientific impact and future external funding; and 3) Potential impact of the pilot award on the project and team.
For the first cycle, a total of 23 applications were received. Each written application was initially scored by two or more internal reviewers, and ten finalist teams were invited to pitch their project to a panel of peer reviewers from across the UVA neuroscience community. Both initial scores from written review and pitch scores were considered to determine awardees.
2025 Cycle 1 (Spring) Awardees
Developing a theranostic toolkit to guide and enhance brain tumor-directed CAR T cell therapy with focused ultrasound
Kelsey Kubelick, PhD* – Department of Biomedical Engineering, Daniel Lee, MD – Division of Pediatric Hematology & Oncology, Natasha Sheybani, PhD* – Department of Biomedical Engineering
The last several decades have seen rapid advancement of a powerful new class of immunotherapy - chimeric antigen receptor (CAR) T cell therapy. However, remarkable benefits in other cancers have not extended to patients with brain tumors, highlighting a critical need for “theranostic” (therapeutic + diagnostic) approaches to enhance therapy. We propose a disruptive new strategy to improve CAR T cell therapy in the brain via a unique combination of focused ultrasound (FUS) to potentiate therapy while developing versatile imaging strategies to monitor progress towards personalized-treatment planning.
Engineering 3D Environments to Study Glio-Vascular Interactions
Kyle Lampe, PhD – Department of Chemical Engineering, Lakeshia Taite, PhD – Department of Chemical Engineering
Connections between different types of cells within the brain are vitally important in disease and regeneration. For instance, oligodendrocyte precursor cells (OPCs) migrate along blood vessels before differentiating into myelinating oligodendrocytes. We aim to create a reproducible model system that allows us to study the interactions and signaling events at this OPC-vessel interface that direct critical OPC behaviors which could provide insight into the production and degradation of myelin.
Generative AI Models of Brain MRI for Predicting Alzheimer’s Disease Progression and Risk
Thomas Fletcher, PhD – Department of Electrical & Computer Engineering, Ifrah Zawar, MD* - Department of Neurology
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder, affecting around 6.9 million people in the U.S., and is the leading cause of disability and death in older adults. Identifying mild cognitive impairment (MCI) individuals at risk for progression to AD dementia and those with pre-existing AD at risk of rapid decline is crucial for early intervention and targeted treatments. In this project, we propose to develop a state-of-the-art generative artificial intelligence (AI) model for generating longitudinal predictions of a patient’s cognitive trajectory and risk of neurodegeneration based on brain MRI. The ability to predict patients’ neurodegenerative trajectories will have a significant scientific impact, as it can transform the clinical care of persons with AD.
High-resolution motion-compensated multi-contrast silent MRI for pediatric neuroimaging
Mathews Jacob, PhD – Department of Electrical & Computer Engineering, Kevin Pelphrey, PhD – Department of Neurology
This research aims to develop a quieter, motion-compensated MRI method for imaging infants. It will enhance imaging during sleep and studies on brain responses to social sounds, with the focus on understanding brain developmental issues in autism. The successful completion of this proposal will provide a strong foundation for NIH grants focused on a silent MRI protocol including (a) structural, (b) functional, and (c) diffusion MRI.
Monitoring Cerebral Hemodynamics & Autoregulation in Spreading Depression
Thomas Floyd, MD – Department of Anesthesiology, Andrew Carlson, MD – Department of Neurosurgery
Severe acute neurological injuries, including traumatic head injury, stroke, aneurysm rupture, massive blood loss from injuries, and cardiac arrest all are associated with high levels of mortality, loss of quality of life, and financial burden. Spreading depression (SD), a common but massive abnormality in brain electrical activity, is associated with rapidly evolving brain tissue damage with these injuries and cannot be easily detected by usual diagnostic tools. Herein, we propose a pilot study to test a novel brain device that, when employed alongside encephalography, may enhance the early detection of SD and the associated damaging changes in blood flow (spreading ischemia), potentially allowing for more rapid interventions to improve outcomes.
The Cardiovascular Regulation of Seizures and SUDEP
Ian Wenker, PhD* - Department of Anesthesiology, Brant Isakson, PhD – Department of Molecular Physiology & Biological Physics
Sudden Unexpected Death in Epilepsy (SUDEP) accounts for between 8 and 17% of all epilepsy-related deaths and, although our understanding of SUDEP is rudimentary, there is increasing evidence that respiratory arrest after a convulsive seizure is the primary cause in many cases. In support of this, we have found that seizure-induced apnea that occurs during the tonic phase and failure of postictal breathing recovery produce SUDEP in mouse models. Using our established mouse models of SUDEP, we propose to examine the role of hypotension in facilitating this deadly respiratory arrest.
The role of non-canonical WNT signaling in ALS
Stefanie Redemann, PhD – Department of Molecular Physiology & Biological Physics, Xiaowei Lu, PhD – Department of Cell Biology, Ariel Pani, PhD* - Department of Biology
Amyotrophic Lateral Sclerosis (ALS) is a severe, incurable disease caused by the gradual loss of motor neurons, neuronal cells that control muscle movements, leading to muscle weakness, paralysis and ultimately death. Data using ALS patient cells indicate the dysregulation of a key signaling pathway potentially critical for the correct structure and function of motor neurons. By using advanced genetic tools and imaging techniques in invertebrate and vertebrate model organisms, we aim to understand how dysregulation of this pathway contributes to ALS and potentially identify new targets for treatment.