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.
A total of 23 applications (first cycle) and 30 applications (second cycle) were received. Each written application was initially scored by two or more internal reviewers, and 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 2 (Fall) Awardees
Vital CRISPR/Cas9 Screening Of Metabolic Pathway Genes In Pediatric Glioma Associated Macrophages
James Ross, PhD* – Department of Neuroscience
Kelsey Voss, PhD* – Department of Pharmacology
Pediatric high-grade gliomas are responsible for the most cancer-related deaths in children, have no effective therapies, and are characterized by an abundance of immunosuppressive macrophages with distinct metabolic programming. Our project aims to perform unbiased CRISPR/Cas9 screening and utilize immune competent mouse models of glioma to identify the vital metabolic genes enabling these macrophages to survive, promote immune suppression, and drive tumor progression. This research could reveal novel treatment strategies to reprogram the tumor microenvironment and improve survival for children with brain tumors, and inform new drug targets for other neuroinflammatory diseases marked by macrophage dysfunction as well.
Enhancing Participation and Retention in Dementia Research: Reducing Fatigue and Promoting Cognitive Autonomy
Meghan Mattos, PhD – Department of Nursing Research
Wen You, PhD – Department of Public Health Sciences
The purpose of this study is to examine the effect of mental fatigue on research study participation and engagement among older adults with mild cognitive concerns participating in Alzheimer’s disease (AD) research. Using data from a national, Internet-based trial (SHUTi MIND), we will apply machine learning techniques to characterize fatigue-related patterns of disengagement and test whether perceived autonomy mediates this effect. Findings will inform the design of adaptive, participant-centered digital reminders to reduce burden and sustain engagement in AD prevention studies.
Sleeping Beauty: Sleep, Blood Clearance, and Brain Health after Intracranial Bleeding
Jenna Leclerc, MD, PhD* – Department of Anesthesiology
Tyler Johnson, MD* – Department of Anesthesiology
Sleep is vital to all living organism’s health, as sleep deprivation eventually leads to death; yet despite the clear biological necessity of sleep, exactly how sleep exerts its effects on the body remains a mystery under both normal physiologic and pathologic states. We aim to show that sleep disturbances after intracranial bleeding lead to worse outcomes and secondarily will test whether augmentation of sleep via a highly clinically relevant paradigm improves outcomes. We will additionally test whether these effects are through modulation of blood clearance via a newly identified brain fluid flow pathway in order to start addressing treatment strategies for this major public health problem that currently has no effective treatments.
Integrated PET/MRI Performance Evaluation with RF Coil Optimization: NEMA NU 2 Phantom Testing of a Human-Sized PET Insert in the Siemens 3T MRI
Stuart Berr, PhD – Department of Radiology & Medical Imaging
Joseph Rispoli, PhD – Department of Radiology & Medical Imaging
This project transform UVA's joint PET/MRI research program. For the first time, we will be able to fully characterize the performance of our NIH-developed human-sized PET insert in a 3T MRI environment using standardized methods, while also addressing the critical engineering challenge of RF coil integration. By providing critical preliminary data, this project will accelerate UVA’s ability to compete nationally for high-impact PET/MRI neuroscience research funding.
Endosomal membrane traffic – a novel node for epilepsy
Bettina Winckler, PhD – Department of Cell Biology
Manoj Patel, PhD – Department of Anesthesiology
Epilepsy is a common human condition that can be caused by gene mutations in pathways controlling excitability, such as mutations in critical ion channels and neurotransmitter receptors as well as BDNF receptor. The significance of this project lies in the potential of establishing endolysosomal trafficking as a unifying causative pathway that controls surface levels of many critical receptors that can drive neuronal hyperexcitability. The premise for this project is our surprising observation that loss of RAB7A, a key regulator of endosomal sorting to lysosomes causes epilepsy and early deaths suggesting the hypothesis that imbalance in endosomal traffic caused by RAB7A loss constitutes a new node underlying seizure susceptibility.
A Focused Ultrasound Platform to Treat Vascular Dementia
Joshua Wythe, PhD – Departments of Cell Biology and Neuroscience
Richard Price, PhD – Department of Biomedical Engineering
Cerebral small vessel disease, of which the most common hereditary form is Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), is a major cause of stroke and vascular dementia, yet there are no effective treatments. Transient focused ultrasound-mediated disruption of the blood-brain barrier (BBB) is rapidly advancing through clinical trials as a means for targeted drug delivery to the brain for several indications. This pilot project will test whether focused ultrasound has the potential for safe and effective trans-BBB delivery of model drugs and gene therapies in mice which develop CADASIL through a mutation in the Notch3 gene.
Poly-Substance Use Disorder: Feasibility of Recruitment, Retention, and Development of a Control Neuroimaging Database
James Mahoney, PhD – Department of Psychiatry & Neurobehavioral Sciences
Daisy Thompson-Lake, PhD* – Department of Psychiatry & Neurobehavioral Sciences
Poly-substance use disorder (poly-SUD) remains a major public health crisis in Virginia and suboptimal engagement in treatment affects both clinical outcomes and interpretation of research findings. Additionally, there is no standardized set of brain images and behavioral/cognitive data for poly-SUD to serve as a control comparison (i.e., standard of care) for understanding how new treatments may alter brain circuitry and behavior. This pilot project addresses these issues by engaging local treatment sites to recruit individuals with poly-SUD, assess retention over a follow-up period, and generate the first UVA MRI and behavioral dataset of a poly-SUD population to better understand the impact of poly-SUD, and serve as a comparison with new treatments under investigation.
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.
*Indicates early-career researcher