2024 Transformative Neuroscience Pilot Grant Awards
Cycle 1 Awardees announced!
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.
2024 Cycle 1 Awardees
A Novel Rewarding Food Consumption Circuitry Targeted by the Next Generation Weight-Loss Drugs
Ali Güler, PhD - Department of Biology, John Campbell, PhD - Department of Biology
This proposal presents a novel approach to mapping the neural circuits involved in overeating and obesity revealed by the glucagon-like peptide-1 receptor (GLP1R) agonists. Hailed as the "Breakthrough of the Year'' by Science magazine, these agents, the likes of Ozempic and Mounjaro, are revolutionizing the management of metabolic disorders. Our aim is to deepen the understanding of the neuronal circuits that curb hedonic eating (eating beyond the body's energy needs) and use this insight to provide platforms to refine weight loss medications.
Brain microvascular pericyte pathology linking Alzheimer's Disease and Type II Diabetes
Shayn Peirce-Cottler, PhD - Department of Biomedical Engineering, Ukpong Eyo, PhD - Department of Neuroscience
Type II Diabetes is a major risk factor for Alzheimer’s Disease, and we hypothesize that these two diseases are connected through the smallest blood vessels in the brain, the capillaries. Our study will test the hypothesis that both diseases fundamentally disrupt the connections between the cells that form the brain capillaries, causing leaky capillaries and dysregulated blood flow, both of which contribute to impaired brain function. We will study how cell connections in capillaries become disrupted over time and identify strategies to prevent this from happening in Alzheimer’s Disease and Type II Diabetes and when both diseases are present.
Glial-regulated mechanisms of aberrant axonal outgrowth in Alzheimer's Disease across species
Jaeda Coutinho-Budd, PhD - Department of Neuroscience, Elise Cope, PhD - Department of Neuroscience
Alzheimer’s Disease (AD) is a neurodegenerative disease that occurs in the aging population, yet many genes with prominent roles in development are upregulated in the AD brain. Aberrant axonal growth near amyloid plaques was first reported decades ago, and numerous axon guidance and growth factors have been found to be dysregulated in AD, but the extent of how and where these molecules act in AD remains ambiguous to this day. We propose to develop new in vivo Drosophila genetic tools to test mechanistic questions quickly and translate these findings directly into a novel mammalian model to explore the molecular underpinnings of this understudied, yet important phenomenon in AD.
Toward Non-Invasive Gene Therapy and Liquid Biopsy for Childhood Neurodevelopmental Disorders with Transcranial Focused Ultrasound
Sameer Bajikar, PhD - Departments of Cell Biology and Biomedical Engineering, Natasha Sheybani, PhD - Department of Biomedical Engineering
In this Brain Institute Transformative Neuroscience grant, we will explore the use of focused ultrasound (FUS) for localized blood brain barrier opening to non-invasively deliver gene viral therapy to models of Rett syndrome, a severe childhood neurological disorder. To date, no studies have leveraged FUS in Rett syndrome despite an urgent clinical need for less invasive treatments, gene therapy dose de-escalation, and improved biomarkers. We will assess the use of FUS to (1) deliver gene therapy in a titratable fashion and (2) amplify peripheral bioavailability of CNS-derived biomarkers that can inform risks of overtreatment in gene therapy strategies for Rett.
Investigating anxiety-related variability in brain structure-function coupling during adolescence
Stefanie Sequeira, PhD - Department of Psychology, Aiying Zhang, PhD - School of Data Science
Anxiety disorders are the most common mental health disorders affecting children and teens, and up to half of youth who receive treatment for an anxiety disorder do not fully benefit from treatment. To improve treatment, we must deepen our understanding of how the diverse symptoms and behaviors that characterize different anxiety disorders in youth develop. Recent advancements in brain imaging techniques offer promising avenues for advancing this understanding. Led by two new faculty members in Psychology and Data Science at UVA, this project uses innovative methods of combining brain data and clinical and behavioral assessments to examine how brain structure and function is linked to the development of different anxiety-related symptoms and behaviors throughout adolescence in over 10,000 U.S. youth recruited for the Adolescent Brain and Cognitive Development Study. This project will help us better understand the complexity of youth anxiety, with the potential to influence how we think about and design treatments for anxiety in children and teens.
Inceptor, brain insulin resistance and postpartum depression
Heather Ferris, MD, PhD - Division of Endocrinology and Metabolism, Jennifer Payne, MD - Department of Psychiatry and Neurobehavioral Sciences
Post-partum depression is a potentially life-threatening condition, however the causes are poorly understood. Both abnormal estrogen sensitivity and insulin resistance are risk factors for post-partum depression. We will determine if a protein called Inceptor, which is estrogen-regulated and a driver of insulin resistance, is the molecular link between insulin resistance and post-partum depression.
Developing and Validating a Remotely Administered, Digital, Gait-Based Marker to Predict Future Cognitive Decline in Patients with Pediatric-Onset Multiple Sclerosis
Nick Brenton, MD - Department of Neurology, Laurie Brenner, PhD - Department of Neurology, Laura Barnes, PhD - Department of Systems and Information Engineering
Pediatric-onset multiple sclerosis (POMS) patients are at high risk for cognitive impairment; however, there are no current measures to predict those at highest risk, thus limiting our ability to identify, implement, and study interventions that could prevent cognitive decline. In our preliminary work, we show that six-minute walk gait speed trajectories (6MWGST) near the time of diagnosis can predict those POMS patients at risk for future cognitive decline. Our current proposal seeks to a) validate the 6MWGST as a prediction tool for future cognitive decline in POMS by confirming our preliminary findings using a detailed assessment of neurocognitive function and b) develop this outcome for remote administration to facilitate future multicenter implementation and inclusion of rural/underserved patients.
This page will be updated as additional pilot grants are awarded.