Seed Funding

The UVA Brain Institute has offered seed funding for six key cross-grounds collaborative research projects in development-related work, with the purpose of bringing neuroscience investigators together to tackle important questions and perform transformative work that will differentiate our research enterprise. These initiatives require diverse expertise, and involve investigative teams from a variety of disciplines and/or Schools across grounds. 

sanchita

Sanchita Bhatnagar, PhD

A novel, effective microRNA-based gene therapy approach for Rett Syndrome

Rett Syndrome (RTT)  is the second most common cause of severe intellectual disability after Down Syndrome and has no cure. It is caused by a mutation of the MECP2 gene, which is located on the X chromosome. Therefore, if one of the X chromosomes is inactivated by epigenetic silencing, the MECP2 gene is also inactivated. These researchers are trying to understand if reactivating the MECP2 gene on an inactivated X chromosome can cure Rett Syndrome. They are trying to do this by preventing molecules that control the MECP2 gene from working normally in mice, and seeing if this will allow MECP2 to function normally through the correction of Rett Syndrome-like behavior.

Meghan Puglia, PhD

Brain Signal Entropy and Oxytocin Receptor Epigenetics: Neurobiological Markers of Social Developmental Variability

Brain signal entropy, which measures constantly changing differences in brain signals, has been linked to cognition. With respect to cognitive performance, increased entropy is associated with more stable behavior responses. Moreover, in the context of cognitive development, young adults tend to have greater brain signal entropy than pre-adolescents. Perceiving social information is critical for adaptive learning and behavior, but different individuals display varying levels of perceptual biases. In extreme cases, these differences in perceptual biases may be linked to autism. This study aims to link social behavioral outcomes to early-life epigenetic changes in Oxytocin and brain signal entropy during social perception. Understanding the neurobiology of social development has potential for improving health outcomes.

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grossman

Tobias Grossman, PhD

Investigating the role of the microbiome in early brain and behavioral development

Bacteria in the gut are not only important for digestion, but also affect brain function and mental health through the microbiota-gut-brain axis, but how it does so is not well understood. Too much or too little bacteria in the gut is linked to negative affect and internalizing disorders like anxiety and depression, especially bias towards threatening stimuli (threat bias), which is also related to dysregulation in the prefrontal cortex part of the brain. This study aims to understand the role of the microbiome gut bacteria’s role in threat bias and how it impacts subsequent behavior. Understanding factors of well being, healthy brain function, and emotion regulation can help guide early human development.

Jessica Connelly, PhD

Epigenetic Consequences of Maternal Oxytocin Treatment in Offspring

Synthetic oxytocin, a hormone, has been used to induce labor. In prairie voles, administering synthetic oxytocin to pregnant mothers encourages them to spend more time with each other and their offspring. In humans and prairie voles, the receptor for oxytocin, is under epigenetic control by means of chemical changes called methylation (OXTRm). OXTRm, which is influenced by early life experience, is associated with autism and social perception. This study aims to understand the ways that oxytocin treatment influences behavioral changes. The researchers will do this by studying another epigenetic change called hydroxymethylation, which causes more genes to be expressed. They will also investigate the changes in histones (H3K4me3 and H3K27me3) at the receptor for oxytocin. Histones are proteins that DNA wraps around. In looking at these different epigenetic processes, the understanding of administering oxytocin as a birth intervention in humans will be furthered.

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Dutta

Aninya Dutta, MD PhD

Short Non-coding RNAs in Autism-Related Disorders

Epigenetics is a field of research that aims to understand how the environment can influence gene expression. Past studies have suggested that environmental factors, such as diet and stress, can affect the chemical marks accumulating on DNA. Some of these chemical marks include short non-coding RNAs, which, if accumulated in the parent, can directly lead to behavioral changes in offspring. Previous analysis of these short non-coding RNA chemical marks in autistic brains have exhibited microRNA dysregulation, as well as suggesting that changes in parental microRNAs can increase the odds of having a child with autism. This study is attempting to identify the specific non-coding RNA changes related to autism, based on the maternal immune activation (MIA) model of autism spectrum disorder. Long term, these researchers are interested in understanding how short non-coding RNAs are regulated and related to neurodevelopmental disorders.

Sarah Miller, DO

NICU Predictive Analytics for Cognitive and Behavioral Disabilities

With preterm infants having over a 10-fold higher rate of intellectual disability, autism spectrum disorder, and executive function compared to full term infants, the prediction of such conditions during or soon after the NICU stay may improve their outcomes. The autonomic nervous system, which controls vital signs such as heart rate, respiratory rate, and blood pressure, is associated with parts of the brain related to mood, memory, and emotion cognition. The NICU at UVA continuously monitors its patients’ vital signs, and follows high risk infants until they are 2 years of age in the follow-up clinic. These researchers are interested in analyzing heart rate and other vital signs, which reflect central autonomic nervous system function, to predict longer term neurodevelopmental outcomes (ASD, ID, ADHD) toward improving early neonatal interventions and outcomes.

 

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morris

Jamie Morris, PhD

Individual Variability in the Oxytocinergic System and the Development of Human Sociality

Oxytocin is a biological hormone that serves as a marker for social behavior, such as understanding emotions and expressing empathy. A process called methylation can chemically mark the receptor for Oxytocin (called OXTRm), which is associated with autism and a variety of brain activity in adult social perception. Oxytocin levels may influence the methylation of its receptor, and prior work has shown that lower levels of such methylation is associated with higher social sensitivity. In this study, researchers are trying to establish a clear relationship between the OXTRm and brain patterns of emotion comprehension and social cognition in children aged 5-9 and generate their social cognitive and prosocial trajectories related to OXTRm. Overall, understanding the stability of OXTRm during development will be of great value.