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One of the most prominent surveillance systems in the body that protects against mistakes in gene expression that lead to disease, NMD is a complex pathway that is at the heart of many of the collaborations between Maquat and other University of Rochester scientists. Together, with funding from the National Institutes of Health (NIH) and the FRAXA Research Foundation, they aim to gain a deeper understanding of the sophisticated mechanisms related to NMD that will contribute to developing new drug therapies for genetic disorders such as fragile X syndrome, cystic fibrosis, and hundreds of others.
The Prschel lab makes and differentiates neural stem cells that mimic fragile X syndrome, allowing his team to test hypotheses and understand how different therapies impact cell biology and function. He and Tatsuaki Kurosaki, Ph.D., research assistant professor in the Maquat lab, used these neural stem cells to understand the relationship between FMRP and NMD. They discovered that NMD controls the amounts of messenger RNAs deriving from a wide range of genes throughout the brain, including genes that govern motor control and cognitive processes related to attention, learning, and language. They also found that when FMRP is absent from cells, as it is in people with fragile X syndrome, NMD shifts into overdrive.
This work was part of a 2021 study published in Nature Cell Biology led by Maquat that revealed that tamping down NMD with small molecule inhibitors restored a large proportion of neurological functions in these cells.
Most recently, Prschel co-authored research published in Molecular Cell led by Maquat and co-authored by Hana Cho, Ph.D., and Elizabeth Abshire, Ph.D., of her lab. The study highlighted a complex molecular dance between NMD and the enzyme AKT, which plays a key role in cell growth and survival. Both AKT and NMD are overactive in fragile X. Using neural stem cells that lack the FMRP protein, they tested a drug called Afuresertib, which inhibits AKT. They discovered that blocking AKT in the fragile X cells decreased its activity and decreased NMD. These cells then acted more like typical, non-disease cells.
As a neurotologist (subspecialist of Otolaryngology), Hitomi Sakano, M.D., Ph.D., spends time in the clinic with patients with hearing issues or hearing loss. In the lab, she aims to understand how the brain adapts to sound information.
Her work with fragile X syndrome began as a resident at the University of Washington when she took interest in FMRP, which is highly expressed in the auditory brainstem nuclei of a typical brain and is the same protein missing in fragile X patients. When Sakano came to the Medical Center in 2018, she brought the fragile X mouse model to study this and joined the Center for RNA Biology.
normal processing of auditory information. If true, there may be therapeutic targets for symptoms like auditory hypersensitivity in fragile X. Funding from the Schmitt Program in Integrative Neuroscience (SPIN) through the Del Monte Institute for Neuroscience Pilot Program and a NIH Research Career Development Award for clinician-scientists are supporting her research, which involves investigating the gene expression abnormalities in the auditory brainstem of the fragile X mouse model that might explain the auditory hypersensitivity in these mice. To date, she has found some interesting RNAs that encode synaptic proteins. These findings open up the possibility of targeting these genes for the treatment of hyperacusis.
In the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory, research assistant professor Tufikameni Brima, Ph.D., is aiming to use electroencephalography (EEG) and event-related potentials (ERP) to better understand how the brains of patients with fragile X respond to various stimuli. This work has the potential to build upon the ongoing molecular research being conducted by Telias and others.
The study now out in NeuroImage, describes how listening and watching a narrator tell a story activates an extensive network of brain regions involved in sensory processing, multisensory integration, and cognitive functions associated with the comprehension of the story content. Understanding the involvement of this larger network has the potential to give researchers new ways to investigate neurodevelopmental disorders.
Researchers designed this experiment with children in mind, according to the investigators who have already begun working with both children and adults on the autism spectrum in an effort to gain insight into how their ability to process audiovisual speech develops over time.
University of Rochester researchers have been at the forefront of efforts to understand how blows to the head impact the brain, including how concussions change brain structure . Now researchers at the Del Monte Institute for Neuroscience have found that kids who experience a traumatic brain injury (TBI), even a mild one, have more emotional and behavioral problems than kids who do not.
Researchers used MRI and behavioral data collected from thousands of children who participated in the Adolescence Brain Cognitive Development (ABCD) Study. They revealed children with a mild TBI experienced a 15-percent increased risk of an emotional or behavioral problem. The risk was the highest in children around ten years old. Researchers found that children who had a significant hit to the head but did not meet diagnostic criteria for a mild TBI also had an increased risk of these behavioral and emotional problems.
The University of Rochester Medical Center is one of 21 research sites collecting data for the National Institutes of Health ABCD Study. Since 2017, 340 children from the greater Rochester area have been part of the 10-year study that is following 11,750 children through early adulthood. It looks at how biological development, behaviors, and experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, and overall health.
Additional co-authors include Zachary Christensen, John J. Foxe, Ph.D., Laura Ziemer, and Paige Nicklas, all members of the Frederick J. and Marion A Schindler Cognitive Neurophysiology Lab that is part of the Del Monte Institute for Neuroscience at the University of Rochester. The research was supported by the National Institute on Drug Abuse, and the UR Intellectual and Developmental Disabilities Research Center.
The CAREER awards recognize role models in research, education and provides recipients five years of funding to help lay the foundation for their future research. Ross's research will explain how our brain stems help us listen and converse in noisy settings.
Using the Mobile Brain/Body Imaging system, or MoBI, researchers monitored the brain activity, kinematics and behavior of 26 healthy 18 to 30-year-olds as they looked at a series of images, either while sitting on a chair or walking on a treadmill. Participants were instructed to click a button each time the image changed. If the same image appeared back-to-back participants were asked to not click.
In a new paper published in the journal eLife, researchers at the University of Rochester, including Greg DeAngelis, the George Eastman Professor of Brain and Cognitive Sciences, and his colleagues at Sungkyunkwan University and New York University, describe a novel neural mechanism involved in causal inference that helps the brain detect object motion during self-motion.
Searle Scholars Program names 15 scientists as Searle Scholars for 2022Members of the new class of Searle Scholars pursue ground-breaking research in chemistry and the biomedical sciences. Each receives an award of $300,000 in flexible funding to support his, her, or their work over the next three years.
With $15.6 million from the National Institute of Mental Health, scientists will investigate the brain networks central to obsessive compulsive disorder in order to guide the development of effective treatments. A team of scientists from across the country will use a $15.6 million award from the National Institute of Mental Health to investigate the brain networks central to obsessive compulsive disorder (OCD). The work will build on more than 15 years of research by lead investigator Suzanne N. Haber, Ph.D. and collaborators to understand the underlying biology of the disease and guide the development of effective treatments.
In 2020, the Neuroscience Diversity Commission (NDC) was formed following a letter penned by the director of the Del Monte Institute, John Foxe, Ph.D., in response to the death of George Floyd.
The University of Rochester Medical Center is one of 21 research sites across the country collecting data for the National Institutes of Health ABCD Study. Since 2017, 340 children from the greater Rochester area have been participating in the 10-year study. In all, the study is following 11,750 children through early adulthood looking at how biological development, behaviors, and experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, and overall health.
In previous research, fMRI was used to scan the brains of participants as they listened to different types of speech and music. Norman-Haignere combined the fMRI data from this prior study in order to map the locations of song-selective neural populations, which were identified in their new ECoG study.
The associate professor of Neuroscience and his Del Monte Institute colleagues published a study in NeuroImage that provides evidence of how the brain takes on multiple tasks without sacrificing how either activity is accomplished. "Looking at these findings to understand how a young, healthy brain is able to switch tasks will give us better insight to what's going awry in a brain with a neurodegenerative disease like Alzheimer's disease," Freedman says.
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