Multidisciplinary team awarded CCTR Endowment Fund grant to investigate accelerated brain aging

By Christopher Richmond

A multidisciplinary Virginia Commonwealth University research team has been awarded a multi-school CCTR Endowment Fund grant from the C. Kenneth and Dianne Wright Center for Clinical and Translational Research to investigate the root causes of accelerated brain aging.

The project — “Investigating Astrocytes as Agents of Accelerated Brain Aging from a Neurodevelopmental Perspective” — is led by three researchers spanning multiple disciplines:

• Mathula Thangarajh, M.D., Ph.D., associate professor in the Department of Neurology at the VCU School of Medicine and a 2021 Wright Center KL2 Scholar.
• Tomasz Kordula, Ph.D., professor in the Department of Cellular, Molecular, and Genetic Medicine at the VCU School of Medicine.
• Preetam Ghosh, Ph.D., professor in the Department of Computer Science at the VCU College of Engineering.

The team is studying neuroinflammation — a driver of brain aging in which astrocytes become toxic to neighboring cells — through the lens of dystrophinopathy, a genetic condition caused by the absence of the protein dystrophin. Preliminary work in preclinical models found that astrocytes lacking dystrophin express high levels of aging-related genes, particularly prostaglandin D2. Using spatial transcriptomics, behavioral testing, and computational modeling, the researchers will test whether blocking prostaglandin D2 receptors reduces astrocyte-specific inflammation and improves behavior. Their work could point to new drug targets in dystrophinopathy and other neurodegenerative conditions.

The award builds on Thangarajh’s research into the neurological manifestations of muscular dystrophy. She treats children with neuromuscular diseases at Children’s Hospital of Richmond at VCU. Thangarajh was a Wright Center KL2 Scholar in 2021, which provided two years of protected research time and structured mentorship. This grant will support the team’s translational effort to address cognitive problems in dystrophinopathy.

Thangarajh responded to the news by saying, “The continued investment of CCTR in supporting my research provides me the welcome opportunity to extend the work that began in my KL2 project. Several noteworthy elements of the KL2 are reflected in this project — the multiteam collaboration and the true interdisciplinary approach.”

The Wright Center’s CCTR Endowment Fund backs research that applies laboratory discoveries to clinical trials and deepens understanding of the biological mechanisms behind clinical manifestations.

The Wright Center’s multi-school grants provide up to $130,000 to teams with collaborators from at least two VCU schools across the MCV and Monroe Park campuses, helping researchers generate the preliminary data needed for external funding. The Wright Center has been administering the endowment funds program since 2012.

Learn more about CCTR Endowment funds at cctr.vcu.edu/support/funding/endowment-fund-grants/.