Postdoctoral researcher at UMass Chan University has received two fellowship awards in support of brain research

Violetta Doran-Lafort, Ph.D., will use spatial transcription technology to map senescent cells in the brain for the first time.

Violetta Doran-Lafort, MD, a postdoctoral researcher in the lab of Dorothy B. Shaffer, associate professor of neurobiology, has been awarded two fellowships totaling $375,000 to support her research into how cells in the brain affect aging.

New funding from BrightFocus Foundation Postdoctoral Fellowship Program in Alzheimer’s Disease Researchwhich supports young researchers in their final stages of targeted training, and Alzheimer’s Society Research Fellowshipfor researchers doing work related to Alzheimer’s disease and dementia.

Schafer’s lab studies how microglia regulate neural circuits in healthy and diseased nervous systems. The lab showed that these cells are able to ‘eat’ the synaptic connections between neurons to sculpt developing neural circuits and ‘overeat’ in the early stages of neurological disease to scavenge circuits. The lab is working to understand how these cells stimulate and spread inflammation in brain circuits with a focus on multiple sclerosis and Alzheimer’s disease.

Microglia are the resident immune cells in the brain. They exist to protect us from various inflammatory insults such as pathogens or injury, but they can also have roles in propagating the inflammatory process in various diseases and even ageing, Dr. Doran Laforet explained.

Cellular senescence is a frequently occurring process in aging in which cells stop dividing and begin producing inflammatory mediators. With the BrightFocus Prize, Duran Laforet will use a spatial transcription technique called MERFISH to map aging cells in the brain for the first time. These cells eventually stop reproducing but do not die when they should, continuing to release factors that can lead to inflammation.

“It has been shown that if you remove senescent cells from the brain in a mouse model of Alzheimer’s disease, the pathology improves. Moreover, senescent cells have been detected in the brains of Alzheimer’s patients. This gives us evidence that senescent cells are doing something in Alzheimer’s disease – It damages the brain and is involved in this pathology,” Doran Laforet said.

Using technology funded by a Massachusetts Life Sciences Center grant, Drs. Schaeffer and Christina Bayer, Ph.D., assistant professor of Microbiology and Physiological Systems, in 2020, Doran Laforet will be able to take a slice of tissue, and without losing the coordinates for each individual cell, study the expression genetics of those cells.

“Our thought is that this could be the starting point for many studies because this hasn’t been done before. Maybe we find that senescent cells are restricted to a specific area, and then we can develop new drug strategies. This will allow us to target future treatments for Alzheimer’s and any disease It has an aging component,” Doran Laforet said.

The Alzheimer’s Association award will fund Duran Laforet’s investigation into a subset of microglia known to reside at the site of blood vessels. This type of microglia is implicated in the pathogenic changes that occur in Alzheimer’s disease in the blood vessels. Durán will use Laforet MERFISH again, this time to interrogate the specifics of microglia associated with blood vessels to see how they change with age and neurodegeneration.

Duran Laforet said she has long been interested in neurodegenerative diseases and everything related to the brain. While earning her undergraduate degree in pharmacy from the Complutense University of Madrid, she joined the Neurovascular Research Unit, combining a new fascination with the brain with an interest in the immune system. She received her PhD in Biomedical Research from the same school. During the final year of her doctoral program, she came to Massachusetts to study with Eng Lo, Ph.D., professor of neuroscience and radiology at Harvard Medical School. I arrived at UMass Chan in early 2021 to work in the Schafer Lab.

Related UMass Chan news story:
Capital Funding of the Massachusetts Life Sciences Center to support three programs at the College of Medicine