Violeta Durán Laforet, PhD, a post-doctoral fellow in the lab of Dorothy P. Schafer, PhD, associate professor of neurobiology, has received two grants totaling $375,000 to support her research on how brain cells affect aging.
The new funding comes from the BrightFocus Foundation Postdoctoral Fellowship Program in Alzheimer’s Disease Research, which supports young researchers in the final stages of their mentored training, and from the Alzheimer’s Association Research Fellowship, for researchers carrying out work related to Alzheimer’s disease. and dementia.
The Schafer lab studies how microglia regulate neural circuits in healthy and diseased nervous systems. The lab has shown that these cells are able to “eat” the synaptic connections between nerve cells to sculpt developing neural circuits and “overeat” in the early stages of neurogenerative disease to dismantle the circuits. The lab works to understand how these cells trigger and propagate inflammation in brain circuitry, with a focus on multiple sclerosis and Alzheimer’s disease.
“Microglia are the resident immune cells of the brain. They are there to protect us from different inflammatory insults such as pathogens or injuries, but they can also play a role in spreading the inflammatory process in different diseases and even in aging,” explained Dr. Durán Laforet.
Cellular senescence is a process that frequently occurs during aging in which cells stop dividing and begin to produce inflammatory mediators. With the BrightFocus award, Durán Laforet will for the first time use a spatial transcriptomics technique called MERFISH to map senescent brain cells. These cells eventually stop multiplying but don’t die when they should, continuing to release factors that can trigger inflammation.
“It has been shown that if you remove senescent cells from the brain of an Alzheimer’s mouse model, the pathology improves. In addition, senescent cells have been detected in the brains of patients with Alzheimer’s disease. So this gives us a clue that senescent cells are doing something in Alzheimer’s disease: they are damaging the brain and participating in this pathology,” said Durán Laforet.
Using technology funded by a Massachusetts Life Sciences Center grant, Dr. Schafer and Christina Baer, PhD, assistant professor of microbiology and physiological systems, received in 2020, Durán Laforet will be able to take a slice of tissue and, without losing the coordinates of each cell, study the gene expression of these cells.
“Our thought is that this could be the starting point for many more studies because it has never been done. Perhaps we will discover that senescent cells are restricted to a certain area, and then we can develop new pharmacological strategies. This will allow us to target future treatments for Alzheimer’s disease and any disease with a senescent component,” said Durán Laforet.
The Alzheimer’s Association award will fund Durán Laforet’s investigation of a subset of microglia known to reside in a vascular niche. This type of microglia has been implicated in the pathogenic changes that occur in Alzheimer’s disease in blood vessels. Durán Laforet will again use MERFISH, this time to interrogate the particularities of microglia associated with blood vessels to see how they change with aging and neurodegeneration.
Durán Laforet said she has had a long interest in neurodegenerative diseases and anything 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 for the brain with an interest in the immune system. She received her doctorate in biomedical research from the same school. During the final year of the doctoral program, she came to Massachusetts to study with Eng Lo, PhD, professor of neurology and radiology at Harvard Medical School. She came to UMass Chan in early 2021 to work in Schafer’s lab.
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