SUMMARY
In the Meningeal Lymphatics and Neurological Disorders Laboratory at Mayo Clinic's campus in Jacksonville, Florida, Sandro Da Mesquita, Ph.D., and his team are exploring the role of the meningeal lymphatic system in brain physiology, aging, and degeneration.
In previous studies, Dr. Da Mesquita and colleagues have provided remarkable insights about the effects of impaired brain drainage by meningeal lymphatics on different aspects of brain function, behavior, and neuroinflammation. Studies performed in preclinical rodent models have shown that impaired meningeal lymphatic drainage of the brain impacts different neuropathological hallmarks of multiple sclerosis and Alzheimer's disease.
The overarching hypothesis raised in Dr. Da Mesquita's lab is that certain environmental and genetic factors can increase the risk of neurological disease, such as Alzheimer's disease. These factors appear to influence long-lasting changes in meningeal lymphatic vasculature, brain lymphatic drainage, and central nervous system immunity. To test this hypothesis, Dr. Da Mesquita's multidisciplinary team uses different experimental approaches, genetically modified mouse models, human brain and meningeal biospecimens collected postmortem, and state-of-the-art techniques such as single-cell RNA sequencing and mass cytometry.
Dr. Da Mesquita also is dedicated to recruiting and training researchers at career stages ranging from undergraduate to postdoctoral.
Focus areas
- Regulation of brain cell metabolism, physiology and function by meningeal lymphatic drainage.
- Alzheimer's disease risk factors, meningeal lymphatic function and central nervous system immunity.
- Cross talk between meningeal immunity and the lymphatic vasculature in aging and in neurological conditions.
- Mechanisms of therapeutic regeneration of the meningeal lymphatic system in older adults and the implications this system has in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis.
Significance to patient care
The number of new cases of age-related brain diseases is rising quickly. Recent studies show that aging leads to a higher risk of brain disorders. Aging also is associated with dysfunctional brain drainage. This happens when the meningeal lymphatic vasculature, which is found in humans and other animals, doesn't work properly. This allows too much fluid to build up.
Dr. Da Mesquita is working closely with other research labs at Mayo Clinic and beyond. He aims to create novel strategies to fix meningeal lymphatic vessel dysfunction and pathological brain immune responses in patients. His team also hopes to find new therapeutic targets to prevent brain diseases and serious memory loss by improving brain lymphatic drainage.