In his laboratory in the Department of Neuroscience 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 (MS) and Alzheimer's disease (AD).
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 AD. 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 post-mortem, and state-of-the-art techniques such as single-cell RNA sequencing and mass cytometry.
Dr. Da Mesquita also is dedicated to the recruitment and training of researchers at career stages ranging from undergraduate to postdoctoral.
- Regulation of brain cell metabolism, physiology and function by meningeal lymphatic drainage.
- AD 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 AD, Parkinson's disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
Significance to patient care
The incidence of age-related neurological diseases is rapidly increasing. Recent experimental evidence shows that aging leads to increased risk of brain disorders. Aging is also associated with dysfunctional brain drainage. This happens when the meningeal lymphatic vasculature, found in different vertebrate species including humans, fails to work properly, allowing excess fluid to accumulate.
By closely collaborating with research laboratories within Mayo Clinic and beyond, Dr. Da Mesquita's ultimate goals are to develop novel strategies to detect and correct meningeal lymphatic vessel decay and pathological brain immune dysregulation in patients. His group also hopes to identify translational therapeutics aimed at preventing neurodegeneration and severe cognitive decline by improving brain lymphatic drainage.