In his laboratory in the Department of Neuroscience on Mayo Clinic's campus in Jacksonville, Florida, Sandro Da Mesquita, Ph.D., and his team focus on exploring the role of the meningeal lymphatic system in brain physiology, aging and degeneration. In previous studies, Dr. Da Mesquita and colleagues have provided singular insights about the effects of impaired brain drainage by meningeal lymphatics on different aspects of brain function, behavior and neuroinflammation, as well as on 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 factors, such as diet, brain trauma or infections, and genetic factors such as APOE4 and ABCA7 in AD, or C9ORF72 and GRN in frontotemporal dementia (FTD) increase the risk of neurological disease by mediating long-lasting changes in meningeal lymphatic vasculature, brain lymphatic drainage and central nervous system immunity. To test this hypothesis, Dr. Da Mesquita and his multidisciplinary team use different experimental approaches, genetically modified mouse models, postmortem-collected human brain and meningeal biospecimens, and state-of-the-art techniques such as single-cell RNA sequencing and mass cytometry.
Dr. Da Mesquita is also 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
- 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 and FTD
- AD risk factors and meningeal lymphatic function
- Cross-talk between meningeal immunity and the lymphatic vasculature in aging and in neurological disorders
Significance to patient care
The incidence of age-related neurological disorders is rapidly increasing. Recent experimental evidence shows that aging leads both to increased risk of brain disorders and to dysfunctional brain drainage by the meningeal lymphatic vasculature (found in different vertebrate species, including humans). By closely collaborating with other laboratories within Mayo Clinic and beyond, Dr. Da Mesquita's ultimate goals are to develop both novel strategies to detect meningeal lymphatic vessel decay in patients and translational therapeutics aimed at preventing neurodegeneration and severe cognitive decline by improving brain lymphatic drainage.