Advancing the Science

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November 10, 2020

Advancing neuroscience at Mayo Clinic in Florida: Dr. Sandro Da Mesquita

By Advancing the Science contributor

Sandro Da Mesquita, Ph.D., has a new lab in the Birdsall research building and hopes team science leads to new approaches aimed at preventing neurodegeneration and cognitive decline in patients. His research focuses on neuroscience and neuroimmunology. Here he explains what guided him to pursue a medical research career.
What is your background?

I am a biochemist by training and performed all of my graduate studies in Portugal, at the School of Medicine of the University of Minho, located in a northern Portuguese city called Braga. It was in grad school that I started to develop a particular taste for neuroscience and cellular and molecular mechanisms underlying neuroinflammatory and neurodegenerative diseases. After defending my Ph.D. in health sciences, I decided it was time to get out of my comfort zone geographically, culturally, and scientifically speaking, so my wife and I immigrated to the U.S. in search of new challenges and better opportunities. I joined the laboratory of Jonathan Kipnis, Ph.D., at the University of Virginia School of Medicine (now at the Washington University School of Medicine in St. Louis), as a postdoctoral research associate.

Why/how did you get into your particular field?

In grad school, I was exploring the role of a brain barrier tissue, choroid plexus, in modulating cerebrospinal fluid composition in health and disease. The choroid plexus serves as one of the barriers of brain tissue and promotes a very tight exchange between the periphery (namely the blood) and the brain. By the time I finished grad school, there was this very interesting study from the Kipnis Lab, showing that there was a bona fide lymphatic vascular system in the meninges (another tissue that serves as a brain-periphery interface) wrapping brain and spinal cord. This work shattered previous misconceptions, dogmas even, in the field, because it showed that the central nervous system meningeal lymphatic vessels were directly connected to the peripheral lymphatics and constantly draining brain fluids, molecules and immune cells. For a young researcher like me, who was studying cerebrospinal fluid renewal and neuroimmune interactions in Alzheimer’s disease, this was mind-blowing. I was lucky enough that Dr. Kipnis gave me a shot at pursuing my postdoctoral studies in his lab, where we discovered that the meningeal lymphatic vasculature becomes functionally impaired with aging, and that this has a significant impact on brain function, cognition and several aspects of Alzheimer’s disease pathophysiology.

From Portugal to Virginia, to Jacksonville, Florida, what led you to Mayo Clinic?

I feel like history speaks for itself when it comes to neuroscience research at Mayo Clinic. It has been an institution where health care is the number one concern, which is only possible when it is backed-up by state-of-the-art basic scientific research developments. In terms of neuroscience research, and more precisely research about age-associated neurodegenerative diseases, the Department of Neuroscience at Mayo Clinic in Florida has been the hub for major discoveries regarding the pathological mechanisms underlying devastating disorders. These include amyotrophic lateral sclerosis (ALS), frontotemporal dementia and Alzheimer’s disease, all with increasing incidence in our society due to improved longevity. I will be another one who will do my best to push neuroscience forward at Mayo Clinic, advance our knowledge about these diseases and come up with effective treatments.

What research projects will you be working on at Mayo? Will you be collaborating with any other principal investigators?

Together with my team members, we will be focused on exploring the role of the meningeal lymphatic system in brain physiology, aging and degeneration. Our overarching hypothesis is that certain lifestyle/environmental (like diet, brain trauma or infections) and/or genetic factors (such as APOE4 in Alzheimer’s) increase the risk for neurological disease by mediating long-lasting changes in meningeal lymphatic vasculature, brain lymphatic drainage and central nervous system immunity. In order to test this, we will use different experimental approaches, genetically-modified mouse models, post-mortem collected human brain/meningeal biospecimens, and state-of-the-art techniques, such as single-cell RNA sequencing and mass cytometry. Specific research focus areas in the Da Mesquita Lab will include:

  • Regulation of brain cell metabolism, physiology and function by meningeal lymphatic drainage
  • Mechanisms of therapeutic regeneration of the aged meningeal lymphatic system and its implications to neurodegenerative diseases (Alzheimer’s, Parkinson’s and frontotemporal dementia)
  • Alzheimer’s disease risk factors and meningeal lymphatic function
  • Crosstalk between meningeal immunity and the lymphatic vasculature in aging and in neurological disorders

Research will always result from a team effort. Because our work intersects with so many different areas of interest, we expect to find Mayo Clinic a rich source of potential collaborations, and add to those both national and international team members as relevant.

What moment/experience in your life led you to pursue a medical research career?

I am not sure if there was really a moment that I can pinpoint, but perhaps it was when I started to take immunology classes in college. I realized how important the role of medical researchers has been for the development of all major therapies and treatments we are using in our daily life. Sometimes people are not aware that the pill or medication they are taking resulted from many hours, months, or years of work performed in a laboratory by medical researchers somewhere around the world. I guess the fact that I realized that early-on shaped my career somehow, and it still gives me the motivation to find answers to important scientific questions.

What do you hope your research will do for patients? How do you hope to change the practice?

The incidence of age-related neurological disorders is rapidly increasing. Recent experimental evidence shows that aging leads to both increased risk for brain disorders and for dysfunctional brain drainage by the meningeal lymphatic vasculature (found in different vertebrate species, including humans). Through close collaboration with other laboratories within the Mayo Clinic universe (and beyond), my research team ultimately aims to develop 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.

Do you have any interesting hobbies?

I really enjoy going for a run outdoors and playing soccer with friends. I still haven’t had the chance to play soccer here in Jacksonville, mostly due to the special precautions (social distancing) we all have to take because of the COVID-19 pandemic. My wife and I have been able to go outdoors for some long strolls with our dog, mostly at the beach during less busy hours. Jacksonville is a really nice city. It’s very affordable and there are many choices in terms of outdoor activities.

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Tags: ALS, Alzheimer's disease, amyotrophic lateral sclerosis, brain, cognitive impairment, dementia, immune system, lymphatic system, neuroimmunology, neurosciences, News, People, research education, Sandro Da Mequita

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