Harvard Medical School
Department of Neurobiology
The goal of our research is to understand the mechanisms of how nervous and vascular systems coordinately develop, communicate, and work in concert to ensure proper brain function.
The brain, which represents 2% of the body mass but consumes 20% of the body energy at rest, is therefore highly dependent on oxygen and nutrients supply from the blood stream. Key to the functional interdependence between neural and vascular systems is an extraordinarily tight physical association between neurons and endothelial cells, with nearly every neuron in the human brain estimated to be supplied by its own capillary. In addition, normal brain function requires a tightly controlled environment free of toxins and pathogens and with proper chemical compositions for synaptic transmission.
Understanding neurovascular interactions is a research area that bridges the fields of neuroscience and vascular biology. Both the anatomical and functional aspects of neurovascular interactions are best seen under in vivo settings (for example, our research has been conducted in the retina, basal ganglia system, and cortex), therefore the main approach we use in the lab is mouse genetics. Specifically, this methodology allows us to simultaneously observe both systems endogenously and use genetic manipulations to perturb one system and observe the resultant consequences in the other. To identify and characterize molecular signals underlying neurovascular interactions, we have also developed a variety of in vitro assays, screening strategies, and computational models. We then transfer the findings from these in vitro techniques back to the in vivo system for validation. We aim to understand the neurovascular interactions from a molecular level to a systems level.
Neurovascular biology is a relatively young field and much is to be discovered. In order to elucidate the functional aspects of neurovascular interactions, such as the mechanisms underlying the coupling between neural activity and vascular structure and dynamics, as well as the blood-brain barrier (BBB) formation and tightness, we must first understand and characterize the anatomical aspects of the neurovascular interactions. These basic characterizations and molecular identifications will provide important tools and premise for functional studies. Therefore my lab’s past and current research can be divided into two general directions- the mechanisms underlying the anatomical aspect of the neurovascular interactions, and the functional aspect of the neurovascular interactions.
(1) What are the cellular and molecular mechanisms governing the formation, function, and regulation of the blood brain barrier (BBB)?
(2) What are the mechanisms underlying the cross-talk between neural activity and vascular structure and dynamics?
(3) How do common guidance cues and their receptors function in wiring neural and vascular networks?
(4) What are the molecular mechanisms underlying the establishment of neurovascular congruency?
Last update: Febuary 25, 2014
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