Harvard Medical School
Department of Neurobiology
Our research aims to further the understanding of how nervous and vascular systems develop, communicate, and work in concert to ensure proper brain function.
While the brain represents 2% of the body mass, it uses 20% of the body's energy at rest. This use of energy depends upon oxygen and nutrients supplied from the bloodstream. Thus three unique features of supplying blood to the brain exist to ensure normal functioning of neural circuits. First, the brain is densely vascularized to meet its high metabolic demand. All neurons in the brain lie within 50 microns of the nearest capillary. Second, there is a functional coupling between neural activity and blood flow because during normal behavior, there are moment-to-moment changes in regional brain metabolic demand: these regions must be brought "online" quickly. Third, blood vessels in the brain comprise the blood-brain barrier that provides a tightly controlled environment free of toxins and pathogens and with proper chemical compositions for synaptic transmission. This ensures normal brain function.
The study of neurovascular interactions bridges the fields of neuroscience and vascular biology. Both the anatomical and functional aspects of neurovascular interactions are best seen under in vivo settings, such as the retina, basal ganglia system, and cortex. Thus, the main approaches we use in the lab are mouse genetics and more recently also zebra fish. These methodologies allow us to simultaneously observe both systems endogenously. More specifically, they allow us to use genetic manipulations to perturb one system and to observe the resultant consequences in the other. In order to identify and characterize the 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. Finally, in order to establish the mechanisms that operate in vivo under normal physiological conditions, we have recently built a custom designed two-photon microscope to monitor neuro-vascular coupling and the blood-brain barrier permeability dynamics by imaging through cranial windows in awake mice. 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 crosstalk 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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