Chenghua Gu profile picture
Chenghua Gu, Ph.D.
Professor of Neurobiology, Harvard Medical School

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. The general goal of our research is to understand the mechanisms of how neural and vascular systems coordinately develop, communicate, and work in concert to ensure proper brain function.

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 patterning and dynamics, as well as the blood brain barrier 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 aspects of these interactions. Using a combination of mouse genetics, cell biology, biochemistry, and various imaging techniques, our research program explores 4 questions:

(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?

Investigating interactions between the vascular and nervous systems is essential for better understanding of both brain function and underlying causes of neurological disorders, which will lead to new therapeutic strategies.

 

"The goal of our research is to understand the molecular mechanisms of how nervous and vascular systems coordinately develop, communicate, and work in concert to ensure proper brain function."

Publications View
Development and Cell Biology of the Blood-Brain Barrier.
Authors: Authors: Langen UH, Ayloo S, Gu C.
Annu Rev Cell Dev Biol
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Temporal modulation of collective cell behavior controls vascular network topology.
Authors: Authors: Kur E, Kim J, Tata A, Comin CH, Harrington KI, Costa Lda F, Bentley K, Gu C.
Elife
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Control of cerebrovascular patterning by neural activity during postnatal development.
Authors: Authors: Lacoste B, Gu C.
Mech Dev
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The molecular constituents of the blood-brain barrier.
Authors: Authors: Chow BW, Gu C.
Trends Neurosci
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Neuronal and vascular interactions.
Authors: Authors: Andreone BJ, Lacoste B, Gu C.
Annu Rev Neurosci
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Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2.
Authors: Authors: Keskin D, Kim J, Cooke VG, Wu CC, Sugimoto H, Gu C, De Palma M, Kalluri R, LeBleu VS.
Cell Rep
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A novel method for identifying a graph-based representation of 3-D microvascular networks from fluorescence microscopy image stacks.
Authors: Authors: Almasi S, Xu X, Ben-Zvi A, Lacoste B, Gu C, Miller EL.
Med Image Anal
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Neuropilin-1 functions as a VEGFR2 co-receptor to guide developmental angiogenesis independent of ligand binding.
Authors: Authors: Gelfand MV, Hagan N, Tata A, Oh WJ, Lacoste B, Kang KT, Kopycinska J, Bischoff J, Wang JH, Gu C.
Elife
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Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex.
Authors: Authors: Lacoste B, Comin CH, Ben-Zvi A, Kaeser PS, Xu X, Costa Lda F, Gu C.
Neuron
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Multiphasic modulation of cholinergic interneurons by nigrostriatal afferents.
Authors: Authors: Straub C, Tritsch NX, Hagan NA, Gu C, Sabatini BL.
J Neurosci
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