Chenghua Gu profile picture

Chenghua Gu, PhD

Professor of Neurobiology
Investigator, Howard Hughes Medical Institute

The brain, which represents 2% of the body mass but consumes 20% of the body energy at rest, is highly dependent on a continuous supply of oxygen and nutrients from the blood stream. To accommodate this high demand, blood vessels  in the brain differ from the rest of the body. First, brain blood vessels have a gate, called the Blood-Brain Barrier (BBB), that permits vital nutrients to pass into the brain, but blocks the entry of harmful viruses and bacteria. While the selectivity of the BBB is beneficial to the brain, it comes at a cost: the gate is so selective that it can block the entry of therapeutic agents. Moreover, a leaky, non-selective BBB is one of the earliest features in many neurological diseases. Thus, a major challenge is to identify ways of manipulating the BBB to transiently open the barrier to deliver drugs, or to tighten the barrier to delay progression of neurodegeneration.

Second, blood vessels in the brain are functionally coupled to neural activity, such that neural activity rapidly increases local blood flow to meet moment-to-moment changes in regional brain energy demand. Neurovascular coupling is also the basis for functional brain imaging in human. We are exploring how this process influences neural function and behavior.

Third, the brain vasculature is the first line of contact between the brain and the periphery as systemic circulation contains factors released from all organs. So, any substance that affects the brain must first talk to brain endothelial cells. For example, peripheral inflammation profoundly influences brain health. We are investigating how  brain endothelial cells transmit peripheral immune signals to the brain.

How the brain vasculature carries out these diverse and critical functions by interacting with the systemic and brain factors to control brain’s own environment and energy is an important and largely uncharted research area.

The goal of our research is to understand the molecular and cellular mechanisms underlying BBB function and neurovascular coupling. Achieving our goals could have a big impact on therapeutics and change how neurological diseases are treated.

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.
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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.
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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.
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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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