Chenghua Gu

  • Latest publications

    Andreone, B.J., Lacoste, B., Gu, C., (2015) Neuronal and vascular interactions. Annu Rev Neurosci. 38:25-46

    Chow.B.W., Gu, C., (2015) The molecular constituents of the blood-brain barrier. Trends Neurosci. 38(10):598-608

    Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B.J., Mayshar, Y., Yan, H., Gu, C., (2014) Mfsd2a is critical for the formation and function of the blood brain barrier. Nature, 509(7501):507-11.   PMC4134871. (News & Views in Nature 509(7501):432-3). (Preview in Neuron 82(4):728-30.)

    Lacoste, B., Comin C.H., Ben-Zvi, A., Kaeser, P.S., Xu, X., Costa, L.F., Gu, C., (2014) Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex. Neuron, 83(5): 1117-1130. PMC4166422.

    Oh, W., Gu, C., (2013) Establishment of neurovascular congruency in the mouse whisker system by an independent mechanism. Neuron. 80(2):458-469. PMC 3998758. (Preview in Neuron 80(2): 262-265).

  • Prizes and Awards

    NIH Director’s Pioneer Award, 2014

    Kaneb Fellow, 2013

    Armenise-Harvard Junior Faculty Grant, Department of Neurobiology: “Role of Semaphorins and their Receptors in Axon and Vascular Guidance”, 2009

    Sloan Research Fellowship, 2008

    Basil O’Connor Starter Scholar Research Award, March of Dimes Foundation, 2007

    Klingenstein Fellowship Award in the Neurosciences, 2007

    Ellison Medical Foundation New Scholar Award in Aging (declined due to the acceptance of other awards), 2007

    Whitehall Foundation Award, 2007

Who she is

Chenghua Gu is currently an associate professor in the Department of Neurobiology at Harvard Medical School. She did her PhD with Dr. Moses Chao at Cornell Medical School in New York city and her postdoctoral training with Dr. David Ginty at Johns Hopkins Medical School, Baltimore. Her laboratory studies the interface of two complex, structurally and functionally related systems in the brain, the nervous and vascular systems. Her laboratory employ genetically engineered mouse models with specific mutations and tracers combined with imaging and physiological approaches to reveal the neural and vascular networks in vivo. They also developed a variety of in vitro assays, screening strategies, and computational models to elucidate the mechanisms of action.

What she does

Her laboratory recently demonstrated that inhibition of transcytosis is a major mechanism for blood brain barrier (BBB) function, a surprising result in view of the nearly exclusive previous emphasis on the importance of tight junctions. By developing novel technology to monitor the BBB function, her lab discovered the first molecule that controls BBB permeability by inhibiting transcytosis, and a panel of other potential key molecular regulators. From the therapeutic standpoint, her findings suggest that molecules that inhibits transcytosis could be targets for opening the blood brain barrier. The lab is currently characterizing additional candidate genes and developing technologies to further understanding of the mechanisms controlling BBB formation and function.

A second research area concerns the role of neural activity in the regulation of vascular structure. Neuro-vascular interactions are best known in the control of hemodynamics, in which increased neural activity increases blood flow on timescales of seconds to minutes. However, whether neural activity influences the structure of vascular networks on longer timescales has not been studied. Her lab recently demonstrated that the remodeling of postnatal vascular networks is profoundly influenced by neural activity, which provides a novel mechanism for the brain to adequately match oxygen and nutrient supply to increasing energy demands.

In earlier studies, Dr. Gu’s lab contributed to the recognition that the same guidance cues and their receptors are used for wiring both the nervous and vascular systems, and discovered basic principles governing the establishment of neurovascular congruency.

News from the Lab

The current challenge of the BBB field is to identify essential molecular components and mechanisms that regulate its integrity. Two bottlenecks thwarting progress are the lack of an in vitro system to efficiently identify the key components from a large number of candidates, and the lack of an in vivo live imaging system to reveal real-time BBB physiology and study the dynamic mechanism of the key BBB genes. We have recently made progress towards solving the first bottleneck by developing an in vitro system that will not only allowing identifying a variety types of regulators (transcytosis, tight junctions, and master transcription), it will also allow reconstitute BBB in vitro with the identified minimal components.

Moreover, the imaging tools we are now building should produce a high pay off, not only in providing unparalleled resolution to study real time BBB physiology for the first time, but also in allowing investigation of the efficacy, speed, and reversibility of agents that perturb the BBB. This study, still under way, is financed by funds received from the NIH Director’s Pioneer Award.