BBS Faculty Member - Chenghua Gu

Chenghua Gu

Department of Neurobiology

Harvard Medical School
Armenise Building, Room 315
220 Longwood Ave.
Boston, MA 02115
Tel: 617-432-6364
Fax: 617-734-7557
Email: chenghua_gu@hms.harvard.edu
Lab Members: 6 postdoctoral fellows, 2 students
Visit my lab page here.



Proper function of precisely wired neural circuits depends on a close physical and functional relationship with an equally complex and overlapping network of blood vessels. Blood vessels provide neurons with oxygen and nutrients and protect them from toxins and pathogens. Nerves, in turn, control blood vessel dilation and contraction and also heart rate. Key to this functional interdependence 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. Indeed, recent evidence suggests that neurodegenerative diseases once thought to be caused by intrinsic neuronal defects are in fact initiated and perpetuated by vascular abnormalities. However, despite the importance of this intimate relationship, how the nervous system becomes closely aligned with the vascular system during development and what molecular signals permit ongoing neurovascular interactions in the adult remains mystery. The goal of our research is to understand the molecular mechanisms of how neural and vascular networks are coordinately developed, communicated, and evolve to work in concert during normal and disease states.

Neurovascular biology is a relatively young field and very little is currently known. In order to elucidate the functional aspects of neurovascular interactions, such as the mechanisms underlying the coupling between neural activity and vascular dynamics or 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.Using a combination of mouse genetics, cell biology, biochemistry, and imaging techniques, our research program currently explores 4 topics:

(1) What are the molecular mechanisms underlying the establishment of neurovascular congruency?
(2) How do common guidance cues and their receptors function in wiring neural circuitry and shaping vascular topology?
(3)What are the mechanisms underlying the cross-talk between neural activity and vascular dynamics?
(4) What are the molecular mechanisms governing the formation of a functional blood brain barrier (BBB)?



Last Update: 6/9/2014



Publications

For a complete listing of publications click here.

 


 

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.
(News & Views in
Nature 509(7501):432-3).
(Preview in
Neuron 82(4):728-30.)

Tata, A., Stoppel, D., Hong, S., Ben-Zvi, A., Xie, T.,
Gu, C., (2014) An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphoring 3E-PlexinD1 signaling. JCB, 205(4):573-590.

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).

Ding, J.B., Oh, W., Sabatini, B.L.,
Gu, C., (2011) Semaphorin3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nature Neuroscience. 15(2):215-23. PMC3267860

Kim, J., Oh, W., Gaiano, N., Yoshida, Y.,
Gu, C., (2011) Semaphorin3E-Plexin-D1 signaling regulates VEGF function in developmental angiogenesis via a feedback mechanism. Genes & Development. 25(13):1399-411. PMC3134083
(News and Views in
Dev Cell. 2011 16;21(2):189-90.)



© 2014 by the President and Fellows of Harvard College