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: 4 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.

Using a combination of mouse genetics, cell biology, biochemistry, and imaging techniques, our research program currently explores 5 topics:
1. Uncover the molecular mechanisms underlying the neurovascular congruency during development. 2. Characterize how common guidance cues and their receptors function in wiring neural circuitry and shaping up the vascular topology. 3. Characterize the intriguing neurovascular anatomical relationship in the brain, including how neural activity changes vascular network. 4. Identify novel factors from endothelial cells that control neuronal function and vice versa, including the factors control the blood brain barrier formation. 5. Address how patterning cues influence human disease, involving both neural and vascular damage and repair.
To study these questions in vivo, we use genetically engineered mouse models with specific mutations and tracers combined with imaging and physiological approaches. To complement this work, we also perform studies in chick and a variety of in vitro assays to further reveal the mechanisms of action. With these approaches, we aim to understand the neurovascular interactions from a molecular level to a systems level.



Last Update: 1/13/2014



Publications

For a complete listing of publications click here.

 


 

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. 2011 Dec 18. doi: 10.1038/nn.3003. [Epub ahead of print]

Kim, J., Oh, W., Gaiano, N., Yoshida, Y., Gu, C., (2011) Semaphorin 3E-Plexin-D1 signaling regulates VEGF function in developmental angiogenesis via a feedback mechanism.
Genes & Development. 25 (13):1399-411.

De Almodovar,C.,Fabre, P., Knevels, E., Coulon,C., Segura, I., Haddick, P., Aerts, L., Delattin, N., Strasser, G., Oh, W., Lange, C., Vinckier, S., Haigh, J., Fouquet,C., Henderson, C., Gu, C., Alitalo, K., Castellani, V., Tessier-Lavigne, M., Chedotal, A Charron, F., Carmeliet, P., (2011) VEGF mediates commissural axon chemoattraction through its receptor Flk1.
Neuron. 70(5):966-78.

Gelfand, M. V., Hong, S., Gu, C., (2009) Guidance from above: common cues direct distinct signaling outcomes in vascular and neural patterning.
Trends in Cell Biology. 19(3):99-110.

Gu, C., Yoshida, Y., Livet, J.,Reimert, D.V., Mann, F., Merte, J., Henderson, C.E., Jessell, T.M., Kolodkin, A.L., Ginty, D.D. (2005) Semaphorin3E and Plexin-D1 control vascular pattern independently of Neuropilins.
Science. 307 (5707):265-268.



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