Chenghua Gu, DVM, PhD

Assistant Professor of Neurobiology

Harvard Medical School
Department of Neurobiology
220 Longwood Avenue
Boston, MA 02115
Telephone: 617-432-6364
Fax: 617- 734-7557
Email: chenghua_gu@hms.harvard.edu
Predocs: 2 Postdocs:3 Completed PhD's: 0

Nervous and vascular systems share many features, despite their distinct functions. Developmentally, they are formedaround the same time, and both continue to dynamically remodel throughout life. Anatomically, they are both highly-branched and complicated networks; yet both networks have remarkably stereotyped patterns. Moreover, even from thetime of Vesalius and Da Vinci, it has been clear that nerves and vessels often run adjacent to each other. Functionally,neural activity and vascular dynamics are interdependent in the periphery and tightly coupled in the brain. Despite theimportance of this intimate relationship, little is known at the molecular level about how these two systems are coordinatelypatterned during development and what permits ongoing neurovascular interactions in the adult. The goal of our research isto understand the molecular mechanisms of how neural and vascular networks are coordinately developed, communicate,and evolve to work in concert during normal and disease states.

Using a combination of mouse genetics, cell biology, and biochemistry-based approaches, our research program currentlyexplores 4 topics: 1. Characterize the intriguing neurovascular anatomical relationship in the brain. 2. Identify the molecularsignaling cascade controlling neural and vascular patterning and their intercommunication. 3. Identify novel factors fromendothelial cells that control neuronal function and vice versa. 4. Address how patterning cues influence human disease,involving both neural and vascular damage and repair. To study these questions in vivo, we frequently use geneticallyengineered mouse models with specific mutations and tracers combined with imaging and physiological approaches. Tocomplement this work, we also perform studies in chick and a variety of in vitro assays to further reveal the mechanisms ofaction. With these approaches, we aim to understand the neurovascular interactions from a molecular level to a systems level.

References:

• 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.
• Gu, C., Rodriguez, E.R., Reimert, D.V., Shu, T., Fritzsch, B., Richards, L.J., Kolodkin, A.L., Ginty, D.D. (2003) Neuropilin-1 conveys Semaphorin and VEGF signaling during neural and cardiovascular development. Developmental Cell. 5 (1):45-57.
• Gu, C., Limberg, B.J., Whitaker, G.B., Perman, B., Leahy, D.J., Rosenbaum, J.S., Ginty, D.D., Kolodkin, A.L. (2002) Characterization of neuropilin-1 structural features that confer binding to semaphorin 3A and vascular endothelial growth factor 165. J Biol Chem. 17; 277(20):18069-76.