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Neuroscience Graduate Program at UCSF

Faculty - David Sretavan, M.D./Ph.D.

Axon Injury, Disease, and Novel Paradigms for Therapy


Research Description

My lab is actively engaged in research on nerve and axon responses to injury, disease, and on novel methods for nerve repair.  Our interest in these areas is built upon previous work from the laboratory on developmental molecules that control axon growth and behavior during formation of the nervous system.  Collectively known as axon guidance molecules, these proteins bind receptors on cells to activate signaling pathways to fundamentally regulate cytoskeletal assembly/disassembly and calcium handling. Our research group is particularly interested in the functional roles axon guidance molecules may have in the adult nervous system, specifically in the settings of CNS injury and disease.  In recent work we have found that EphB3, a member of the EphB family of receptor tyrosine kinases is involved in the initial sprouting response of retinal ganglion cell axons following optic nerve damage.  In addition, the up-regulation of members of the EphB and ephrin-B families is also detected in more chronic-progressive forms of injury such as glaucoma, where retinal axon damage is thought to contribute to the neurodegeneration of retinal ganglion cells.

A new research area for the laboratory is the use of micro and nanosystems as enabling technology for axonal repair.  Methodologies for silicon-based fabrication can be combined with sensing and actuation principles to form biomedical devices that operate at the micron length scale of single cells.  This field of Micro ElectroMechanical Systems (MEMS) engineering, coupled with advances in nanoscience may open up new frontiers in biological research, medical diagnostic & therapeutics.  The Sretavan laboratory is working with a multidisciplinary group of researchers in MEMS engineering, nanoscience, biophysics, neurobiology and neurosurgery, to develop a microsystem platform for the microsurgical reconstruction and repair of single axons. 

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Current Projects

EphB and ephrin-B function and RGC axon injury in glaucoma

Reconstitution of axon function following microscale repair

Customizable molecular micropatterning for neuron and axonal arrays in culture

Development of a microscale axon experimental platform

 


Lab Members

Wesley Chang, Postdoctoral Fellow
Christina Fu, Neuroscience Student
Elizabeth Hawkes, Staff Research Associate
Durga Sarvepalli, Postdoctoral Fellow
Tony Tran, Staff Research Associate

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Selected Publications

Link to Publications via PubMed

Sretavan, D. Chang, W., Keller, C. Kliot, M.  Microscale Surgery On Single Axons. Neurosurgery 57: 635-646, 2005.

Chang, W., Keller, C., Sretavan, D.   A Simple Microfabricated Cutting Device For The Isolation of Neuronal Subcellular Compartments. J. Neurosci. Methods. 152: 83-90, 2006.

Liu, X., Hawkes, E., Ishimaru, T., Tran, T., Sretavan, D.  EphB3 : An Endogenous Mediator of Adult Axon Plasticity After CNS Injury. J. Neurosci. 26: 3087-3101, 2006.

Chang, W., Hawkes, E., Kliot, M., Sretavan, D.  In Vivo Use Of A Nanoknife For Axon Microsurgery. Neurosurgery. 61: 683-692, 2007.

Du, J., Tran, T., Hawkes, E., Sretavan, D. Up-regulation of EphB2 And ephrin-B2 Coincide With Axon Loss At The Optic Nerve Head of DBA/2J Glaucomatous Mice. Invest. Ophthal. Vis. Sci. 48: 5567-5581, 2007.

Chang, W., Sretavan, D.  Novel High-Resolution Micropatterning for Neuron Culture Using Poly-lysine Adsorption On A Cell Repellant, Plasma Polymerized Background. Langmuir. 24: 13048-13057, 2008.

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David Sretavan, M.D./Ph.D.



Email

sretavand@vision.ucsf.edu

Phone

Office: 415-476-0840
Lab: 415-476-4135

Ofrice Address

UCSF Box 0730
Koret Vision Research Building
10 Kirkham Street, room K-107
San Francisco, CA 94143

Other Websites

Biomedical Sciences Graduate Program

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

Lab Website

PIBS Website