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Neuroscience Graduate Program at UCSF
Axon Injury, Disease, and Novel Paradigms for Therapy
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.
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
Wesley Chang, Postdoctoral Fellow
Christina Fu, Neuroscience Student
Elizabeth Hawkes, Staff Research Associate
Durga Sarvepalli, Postdoctoral Fellow
Tony Tran, Staff Research Associate
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.
David Sretavan, M.D./Ph.D.
Phone
Office: 415-476-0840
Lab: 415-476-4135
Physical Address
Parnassus Campus
Koret Vision Research Building
Rm. K107, 110
Mailing Address
10 Kirkham Street
Rm. K107, Box 0730
University of California San Francisco
San Francisco, CA. 94143
For Internal Campus Mail
Box 0730
Other Websites
Biomedical Sciences Graduate Program
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research