Yale School of Medicine: CNNR Program

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	Yale University School of Medicine CNNR Program
	P.O. Box 9812 New Haven, CT 06536-9812
	(203) 785-4736 Tel. (203) 785-5098 Fax

YUSM Logo

		Stephen M. Strittmatter, M.D., Ph.D.
		Vincent Coates Professor of Neurology Professor, Neurobiology Director, Yale Program in Cellular Neuroscience Neurodegeneration and Repair Member, Kavli Institute for Neuroscience
		Department of Neurology Yale University School of Medicine 295 Congress Ave BCMM 436C New Haven, CT 06520
		203.785.4878 fax: 203.785.5098 email: stephen.strittmatter@yale.edu

Stephen M. Strittmatter earned his undergraduate degree from Harvard College, summa cum laude, in 1980. He completed M.D. and Ph.D. training at Johns Hopkins in 1986 with mentorship from Solomon H. Snyder, M.D. He then moved to Massachusetts General Hospital for a medical internship and an Adult Neurology residency. While at Massachusetts General Hospital, he worked as a Research Fellow with Mark Fishman, M.D., exploring the molecular basis of axonal guidance. After a year as Fellow, he served briefly as an Assistant Professor at Harvard Medical School before moving to Yale University in 1993. He is currently holds the Vincent Coates Professorship of Neurology and co-founded the Yale Program in Cellular Neuroscience, Neurodegeneration and Repair. His research on axonal growth during development and regeneration has been recognized by honors from the Ameritec Foundation, the John Merck Fund, the Donaghue Foundation, the McKnight Foundation, the Jacob Javits Award of the NINDS and the American Academy of Neurology.

Research Statement

Our laboratory seeks to explain how axons are guided to the
correct sites during development and to describe the extent to
which axonal connectivity is fixed or malleable in the adult. Our
previous work has identified the myelin-derived inhibitory protein,
Nogo-A, and an axonal Nogo-66 Receptor (NgR1) as inhibitors of
axonal regeneration after adult brain or spinal injury. The natural
function of this system is to limit adult brain plasticity and to
reduce the risk of psychiatric disease. We are exploring the
physiological role of NgR in brain plasticity by imaging intact
neurons in living animals with a two-photon microscope through
windows in the skull. We are also developing blockers of this
system using structural biology, mutagenesis and high-throughput
screening methods. Such antagonists are now shown to exhibit
dramatic regenerative efficacy in the treatment of CNS injury,
including spinal cord trauma and stroke.

We have initiated studies in the neuronal degeneration in
Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD).
In both of these diseases, specific extracellular peptides are
implicated in the disease process, but the neuronal receptor which
mediates the peptide effect is not known. Using expression cloning
methods, we have identified high affinity binding sites for the Aß
oligomers of AD and the progranulin/granulin peptides of FTD.
We are characterizing the significance and receptor-type action
of these high affinity binding sites for Aß and Progranulin.

fig 1

fig 2

Recent Publications

Hu F, Strittmatter SM. The N-terminal domain of Nogo-A inhibits cell adhesion and axonal outgrowth by an integrin-specific mechanism. J Neurosci. 30:1262-1269 (2008).

Schmidt E, Shim SO, Strittmatter SM. Release Of MICAL Auto-inhibition By Semaphorin-Plexin Signaling Promotes Interaction With CRMP. J Neurosci. 28:2287-2297 (2008).

Budel S, Padukkavidana T, Liu BP, Feng Z, Hu F, Johnson S, Lauren J, Park JH, McGee AW, Liao J, Stillman A, Kim JE, Yang BZ, Sodi S, Gelernter J, Zhao H, Hisama F, Arnsten AF, Strittmatter SM. Genetic variants of Nogo-66 receptor with possible association to schizophrenia block myelin inhibition of axon growth. J Neurosci. 28:13161-13172 (2008).

Wang X, Budel S, Baughman K, Gould G, Song KH, Strittmatter SM. Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth. J Neurotrauma. 2009 Jan 6. [Epub ahead of print]

Linhoff MW, Laurén J, Cassidy RM, Dobie FA, Takahashi H, Nygaard HB, Airaksinen MS, Strittmatter SM, Craig AM. An Unbiased Expression Screen for Synaptogenic Proteins Identifies the LRRTM Protein Family as Synaptic Organizers. Neuron 61:734-749 (2009).

Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular Prion Protein Mediates Impairment of Synaptic Plasticity by Amyloid-ß Oligomers. Nature 457:1128-1132 (2009).

Key References

Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM. Collapsin-induced growth cone collapse mediated by an intracellular protein related to unc-33. Nature, 376: 509-514 (1995).

Takahashi T, Fournier A, Nakamura F, Wang, LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM. Plexin-neuropilin1 complexes form functional semaphorin-3A receptors. Cell 99: 59-69, (1999).

Grandpre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature, 403: 439-444 (2000).

Fournier A, GrandPre T, Strittmatter SM. Identification of a neuronal receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409:341-346 (2001).

GrandPre T, Li S, Strittmatter SM. Nogo-66 Receptor Antagonist Peptide Promotes Axonal Regeneration, Nature 417: 547-551 (2002).

Liu B, Fournier A, GrandPre T Strittmatter SM. Myelin-Associated Glycoprotein As A Functional Ligand For The Nogo-66 Receptor. Science, 297:1190-1193 (2002).

Kim JE, Li S, GrandPré T, Qiu D, Strittmatter SM. Axon Regeneration in Young Adult Mice Lacking Nogo-A/B. Neuron, 38, 187-199 (2003).

Kim JE, Liu BP. Park JH, Strittmatter SM. Nogo-66 Receptor Prevents Raphespinal and Rubrospinal Axon Regeneration and Limits Functional Recovery from Spinal Cord Injury. Neuron 44:439-451 (2004).

McGee W, Yang Y, Fischer QW, Daw N, Strittmatter SM. Experience-Driven Plasticity Of Visual Cortex Restricted By Myelin And Nogo Receptor. Science 309: 2222-2226 (2005).

Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular Prion Protein Mediates Impairment of Synaptic Plasticity by Amyloid-ß Oligomers. Nature 457:1128-1132 (2009).

Last modified: Friday, April 24, 2009 9:11 AM

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