My research is focused on understanding molecular mechanisms controlling peripheral nerve development with emphasis on regulation of growth and differentiation of Schwann cells into myelin-forming cells. Major pathways examined are transduction of extracellular matrix signals through integrin receptors and neuregulin signalling through erbB2/erbB3 receptors. The integration of these pathways with those regulating cytoskeleton organization through the rho family of GTPases is under study.
We have found that schwannomin/merlin the product of the Neurofibromatosis type 2 gene is a direct binding protein with paxillin, an integrator of extracellular matrix and growth factor signalling with changes in the actin cytoskeleton. The interacting domain in schwannomin is mutated in humans with NF2 mutations and leads to tumor formation.
The studies are conducted using primary Schwann cells in isolation or together with sensory neurons to study development of myelin in vitrol. These studies are funded by a long-standing grant from NIH/NINDS and have application for the understanding of various demyelinating diseases as well as abnormal growth of Schwann cells.
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- Sparrow N*, Manetti M, Bott M, Bates, M, Bunge MB, Lambert, S, Fernandez-Valle C. (2012) The Actin Severing Protein Cofilin is Downstream of Neuregulin Signaling and is Essential For Schwann Cell Myelination. J Neuroscience. 32:5284-97.
- Douglass. Sparrow, Bott, Fernandez-Valle, Dogariu. 2012Measuring Anisotropic Cell Motility on Curved Substrates. J Biophotonics (doi: 10.1002/jbio.201200089.)
- Manetti, Geden, Bott, Sparrow, Lambert, Fernandez Valle. 2012 Stability of the tumor suppressor merlin depends on its ability to bind paxillin LD3 and associate with β1 integrin and actin at the plasma membrane. Biology Open (doi: 10.1242/bio.20122121; 1, 949-957.)
- Thaxton C*, Bott M, Walker B, Sparrow NA*, Lambert S, and Fernandez-Valle C. 2011. Schwannomin Promotes Process Extension and Determines Internodal Myelin Length. Mol Cell Neuroscience. 47:1-9.
- Iacovelli J, Lopera J, Bott M, Baldwin ME, Khaled A, Uddin N, Fernandez-Valle C (2007). Serum and forskolin cooperate to promote G1 progression in Schwann cells by differentially regulating cyclin D1, cyclin E1, and p27Kip expression. Glia 55(16): 1638-47.
- Thaxton C, Lopera J, Bott M, Fernandez-Valle C (2007) Neuregulin and laminin stimulate phosphorylation of the NF2 tumor supressor in Schwann cells by distinct protein kinase A and p21-activated kinase-dependent pathways. Oncogene. doi: 10.1038/sj.onc.1210923.