- B.Sc., Universidad Central de Venezuela, 1991
- M.Sc., Instituto Venezolano de Investigaciones Cientificas, 1992
- Ph.D., London University, England, 1996
- Postdoc, New York University, 1998-2003
- Postdoc, London University, England, 1997
Actomyosin Regulation and Mechanism of Myelin Formation
Myelin is a highly specialized membrane, which wraps around nerve fibers in the peripheral (PNS) and central (CNS) nervous systems. While the function of the myelin sheath in facilitating the efficient and rapid propagation of nerve impulses has long been known, the mechanisms of its formation have remained elusive. During nerve development, Schwann cells in the PNS and oligodendrocytes in the CNS undergo a series of striking changes that ultimately lead to their maturation into specialized glial cells able to wrap around nerve fibers, and make myelin.
Very little is known about the mechanisms behind these morphogenetic events, but they are likely to involve a combination of structural cytoskeletal elements and force-generating molecules driving the extension of the plasma membrane and its coordinated movement around the axon. Candidate molecules to accomplish such roles are actin and the actin-associated motor protein myosin II. Using an in vitro co-culture system our laboratory is actively investigating the regulation of molecular motors during myelination by Schwann cells and oligodendrocytes.
The overall goal of our research is to provide novel insights into the mechanisms that regulate myelin morphology and formation in the PNS and CNS. A basic understanding of the molecular machinery of myelination should aid in the development of new therapeutic strategies to promote remyelination in pathological conditions such as multiple sclerosis.
- Lim, H., Sharoukhov, D., Kassim, I., Zhang, Y., Salzer, J.L., Melendez-Vasquez, C.V., Label-free imaging of Schwann cell myelination by third harmonic generation microscopy. Proc Natl Acad Sci. 2014 111(50):18025-30. doi: 10.1073/pnas.1417820111. Epub 2014 Dec 1
- Rusielewicz T, Nam J, Damanakis E, John GR, Raine CS, Melendez-Vasquez CV. Accelerated repair of demyelinated CNS lesions in the absence of non-muscle myosin IIB. Glia. 2014 Apr;62(4):580-91. doi: 10.1002/glia.22627. Epub 2014 Jan 28. PMID: 24470341.
- Dutta D, Zameer A, Mariani JN, Zhang J, Asp L, Huynh J, Mahase S, Laitman BM, Argaw AT, Melendez-Vasquez CV, Casaccia P, Hayot F, Bottinger EP, Brown CW and GR John. Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination. Development 2014 (12):2414-28. doi: 10.1242/dev.106492. PMID: 24917498
- Wang, H., Rusielewicz T., Leitman, E, Tewari, A., Melendez-Vasquez CV. Myosin IIB is a negative regulator of oligodendrocyte differentiation. (2012) J. Neurosci Res, 90(8):1547-56.
- Leitman E., Tewari A., Horn, M., Urbanski M., Damanakis, E., Einheber S., Salzer J., de Lanerolle P., Melendez-Vasquez, C.V. (2011) MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination. J Cell Sci 124: 3784-96. PMID: 22100921.
- Zhang J, Kramer E, Asp L, Dutta D, Navrazhina K, Pham T, Mariani J, Argaw A, Melendez-Vasquez CV, John GR. Promoting myelin repair and return of function in multiple sclerosis (2011). FEBS Letters 585:3813-20. PMID: 21864535.
- He, Y, Kim JY, Dupree J, Tewari A, Melendez-Vasquez, C, Svaren J, Cassacia, P (2010) Yy1: a molecular link between neuregulin and transcriptional regulation of peripheral myelination. Nat Neurosci 2010 13:1472-80. PMC3142946.
- Wang, H, Tewari A., Einheber S., Salzer J. and Melendez-Vasquez, Carmen V. (2008) Myosin II has distinct roles during PNS and CNS myelin sheath formation. J Cell Biol 182:1171-84
- Zhang Y., Taveggia C., Melendez-Vasquez, CV., Einheber S., Raine C S., Salzer J L., Brosnan C F and Gareth R. John (2006) Interleukin-11 potentiates oligodendrocyte survival and maturation, and myelin formation J.Neurosci 26: 12174-12185
- Melendez-Vasquez, C.V., Carey D., Zanazzi, G., Reizes, O., Maurel P., Salzer J.L. (2005) Differential expression of proteoglycans at central and peripheral Nodes of Ranvier Glia 52:301-308.
- John GR, Chen L, Rivieccio MA, Melendez-Vasquez CV, Hartley A, Brosnan CF.(2004) Interleukin-1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis. J Neurosci. 24: 2837-2845.
- Melendez -Vasquez, C.V., Einheber S., Salzer J.L (2004) Rho kinase regulates Schwann cell myelination and formation of associated axonal domains. J.Neurosci. 24:3953-3963
- Melendez-Vasquez, C.V., Rios, J.C., Zanazzi, G., Lambert, S., Bretscher, A. & Salzer, J. (2001) Nodes of Ranvier form in association with ERM (ezrin-radixin-moesin)-positive Schwann cell processes. Proc. Natl. Acad. Sci. 98:1235-1240
- Rios, J.C.*, Melendez -Vasquez, C.V*., Einheber, S., Lustig,M., Grumet, M., Gollan, L., Peles, E., Hemperly, J.J. & Salzer, J.L. (2000) Caspr and contactin co-localize in the paranodal and internodal membranes of myelinated axons. J. Neuroscience 20: 8354-8364. (*equal contribution).