Carmen V. Melendez-Vasquez, Associate Professor
Lab Web Sitehttp://melendez.bioweb.hunter.cuny.edu
- Postdoc 1998-2003 New York University School of Medicine
- Postdoc 1997 London University, England
- PhD 1996 London University, England
- MSc 1992 Instituto Venezolano de Investigaciones Cientificas
- BSc 1991 Universidad Central de Venezuela
Cytoskeletal Regulation of Myelin Formation & Repair
Myelin is a specialized membrane, which wraps around axons in the peripheral (PNS) and central (CNS) nervous systems. In diseases such as Multiple Sclerosis (CNS) and Guillain-Barre Syndrome (PNS), loss of myelin around the nerve cells results in conduction block and underlies the clinical deficit characteristic of these disorders. Remyelination restores nerve conduction and leads to resolution of symptoms. However there are currently no treatments designed to directly target the efficiency of myelin repair and the return of nerve function. Our studies focus on the role of cytoskeletal signaling and its impact on myelinating glial cell differentiation, a fundamental knowledge that is currently lacking in the field. There are two types of specialized myelin-forming glial cells: Schwann cells (SC) in the PNS, and oligodendrocytes (OL) in the CNS. We have found that a cytoskeletal protein: non-muscle myosin II (NMII) regulates the development of myelinating glial cells. NMII inhibition impairs myelin formation in the PNS, but enhances CNS myelination. Our laboratory uses in vitro and in vivo models to elucidate the mechanisms behind these observations. The long-term goal of our research is to apply this knowledge to help the development of novel therapeutic tools to treat human demyelinating diseases.
Urbanski, M; Kingsbury, L; Moussouros, D; Kassim, I; Mehjabeen, S; Paknejad, N; Melendez-Vasquez, C.V (2016) Myelinating glia differentiation is regulated by extracellular matrix elasticity. Sci Rep. Sep 20; 6:33751. doi: 10.1038/srep33751.
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, A, Tewari, A., Einhenber, Steve Melendez-Vasquez C Myosin IIB is a negative regulator of oligodendrocyte differentiation (2012). J Neurosci Res 90:1547-1556. PMID: 22437915
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. PMID: 21864535.
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).