Director, Molecular and Cellular Pharmacology Graduate Program
Ph.D., 1999 Rutgers University , Piscataway NJ
Post-doctoral work, University of Cambridge , Cambridge U.K.
Research in the Colognato Lab focuses on investigating the molecular mechanisms that control the development and function of oligodendroglia. Oligodendroglia are specialized glial cells that are crucial for neural networks in the brain and spinal cord to operate at maximum speed and efficiency. The lab has been uncovering how developing oligodendroglia interact with extracellular matrix proteins, both in their germinal niche as they transition from neural stem cells to specialized glia, as well as in the developing nerve tracts themselves, where final maturation and functional integration takes place. Also, several projects study the reparative ability of oligodendroglia in the adult brain, as the specialized myelin membranes that oligodendroglia produce are damaged and/or dysfunctional in many neurodegenerative conditions, including Multiple Sclerosis.
We study a specialized glial cell, the oligodendrocyte, which myelinates axons in the brain and spinal cord. The laminin family of adhesion proteins are good candidates to regulate oligodendrocytes and the process of myelination: brain defects, including abnormal myelination, occur in the absence of normal laminin signaling. Our work has demonstrated that adhesive interactions with laminins can stimulate oligodendrocytes to survive and differentiate, at least in part by altering interactions with growth factors and downstream signal transduction mechanisms. We are now learning how laminins and laminin-regulated signaling molecules operate during normal brain development and function, as well as during diseases where myelination is dysregulated. An understanding of the mechanisms that control myelination will be important for two areas of human health: (1) during development, where normal myelination is crucial, and (2), during brain and spinal cord repair, which is hampered by the inability of the central nervous system (CNS) to regenerate. Remyelination failure leads to the neurodegeneration in demyelinating diseases such as Multiple Sclerosis, and is predicted to play a role in the neurodegeneration process in diseases such as Alzheimer's, and, following CNS injury in which new neuronal connections need to be myelinated to achieve functional recovery. One of our long-term objectives is to design pharmacological strategies to enhance myelination and myelin repair in the damaged nervous system.
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Colognato, H., Baron, W., Avellana-Adalid, V., Relvas, J., Baron-van Evercooren, A., Georges-Labouesse, E., and ffrench-Constant,C. (2002) CNS integrins switch growth factor signaling to promote target-dependent survival. Nat. Cell Biol. 4(11):833-841.
Baron,W., Decker,L., Colognato,H., and ffrench-Constant,C. (2003) Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains. Curr. Biol. 13(2):151-155.
Colognato, H., and ffrench-Constant, C. (2004) Mechanisms of glial development. Curr. Opin. in Neurobiol. 14:37-44. *corresponding author*
ffrench-Constant, C., Colognato, H., and Franklin, R.J.M. (2004) The Mysteries of Myelin Unwrapped. Science. 304(5671):688-9
*Colognato, H., Ramachandrappa, S., Olsen, I.M., and ffrench-Constant, C. Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. (2004) J. Cell Biol. 162(2):365-375. *corresponding author
ffrench-Constant, C. and Colognato, H. Integrins: versatile integrators of extracellular signals. (2004) Trends in Cell Biol. 14(12):678-686.
Baron W, Colognato H, ffrench-Constant C. (2005) Integrin-growth factor interactions as regulators of oligodendroglial development and function. Glia. 49(4):467-79.
Colognato, H., ffrench-Constant, C., and Feltri, M.L. (2005) Human diseases reveal novel roles for neural laminins. Trends Neurosci. (9):480-6..
Benninger, Y., Colognato, H., Thurnherr, T., Franklin, R., Leone, D., Atanasoski, S., Nave, K.-A., ffrench-Constant, C., Suter, U., and Relvas, J. (2006) b1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for central nervous system myelination and remyelination. J. Neurosci. 26(29):7665-73.
Wang, Z., Colognato, H., ffrench-Constant, C. (2007) Contrasting effects of mitogenic growth factors on myelination in neuron- oligodendrocyte co-cultures. Glia 55(5):537-45
*Colognato, H., Galvin, J., Wang, Z., Relucio, J., Nguyen, T., Harrison, D., Yurchenco, P., and ffrench-Constant, C. Identification of dystroglycan as a second laminin receptor in oligodendrocytes with a role in myelination. (2007) Development 134(9):1723-36. *corresponding author
Barros, C.S.#, Nguyen, T.#, Spencer, K.S.R., Colognato, H.*, and Mueller, U.* b1-integrins are required for normal CNS myelination and promote Akt-dependent myelin outgrowth. (2009)Development 136(16):2717-2724. *co-corresponding authors, #equal contributions
Loulier, K., Lathia, J.D., Marthiens, V., Relucio, J., Mughal, M.R., Tang, S.-C., Coksaygan, T., Hall, P.E., Chigurupati, S., Patton, B., Colognato, H., Rao, M.S., Mattson, M.P., Haydar, T.F., and ffrench-Constant, C. b1-integrin maintains integrity of the embryonic neocortical stem cell niche. (2009) PLoS Biology 7(8)e1000176.
Relucio, J., Tzvetanova, I.D., Ao, W., Lindquist, S., and Colognato, H. Laminin alters Fyn regulatory mechanisms and promotes oligodendrocyte development. (2009) J. Neurosci. 29(38):11794-11806.
Kuo, R.-S. #, Park, D. #, Tzvetanova, I.D., Leiton, C., Cho, B., and Colognato, H. Tyrosine phosphatases Shp-1 and Shp-2 perform unique and opposing roles during oligodendrocyte development. (2010) J. Neurochemistry, 113:210-212. #equal contributions.
Galvin, J., Eyermann, C., and Colognato, H. Dystroglycan modulates insulin-like growth factor signaling to promote oligodendrocyte differentiation. (2010) J. Neurosci. Res. 88(15):3295-307
Colognato, H. and Tzvetanova, I.D. Glia unglued: How signals from the extracellular matrix regulate the development of myelinating glia. Dev. Neurobiology special issue entitled “The role of extracellular matrix in nervous system development and maintenance.” In press.
The Colognato Lab studies the development and function of glial cells, in particular oligodendroglia and astrocytes, which are specialized neural cells found in the brain and spinal cord. Several projects in the lab focus on the role of adhesion receptors and extracellular matrix proteins as regulatory factors in the genesis, development, and function of oligodendroglia, which are born in a specialized stem cell niche in the developing perinatal brain. Additional projects focus on the role of adult oligodendroglia in repair following damage to nerve tracts, as well as on the role of astrocyte extracellular matrix proteins that influence the development and function of the blood-brain barrier.
Chris Eyermann – Pharmacology Graduate Student – investigating the role of the adhesion receptor, dystroglycan, in modulating oligodendroglial cytoskeletal process dynamics during myelination.
Freyja McClenahan – Program in Neurosciences Graduate Student – investigating how the adhesion receptor dystroglycan interacts with extracellular matrix proteins in a neural stem cell niche to influence gliogenesis during early postnatal brain development.
Cindy Leiton – Pharmacology Graduate Student – investigating the ability of matrix metalloproteinases to modulate oligodendroglial differentiation and myelination capacity by virtue of their ability to remodel cell interactions with extracellular matrix proteins
Mike Menezes – Physiology and Biophysics Graduate Student – investigating the role of the astrocytic extracellular matrix protein laminin in the development and function of the blood-brain barrier.