Michael L. Shelanski, M.D., Ph.D.

We are currently using a combination of cell biological and molecular biological approaches, including anti-sense technology, to study the function of two proteins - the intermediate filament peripherin and the high molecular weight form of the microtubule associated protein tau - which are characteristic of the cytoskeleton of the peripheral neuron. We are specifically interested in why there are differences between the central and peripheral cytoskeleton and whether these differences are related to the greater regenerative potential of peripheral neurons. To aid in this effort we have set up a model "axon" using baculovirus expression and insect SF9 cells to assess interactions between specific cytoskeletal components.

A related series of studies is investigating the mechanism by which astrocytes and neurons initiate the formation of long asymmetric processes. Our approach has shown that process formation in the astrocyte is inhibited by the cortical actin network and favored by the assembly of microtubules. This equilibrium is controlled by the myosin light chain kinase acting on the myosin light chain and on destrin - an actin severing protein. These studies utilize a variety of cell biology approaches including biochemistry, EM, optical imaging and antisense oligonucleotides. Other research in the laboratory is on the role of cytokines, specifically IL 1 on the development of cytoskeletal changes in Alzheimer s disease.

Selected Publications:

• Troy, C.M.., Greene, L.A. and Shelanski, M.L.(1992). Neurite outgrowth in peripherin-depleted PC12 cells. J.Cell Biol. 117:1085-1092.
• Georgieff, I.S., Liem,R.K.H., Couchie, D., Mavilia, C., Nunez, J. and Shelanski, M.L. (1993). Expression of high molecular weight tau in the central and peripheral nervous systems. J. Cell Sci. 105:729-737.
• Teng, K.K., Georgieff, I.S., Aletta, J.M., Nunez, J., Shelanski, M.L., (1993). Characterization of a PC12 cell subclone (PC12-C41) with enhanced neurite outgrowth capacity: Implications for a modulatory role of high molecular weight tau in neuritogenesis. J.Cell Sci. 106:611-626.
• Shelanski, M.L., Frappier, T., Georgiefff, I.S., Troy, C.M. and Mellado, W. (1995). Cytoskeletons of central and Peripheral Neurons (In press).
• Hendey, N., Troy, C.M., Maxfield, F. and Shelanski, M.L.(1995). Motility in vitrnectin is impaird in neutrophils from patients with Alzheimer s Disease. Neurobio. of Aging (submitted).
• Troy, C.M. and Shelanski, M.L. (1995). Down-regulation of copper/zinc superoxide dismutase (SOD1) causes apoptotic cell death in PC12 neuronal cells. Proc. Nat. Acad. Sci. (U.S.A.). 91:6384-6387.