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Stuart Feinstein

Professor

Contact Information

Phone: (805) 893-2659
Email: feinstei@lifesci.ucsb.edu
Office: 5123A Bio II
Website: Feinstein Lab

Address

Molecular, Cellular, and Developmental Biology
University of California, Santa Barbara
Santa Barbara, CA 93106-9625

Bio

Dr. Feinstein earned his undergraduate degree in Biochemistry at the University of California, Berkeley and his Ph.D. from the Department of Biochemistry and Biophysics at the University of California School of Medicine, San Francisco. Subsequently, he was a postdoctoral fellow in the Department of Neurobiology at the Stanford University School of Medicine until 1986, at which time he joined the faculty at UCSB. He has served as a grant reviewer for the National Institutes of Health, the National Science Foundation and the Cancer Research Coordinating Committee of California. In 2011, he was appointed a National Academies Education Fellow in the Life Sciences by the National Academies of Science and previously has been awarded a UCSB Distinguished Teaching Award. Dr. Feinstein is presently Co-Director of the Neuroscience Research Institute.

Research

Beginning with a long-standing interest in molecular mechanisms underlying the normal development and maintenance of the nervous system, our work has evolved to include a major effort to understand neurodegenerative diseases such as Alzheimer's, FTDP-17 and Progressive Supranuclear Palsy. Our investigations focus upon the normal and pathological action of the microtubule associated protein, tau. Normally, this tightly regulated protein controls microtubule growing and shortening, thereby regulating the numerous essential functions performed by microtubules such as axonal transport. On the other hand, tau dysfunction has long been associated with Alzheimer’s disease and related dementias. Recent genetic analyses have demonstrated that mutations affecting either the primary structure or tau, or regulation of its action, can cause neuronal cell death and dementia. Unfortunately, the underlying molecular mechanisms by which tau destroys neurons remains very poorly understood.

Our efforts to understand normal and pathological tau action employ a wide range of strategies and technologies, including protein biochemistry, molecular cell biology, biophysics and bioengineering. Many of these efforts are collaborative with colleagues here at UCSB and elsewhere. We seek to understand precise mechanistic details by which tau regulates microtubule behavior and neuronal cell biology, integrating high resolution in vitro biochemical and biophysical analyses with investigations in cells. Among our most recent efforts are analyses examining the roles of tau in axonal transport under normal and pathological conditions, the possible roles of tau fragmentation in the onset of disease, the possible role of tau oligomerization in normal and pathological tau action and the combinatorial effects of multiple phosphorylation upon the regulation of tau action. Together with our many collaborators, we hope to gain a more complete understanding of normal neuronal development and maintenance as well as what goes wrong in neurodegenerative disease.

Selected Publications

  • Reifert, J., Hartung-Cranston, D.A. and Feinstein, S.C. (2011) Amyloid beta mediated cell death of cultured hippocampal neurons reveals extensive tau fragmentation without increased full-length tau phosphorylation . Journal of Biological Chemistry 286:20797-20811.
  • Safinya, C.R., Raviv, U., Needleman, D.J., Zidovska, A., Choi, M.C., Ojeda-Lopez, M.A., Ewert, K.K., Li, Y., Miller, H.P., Quispe, J., Carragher, B., Potter, C.S., Kim, M.W., Feinstein, S.C. and Wilson, L. (2011) Nanoscale Assembly in Biological Systems: From Neuronal Cytoskeletal Proteins to Curvature Stabilizing Lipids. Advanced Materials 23:2260-2270.
  • Kiris, E., Ventimiglia, D., Sargin, M., Gaylord, M., Altinok, A., Rose, K., Manjunath, B.S., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2011) Combinatorial Tau Pseudophosphorylation: Markedly Different Effects on Microtubule Assembly and Dynamic Instability than the Sum of the Individual Parts”. Journal of Biological Chemistry 286(16):14257-70).
  • Peck, A., Sargin, M.E., LaPointe, N.E., Rose, K., Manjunath, B.S., Feinstein, S.C. and Wilson, L. (2011) Tau Isoform Specific Modulation of Kinesin Driven Microtubule Gliding Rates and Trajectories as Determined with Tau-stabilized Microtubules. Cytoskeleton 68:44-55.
  • Choi, M.C., Raviv, U., Miller, H., Gaylord, M., Kiris, E., Ventimiglia, D., Needleman, D., Kim, M.W., Wilson, L., Feinstein, S.C. and Safinya, C.R. (2009) Human Microtubule Associated Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-ray Scattering Study. Biophysical Journal 97:519-527.
  • LeBoeuf, A., Levy, S., Gaylord, M., Bhattacharya, A., Singh, A., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2008) FTDP-17 Mutations in Tau Alter the Regulation of Microtubule Dynamics – An “Alternative Core” Model for Normal and Pathological Tau Action. Journal of Biological Chemistry 283:36406-36415
  • Rosenberg, K.J., Ross, J.L., Feinstein, E.H., Feinstein, S.C. and Israelachvilli, J. (2008) Complementary Dimerization of the Microtubule Associated Protein Tau: Implications for Microtubule Bundling and Tau Mediated Pathogenesis. Proceedings of the National Academy of Sciences USA 105:7445-50.
  • Bhattachara. A., Feinstein, S.C., LeBeouf, A., Levy, S., Singh,A. and Wilson, L. (2008) A General Modeling and Visualization Tool for Comparing Different Members of a Group: Application to Understanding Tau-Mediated Regulation of Microtubule Dynamics. BMC Bioinformatics 9:339.
  • Bunker, J., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2006) FTDP-17 Mutations Decrease The Ability Of Tau To Stabilize Microtubule Dynamics In Living Cells Journal of Biological Chemistry 281:11856-11863
  • Levy, S. , LeBeouf, A. Massie, M., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2005) Three- and Four-Repeat Tau Regulate the Dynamics of Two Distinct Microtubule Sub-populations in Qualitatively different manners: Implications for Neurodegeneration. Journal of Biological Chemistry 280:13520-13528
  • Feinstein, S.C. and Wilson, L. (2004) Inability of Tau to Properly Regulate Neuronal Microtubule Dynamics: A Loss-of-Function Mechanism by which Tau Might Mediate Neuronal Cell Death. BBA:Molecular Basis of Disease Vol 1739; Issues (2-3): 268-279.
  • Bunker, J., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2004) Modulation of Microtubule Dynamics by Tau in Living Cells: Implications for Development and Neurodegeneration. Molecular Biology of the Cell 15:2720-8272
  • Makrides, V., Massie, M., Feinstein, S.C. and Lew, J. (2004) Evidence for Two Distinct Binding Sites for Tau on Microtubules Proceedings of the National Academy of Sciences USA 101:6746-6751
  • Makrides, V., Shen, T.E., Bhatia, R., Smith, B.L., Thimm, J., Lal, R. and Feinstein, S.C. (2003) Microtubule Dependent Oligomerization of Tau: Implications for Physiological Tau Function and for Tauopathies. Journal of Biological Chemistry 278:33298-33304
  • Panda, D., Samuel, J.C., Massie, M., Feinstein, S.C. and Wilson, L. (2003) Differential Regulation of Microtubule Dynamics by 3-Repeat and 4-Repeat Tau: Implications for Normal Neuronal Development and the Onset of Neurodegenerative Disease. Proceedings of the National Academy of Sciences USA 100:9548-9553.
  • Goode, B.L., Chau, M., Denis, P.E. and Feinstein, S.C. (2000) Structural and Functional Differences Between 3-Repeat and 4-Repeat Tau Isoforms: Implications for Normal Tau Function and the Onset of Neurodegenerative Disease. Journal of Biological Chemistry 275:38182-38189.
  • Goode, B., Denis, P., Panda, D., Miller, H., Radeke, M.J., Wilson, L. and Feinstein, S.C. (1997) Functional Interactions between the Proline-rich and Repeat Regions of Tau Enhance Microtubule Binding and Assembly. Molecular Biology of the Cell 8:353-365.
  • Goode, B.L. and Feinstein, S.C., (1994) Identification of a Novel Microtubule Binding and Assembly Domain in the Developmentally Regulated, Inter-Repeat Region of Tau. Journal of Cell Biology 124:769-782.