Stuart Feinstein

Biography

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. In 2017, he received the Chancellor’s Award for Excellence in Undergraduate Research Award. Dr. Feinstein is presently Co-Director of the Neuroscience Research Institute.

Research

Our investigations focus upon the normal and pathological action of the microtubule (MT) associated protein, tau. Normally, tau controls MT growing and shortening, thereby regulating the many essential functions performed by MTs such as axonal transport. Alternatively, tau dysfunction has long been associated with Alzheimer's and related dementias. Genetic analyses have demonstrated that mutations affecting either tau structure or regulation of its action can cause neuronal cell death and dementia.

Our efforts to understand normal and pathological tau action employ protein biochemistry, molecular cell biology and biophysics. Many of these efforts are collaborative with colleagues here at UCSB. We seek to understand precise mechanistic details by which tau regulates MT 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 (i) promoting MT bundling in axons, (ii) the roles of tau oligomerization and fragmentation in normal and pathological tau action, (iii) mechanisms underlying pathological tau aggregation and (iv) tau action at MT ends.

Selected Publications

Wozniak, K.M. Vornov, J.J. Wu, Y., Liu, Y., Carozzi, V., Fumagalli, G., Alberti, P., Cook, B., Wilson, L., Jordan, M.A., Feinstein, S.C., Littlefield, B.A., Nomoto, K., Condon, K., Eckley, S. Desjardins, C., Cavaletti, G., Polydefkis, M. and Slusher, B.S. (2018) Peripheral neuropathy induced by microtubule-targeted chemotherapies: insights into acute injury and long-term recovery. Cancer Research

Benbow, S.J., Wozkiak, K.M., Kulesh, B., Savage, A., Slusher, B.S., Littlefield, B.A., Jordan, M.A., Wilson, L. and Feinstein, S.C. (2017) Microtubule Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy Induced Peripheral Neuropathy. Neurotoxicology Research. 32:151-162.

Smith, J.A, Slusher, B.S., Wozniak, K., Farah, M.H., Smiyun, G., Wilson, L., Feinstein, S.C. and Jordan, M.A. (2016) Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting Cancer Drugs. Cancer Research 76(17):5115-5123.

Chung, P.J., Song, C., Deek, J., Miller H.P., Li Y., Choi , M.C., Wilson L., Feinstein, S.C. and Safinya, C.R. (2016) Tau Mediates Microtubule Bundle Architectures Mimicking Fascicles of Microtubules found in the Axon Initial Segment. Nature Communications 7:12278.

Feinstein, H.E., Benbow, S.J., LaPointe, N.E., Patel, N., Ramachandran, S., Do, T., Gaylord, M.R., Huskey, N.E., Dressler, N., Korff, M., Quon, B. Lazar Cantrell, K., Bowers, M.T., Lal, R. and Feinstein, S.C. (2016) Oligomerization of the Microtubule Associated Protein Tau is Mediated by its N-Terminal Sequences: Implications for Normal and Pathological Tau Action. Journal of Neurochemistry 137:939-954.

Benbow, S.J., Cook, B.M., Reifert, J., Wozkiak, K.M., Slusher, B.S., Littlefield, B.A., Wilson, L., Jordan, M.A. and Feinstein, S.C. (2015) Distinct Morphological and Molecular Responses to Paclitaxel and Eribulin Administration in Mouse Sciatic Nerve: a Microtubule Based Rationale for Differential Induction of Chemotherapy-Induced Peripheral Neuropathy. Neurotoxicology Research 29(2):299-313.

Chung, P.J., Choi, M.C., Miller, H.P., Feinstein, H.E., Raviv, U., Li, Y., Wilson, L., Feinstein, S.C. and Safinya, C.R. (2015) Direct force measurements reveal microtubule-associated-protein tau confers short-range attractions and isoform dependent steric stabilization to microtubules. Proc. Natl. Acad. Sci. USA (112(47):E6416-25. doi: 10.1073/)

Levine, Z.A., Larini, L., LaPointe, N.E., Feinstein, S.C. and Shea, J.-E. (2015) Regulation and Aggregation of Intrinsically Disordered Peptides. Proceedings of the National Academy of Sciences USA 112:2758-2763.

Larini, L., Gessel, M.M., LaPointe, N.E., Do, T.D., Bowers, M.T., Feinstein, S.C. and Shea, J.E. (2013) Initiation of assembly of tau(273-284) and its ΔK280 mutant: an experimental and computational study. Phys Chem Chem Phys. 15(23):8916-8928.

LaPointe, N.E., Morfini, G., Brady, S.T., Feinstein, S. C., Wilson, L., and Jordan, M.A.. (2013) Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: Implications for chemotherapy-induced peripheral neuropathy. Journal of Neurotoxicology 37:231-239.

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).

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.

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.

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

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., 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.

Panda, D. Goode, B.L., Feinstein, S.C. and Wilson, L. (1995) Kinetic Stabilization of Microtubule Dynamics at Steady State by Tau and Microtubule Binding Domains of Tau. Biochemistry 34:11117-11127.

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.

Drubin, D.G., Feinstein, S.C., Shooter, E.M. and Kirschner, M.W. (1985) Nerve Growth Factor Induced Neurite Outgrowth in PC12 Cells Involves Microtubule Assembly and Induction of Microtubule Assembly Promoting Factors. Journal of Cell Biology 101:1799-1807.