Herb P. Miller
University of California, Santa Barbara
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Featured researches published by Herb P. Miller.
Biophysical Journal | 2009
Myung Chul Choi; Uri Raviv; Herb P. Miller; Michelle Gaylord; E. Kiris; D. Ventimiglia; Daniel J. Needleman; Mahn Won Kim; Les Wilson; Stuart C. Feinstein; Cyrus R. Safinya
Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from alphabeta heterodimeric tubulin. In neural cells, different isoforms of the microtubule-associated-protein (MAP) tau regulate tubulin assembly and MT stability. Using synchrotron small angle x-ray scattering (SAXS), we have examined the effects of all six naturally occurring central nervous system tau isoforms on the assembly structure of taxol-stabilized MTs. Most notably, we found that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius R(MT) of MTs with increasing Phi, the tau/tubulin-dimer molar ratio. Within experimental scatter, the change in R(MT) seems to be isoform independent. Significantly, R(MT) was observed to rapidly increase for 0 < Phi < 0.2 and saturate for Phi between 0.2-0.5. Thus, a local shape distortion of the tubulin dimer on tau binding, at coverages much less than a monolayer, is spread collectively over many dimers on the scale of protofilaments. This implies that tau regulates the shape of protofilaments and thus the spontaneous curvature C(o)(MT) of MTs leading to changes in the curvature C(MT) (=1/R(MT)). An important biological implication of these findings is a possible allosteric role for tau where the tau-induced shape changes of the MT surface may effect the MT binding activity of other MAPs present in neurons. Furthermore, the results, which provide insight into the regulation of the elastic properties of MTs by tau, may also impact biomaterials applications requiring radial size-controlled nanotubes.
Cancer Chemotherapy and Pharmacology | 2015
Manu Lopus; Greg Smiyun; Herb P. Miller; Emin Oroudjev; Leslie Wilson; Mary Ann Jordan
Ixabepilone (Ixempra, BMS-247550), a semisynthetic analog of epothilone B, is a microtubule-targeted drug in clinical use for treatment of metastatic or locally advanced breast cancer. Ixabepilone’s binding and mechanism of action on microtubules and their dynamics, as well as its interactions with isotypically altered microtubules, both in vitro and in tumor cells, have not been described. Microtubules are dynamic polymers of the protein tubulin that function in mitosis, intracellular transport, cell proliferation, and migration. They continually undergo dynamic instability, periods of slow growth and rapid shortening that are crucial to these cell functions. We determined ixabepilone’s microtubule binding and polymerization effects in vitro and also determined its effects on inhibition of dynamic instability in vitro and in cells, both with and without removal of the βIII isotype of tubulin. The βIII isotype of tubulin is associated with drug resistance and tumor aggressivity. We found that removal (in vitro) and knockdown (in cells) of βIII-tubulin led to increased inhibition of microtubule dynamic instability by ixabepilone. Depletion of βIII-tubulin from MCF7 human breast cancer cells also induced increased mitotic arrest by ixabepilone. Thus, βIII-tubulin expression suppresses the antitumor effects of ixabepilone, indicating that increased βIII-tubulin may be an important contributor to the development of resistance to ixabepilone.
Journal of Physics: Condensed Matter | 2005
Daniel J. Needleman; Jayna B. Jones; Uri Raviv; Miguel A. Ojeda-Lopez; Herb P. Miller; Youli Li; Les Wilson; Cyrus R. Safinya
With the completion of the human genome project, the biosciences community is beginning the daunting task of understanding the structures and functions of a large number of interacting biological macromolecules. Examples include the interacting molecules involved in the process of DNA condensation during the cell cycle, and in the formation of bundles and networks of filamentous actin proteins in cell attachment, motility and cytokinesis. In this proceedings paper we present examples of supramolecular assembly based on proteins derived from the vertebrate nerve cell cytoskeleton. The axonal cytoskeleton in vertebrate neurons provides a rich example of bundles and networks of neurofilaments, microtubules (MTs) and filamentous actin, where the nature of the interactions, structures, and structure–function correlations remains poorly understood. We describe synchrotron x-ray diffraction, electron microscopy, and optical imaging data, in reconstituted protein systems purified from bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories of polyelectrolyte bundling, including three-dimensional MT bundles and two-dimensional MT necklaces.
Langmuir | 2001
Thomas Pfohl; Joon Heon Kim; Mario Yasa; Herb P. Miller; Gerard C. L. Wong; Frank Bringezu; Zhiyu Wen; Les Wilson; Youli Li; Mahn Won Kim; Cyrus R. Safinya
Biophysical Journal | 2012
Peter J. Chung; Joanna Deek; Harrison E. Feinstein; Herb P. Miller; Myung Chul Choi; Leslie Wilson; Stuart C. Feinstein; Cyrus R. Safinya
Biophysical Journal | 2015
Peter J. Chung; Myung Chul Choi; Uri Raviv; Herb P. Miller; Les Wilson; Stuart C. Feinstein; Cyrus R. Safinya
Biophysical Journal | 2014
Peter J. Chung; Joanna Deek; Chae Yeon Song; Herb P. Miller; Myung Chul Choi; Leslie Wilson; Stuart C. Feinstein; Cyrus R. Safinya
Biophysical Journal | 2011
Myung Chul Choi; Peter J. Chung; Uri Raviv; Youli Li; Erkan Kiris; Herb P. Miller; Leslie Wilson; Stuart C. Feinstein; Cyrus R. Safinya
International Symposium on 'Future Trend in Soft Material Research with Advanced Light Source: Interdisciplinary of Bio- and Synthetic-Materials and Industrial Transferring' | 2010
Myung Chul Choi; Uri Raviv; Youli Li; Herb P. Miller; Daniel J. Needleman; Mahn Won Kim; Les Wilson; Stuart C. Feinstein; Cyrus R. Safinya
Bulletin of the American Physical Society | 2010
Myung Chul Choi; Uri Raviv; Herb P. Miller; Michelle Gaylord; Erkan Kiris; Donovan Ventimiglia; Daniel J. Needleman; P.J. Chung; J. Deek; N. LaPointe; Mincheol Kim; Leslie Wilson; Stuart C. Feinstein; Cyrus R. Safinya