Search Results to William J. Lehman, PhD

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Research Expertise & Professional Interests We are involved in structural studies on the assembly and function of actin-containing thin filaments in muscle and non-muscle cells. Our principal goal is to analyze and elucidate the mechanisms of thin filament-linked regulation of muscle contraction and cytoskeletal remodeling. To accomplish this goal, we use a combination of molecular biology, electron microscopy, electron tomography, image reconstruction and molecular dynamics protocols to better understand the interactions and dynamics of protein components of isolated and reconstituted thin filaments. Studies on mutants are carried out to better understand abnormal filament function in disease processes. We have an excellent track record in successfully educating graduate and post-doctoral students in the application of the state-of-the-art techniques that we use. In particular, we have trained students with backgrounds in biological and biochemical sciences (my own experience) to be fearless about the challenge of carrying out sophisticated biophysical approaches, and, conversely, teaching students with background in physical and computational sciences to understand the biomedical underpinnings of our work. This dual process of training students with these diverse backgrounds in one laboratory setting is synergistic. As a sign of our success, of the 19 papers that have been published by us since 2007, 12 were co-authored by 5 different post-doctoral fellows and by 3 graduate students from my laboratory. Our laboratory was the first to directly visualize the steric-blocking mechanism of muscle regulation by identifying the positions assumed by tropomyosin on actin in the presence and the absence of Ca2+ using cryo-electron microscopy and negative staining. We also have demonstrated that during muscle activation tropomyosin moves away from myosin cross-bridge binding sites on actin in two highly cooperative steps, one induced by Ca2+ binding to troponin and a second induced by the binding of myosin to actin. Our laboratory is continuing the above-mentioned studies to obtain even greater resolution of the processes involved. At the same time, we are investigating the structural organization of troponin on thin filaments and the changes it undergoes on binding of Ca2+. We are also engaged in studies on the structural interactions of other actin binding proteins including a-actinin, caldesmon, calponin, cortactin, filamin and native and mutant dystrophin, namely proteins that play important roles in the organization of the cytoskeleton in striated and smooth muscles as well as in non-muscle cells.
Self-Described Keywords Electron Microscopy

One or more keywords matched the following items that are connected to Lehman, William

Item TypeName
Concept Microscopy, Electron
Concept Microscopy, Electron, Transmission
Academic Article Steric-blocking by tropomyosin visualized in relaxed vertebrate muscle thin filaments.
Academic Article Three-dimensional reconstruction of caldesmon-containing smooth muscle thin filaments.
Academic Article Steric-model for activation of muscle thin filaments.
Academic Article Three-dimensional image reconstruction of reconstituted smooth muscle thin filaments: effects of caldesmon.
Academic Article Visualization of caldesmon on smooth muscle thin filaments.
Academic Article 3-D image reconstruction of reconstituted smooth muscle thin filaments containing calponin: visualization of interactions between F-actin and calponin.
Academic Article Three-dimensional reconstruction of thin filaments containing mutant tropomyosin.
Academic Article Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments.
Academic Article Effects of a cardiomyopathy-causing troponin t mutation on thin filament function and structure.
Academic Article Troponin organization on relaxed and activated thin filaments revealed by electron microscopy and three-dimensional reconstruction.
Academic Article Myosin light chain kinase binding to a unique site on F-actin revealed by three-dimensional image reconstruction.
Academic Article Crossbridge and tropomyosin positions observed in native, interacting thick and thin filaments.
Academic Article An atomic model for actin binding by the CH domains and spectrin-repeat modules of utrophin and dystrophin.
Academic Article Drosophila muscle regulation characterized by electron microscopy and three-dimensional reconstruction of thin filament mutants.
Academic Article Modes of caldesmon binding to actin: sites of caldesmon contact and modulation of interactions by phosphorylation.
Academic Article Single particle analysis of relaxed and activated muscle thin filaments.
Academic Article Mini-thin filaments regulated by troponin-tropomyosin.
Academic Article E93K charge reversal on actin perturbs steric regulation of thin filaments.
Academic Article Cortactin binding to F-actin revealed by electron microscopy and 3D reconstruction.
Academic Article A comparison of muscle thin filament models obtained from electron microscopy reconstructions and low-angle X-ray fibre diagrams from non-overlap muscle.
Academic Article Acetylation regulates tropomyosin function in the fission yeast Schizosaccharomyces pombe.
Academic Article Structural basis for the regulation of muscle contraction by troponin and tropomyosin.
Academic Article Caldesmon and the structure of smooth muscle thin filaments: electron microscopy of isolated thin filaments.
Academic Article The shape and flexibility of tropomyosin coiled coils: implications for actin filament assembly and regulation.
Academic Article Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities.
Academic Article The C terminus of cardiac troponin I stabilizes the Ca2+-activated state of tropomyosin on actin filaments.
Academic Article Electron microscopy and persistence length analysis of semi-rigid smooth muscle tropomyosin strands.
Academic Article Tropomyosin position on F-actin revealed by EM reconstruction and computational chemistry.
Academic Article Electron microscopy and 3D reconstruction of F-actin decorated with cardiac myosin-binding protein C (cMyBP-C).
Academic Article Effects of basic calponin on the flexural mechanics and stability of F-actin.
Academic Article The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy.
Academic Article Electron microscopy and 3D reconstruction reveals filamin Ig domain binding to F-actin.
Academic Article The effect of calcium on the aggregation of chicken gizzard thin filaments.
Academic Article The location and periodicity of a troponin-T-like protein in the myofibril of the horseshoe crab Limulus polyphemus.
Academic Article The structural elements responsible for contraction in the ciliate Spirostomum.
Academic Article Ca(2+)-induced tropomyosin movement in Limulus thin filaments revealed by three-dimensional reconstruction.
Academic Article A Drosophila melanogaster model of diastolic dysfunction and cardiomyopathy based on impaired troponin-T function.
Academic Article Tropomyosin Flexibility Evaluated by Electron Microscopy Image Analysis
Academic Article Electron Microscopy and Molecular Dynamics on a D137L Mutant of Tropomyosin

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  • Electron microscopy