Professional Appointments and Affiliations
Professor of Biomedical Engineering
Professor of Chemistry, courtesy appointment
BS, Biomedical Engineering, Duke University, 1988
Ph.D., Bioengineering, University of Washington, 1994
Cell and Molecular Bioengineering
Kinesin molecular motors, microtubules, molecular biomechanics, nanoscale biomolecular transport, directed assembly.
About the Hancock Lab
The Hancock lab is an interdisciplinary group spanning biophysics, biochemistry, cell biology and bioengineering. A major thrust in the lab is investigating the mechanochemical mechanism of biomolecular motors and how the motors kinesin and dynein carry out bidirectional transport of vesicles and organelles along intracellular microtubules. This transport is particularly important in neurons due to their highly elongated geometries, and defects in transport have been linked to neurodegenerative diseases. We use single-molecule microscopy to observe and track motor proteins, and by attaching gold nanoparticles motors as they step along microtubules, we have been able to quantify the kinetics of the transition rates between different mechanochemical states of the motors as they take 8 nm steps along the microtubule at ~100 steps/s. Using stopped-flow transient kinetics assays, we quantify the transition rates of ATP binding, hydrolysis, and product release that drive motor stepping. In other work, we are using microscopy and particle tracking to uncover the mechanism of microtubule polymerization, which is particularly important in dividing cells and is a target of a number of chemotherapy drugs. Using our single-molecule tracking tools, we are also investigating the mechanism by which cellulase enzymes breakdown cellulose, with the goal of lowering the cost barriers to efficient bioethanol production.
Honors and Awards
Dean's Fellow, College of Engineering, Pennsylvania State University, 2017
Selected Recent Publications
- Bidirectional cargo transport: moving beyond tug of war. W.O. Hancock. 2014. Nat Rev Mol Cell Biol. 15(9):615-28. PMID: 25118718
- The kinesin-1 chemomechanical cycle: stepping toward a consensus. 2016. W.O. Hancock. Biophys J, 110(6): 1216-1225. doi: 10.1016/j.bpj.2016.02.025. PMID: 27028632
- Kinetics of nucleotide-dependent structural transitions in the kinesin-1 hydrolysis cycle. 2015. K.J. Mickolajczyk, N.C. Deffenbaugh, J. Ortega Arroyo, J. Andrecka, P. Kukura, and W.O. Hancock. Proc. Natl. Acad. Sci., 112:E7186-7193. PMID: 26676576
- Microtubule binding kinetics of membrane-bound kinesin-1 predicts high motor copy numbers on intracellular cargo. Jiang, R., S. Vandal, S. Park, S. Majd, E. Tuzel and W.O. Hancock. 2019. Proc Natl Acad Sci U S A. 116(52): 26564-26570.
- A kinetic dissection of the fast and superprocessive kinesin-3 KIF1A reveals a predominate one-head-bound state during its chemomechanical cycle. T.M. Zaniewski, A.M. Gicking, J. Fricks, W.O. Hancock. 2020. J Biol Chem 295:17889-17903
- Kinesin-5 Promotes Microtubule Nucleation and Assembly by Stabilizing a Lattice-Competent Conformation of Tubulin. G.Y. Chen, J.M. Cleary, A.B. Asenjo, Y. Chen, J.A. Mascaro, D.F.J. Arginteanu, H. Sosa, and W.O. Hancock. 2019. Current Biology 29:2259-2269 e2254.
- Direct observation of individual tubulin dimers binding to growing microtubules. K.J. Mickolajczyk, E.A. Geyer, T. Kim, L.M. Rice, and W.O. Hancock. 2019. Proc Natl Acad Sci U S A 116:7314-7322.
- Nanoscale dynamics of cellulose digestion by the cellobiohydrolase TrCel7A. Z.K. Haviland, D. Nong, K.L.V. Kuntz, T.J. Starr, D. Ma, M. Tien, C.T. Anderson and W.O. Hancock. 2021. J. Biol. Chem. 297(3):101029.