Cancer is driven by cells that proliferate more than normal and migrate into places where they do not belong. To limit the spreading, and to keep the disease local, we are focusing on the fundamental mechanics of cell migration.
We seek to limit cell migration by using an integrated mathematical-computational modeling and live cell imaging approach, using quantitative biophysical measurements to constrain our models. We are particularly focused on how cells interpret the mechanics, chemistry, and architecture of their environment, and use microfabrication, mouse models, and freshly resected human tumor tissue in our experiments.
Our modeling uses fundamental physical and chemical principles to predict, and ultimately control, cell migration behavior in complex environments. We are now building a next-generation cell migration simulator, as well as a tumor simulator to predict longer time and length scale dynamics.
Microtubule and tau dynamics in Alzheimer's disease
The positioning of intracellular structures is determined largely by the organization of the cytoskeleton, a collection of self-assembled protein filaments inside eukaryotic cells that serve as nanometer-scale railroad tracks for molecular motors and their associated cargoes.
A prime example is the movement of transport vesicles during neuron growth, regeneration, and maintenance. Microtubules then undergo stochastic switching between rounds of assembly and disassembly, which allows neurons to remodel their synaptic connections during learning and degeneration.
My laboratory is interested in modeling the kinetics and thermodynamics of microtubule assembly and disassembly, and the dynamics of the microtubule-associated protein tau, which aggregates in neurodegenerative diseases, such as Alzheimer’s disease.
Through our fundamental biophysical investigations that integrate modeling and experimental approaches at the atomistic, molecular, and cellular levels, we aim to better understand and limit the degeneration that occurs in Alzheimer’s disease.
D.J. Odde, “Shifting the optimal stiffness for cell migration,” Nature Communications, 8:15313 (2017).
Tubman, E.S., S. Biggins, and D.J. Odde, "Model for spindle-attachment error correction in budding yeast mitosis," Cell Systems, in press.
Mekhdjian, A.H.*, F.B. Kai*, M.G. Rubashkin*, L.S. Prahl, L.M. Przybyla, A.L. McGregor, E.S. Bell, M.J. Barnes, C.C. DuFort, G. Ou, A.C. Chang, L. Cassereau, S.J. Tan, M.W. Pickup, J.N. Lakins, X. Ye, M.W. Davidson, J. Lammerding, D.J. Odde, A.R. Dunn, V.M. Weaver, “Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix,” Molecular Biology of the Cell, 28(11):1467-1488 (2017) *These authors contributed equally.
Castle, B.T., McCubbin, S., Prahl, L.S., Bernens, J.N., Sept, D., and D.J. Odde, (2017), “Mechanisms of kinetic stabilization by the drugs paclitaxel and vinblastine,” Molecular Biology of the Cell, 28:9 1238-1257.
Marko, T.A., Shamsan, G.A., Edwards, E.N., Hazelton, P.E., Rathe, S.K., Cornax, I., Overn, P.R., Varshney, J., Diessner, B.J., Moriarity, B.S., O'Sullivan, M.G., Odde, D.J., and Largaespada, D.A. (2016). Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma. Scientific Reports, 6, 39059.
Castle, B.T. and D.J. Odde, “Optical Control of Microtubule Dynamics in Time and Space,” Cell, 162(2): p. 243-5 (2015).
Odde, D.J., “Mitosis, diffusible crosslinkers, and the ideal gas law,” Cell, 160(6): p. 1041-3 (2015).
Castle, B.T. and D.J. Odde, “Brownian dynamics of subunit addition-loss kinetics and thermodynamics in linear polymer self-assembly,” Biophysical Journal, 105:2528-2540 (2013).
Bangasser, B.L. and D.J. Odde, “Master Equation-Based Analysis of a Motor-Clutch Model for Cell Traction Force,” Cellular and Molecular Bioengineering, 6:449-459 (2013).
Bangasser, B.L., S.S. Rosenfeld, and D.J. Odde, “Determinants of maximal force transmission in a motor-clutch model of cell traction in a compliant microenvironment,” Biophysical Journal, 105(3): p. 581-92 (2013).
Flink C, and D.J. Odde, “Science+dance=bodystorming,” Trends in Cell Biology, 22:613-616 (2012).
Odde, D.J., “Getting cells and tissues into shape,” Cell, 144, 325-326 (2011).
Griffin, E.E., D.J. Odde, G. Seydoux, "Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle," Cell, 146, 955-68 (2011).
Chan, C.E. and D.J. Odde, “Traction dynamics of filopodia on compliant substrates,” Science, 2008. 322(5908): p. 1687-91.
Gardner, M.K. and D.J. Odde, “Dam1 goes it alone on disassembling microtubules,” Nature Cell Biology, 10, 379-381 (2008).
Gardner, M.K., D.C. Bouck, L.V. Paliulis, J.B. Meehl, E.T. O'Toole, J. Haase, A. Soubry, A.P. Joglekar, M. Winey, E.D. Salmon, K. Bloom, and D.J. Odde, “Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules,” Cell, 2008. 135(5): p. 894-906.
Nahmias Y. and D.J. Odde, “Micropatterning of hepatic-endothelial sinusoid-like structures by laser-guided direct writing,” Nature Protocols, 1, 2288-2296 (2006).