The focus of our laboratory is on the role of molecular motors in driving the malignant phenotype of glioblastoma. We are currently working on three projects:
In the first, we are examining how myosins IIA and IIB enable glioma cells to maneuver through the small intercellular spaces found in brain white matter and cortex, and tune glioma responsiveness to the stiffness of the microenvironment in which they migrate and grow. Hand-in-hand with these studies are experiments examining the efficacy of myosin II-targeting therapeutics administered in rodent models of glioma.
In the second project, we are examining how myosins Vb and VI are needed to sensitize glioma cells to extracellular growth factors, including PDGF and EGF. We are investigating how suppression of these motors affects tumor dispersion and growth in pre-clinical models of glioma.
The third involves a collaboration with Dr. Jeremy Rich, and is examining the role of mitotic kinesins in supporting proliferation in glioma stem cells. My laboratory has pioneered in the development of new structure/function assays that we have successfully used to probe the enzymatic mechanisms of these kinesins, and we are currently applying these in pharmaceutical studies.
Yardimci H. van Duffelen M. Mao Y. Rosenfeld SS. Selvin PR. (2008) Proc. Nat. Acad. Sci. USA. 105, 6016-6021.
Beadle C. Assanah MC. Monzo P. Vallee R. Rosenfeld SS. Canoll P. (2008) Molecular Biology of the Cell. 19, 3357-3368.
Erdal Toprak, Ahmet Yildiz, Melinda Tonks Hoffman, Steven S. Rosenfeld, and Paul R. Selvin (2009) PNAS,106, 2717-12722.
Rosenfeld SS. et al. (2009). Journal of Biological Chemistry. 284, 32858-68..
Adeline Goulet, Steven S. Rosenfeld, and Carolyn A. Moores J. Biol. Chem. 2012 287: 44654-4466.
Sanja Ivkovic, Steven S. Rosenfeld et al. Mol. Biol. Cell 2012 23:4 533-542.
Adeline Goulet, Steven S. Rosenfeld, et al.. J. Biol. Chem. 287: 44654-44666, 2012.
Bengasser, B.L., Rosenfeld, SS, and Odde, D.J. (2013) “Determinants of maximal force transmission in a motor-clutch model of cell traction in a compliant microenvironment”. Biophysical Journal, in press, PMC Journal--in press
Lerner Research Institute
Mail Code NB21
9500 Euclid Avenue
Cleveland, Ohio 44195