Regulation of cytoskeletal dynamics and cell motility.
Ph.D., Cleveland State University
The broad goal of my research at UNCG is to gain further insight into how cells are able to achieve highly coordinated changes in shape that are required for critical cellular processes such as chemotaxis, cytokinesis, intracellular trafficking, and multicellular development. To this end, I use the social amoeba, Dictyostelium discoideum, as a model system for examining the molecular pathways regulating the ability of myosin II to mediate contraction of actin filaments in the highly dynamic context of a nonmuscle cell. More specifically, we have focused much of our attention on identifying factors that regulate the activity of an enzyme called myosin heavy chain kinase A (MHCK-A). MHCK-A plays a central role in regulating Dictyostelium cellular contraction by catalyzing the disassembly of myosin II filaments; the functional consequence of filament disassembly is the inactivation of myosin II-mediated contraction of the cell. The long term goal of my research program is to provide a clearer understanding of the molecular events driving cellular contractile processes since defects in the regulation of these events, as occur in cancer cells, can lead to uncontrolled cell multiplication (tumor formation) and unregulated cell migration observed with metastasis.
Wessels D, Lusche DF, Steimle PA, Scherer A, Kuhl S, Wood K, Hanson B, Egelhoff TT, Soll DR. Myosin heavy chain kinases play essential roles in Ca2+, but not cAMP, chemotaxis and the natural aggregation of Dictyostelium discoideum. (2012) Journal of Cell Science. 125(Pt 20):4934-44.
Wang Y., Steimle P.A., Ren Y., Ross C.A., Robinson D.N., Egelhoff T.T., Sesaki H., Iijima M. Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation. (2011) MBoC. 22(13):2270-2281.
Underwood J, Greene J, Steimle PA. Identification of a new mechanism for targeting myosin II heavy chain phosphorylation by Dictyostelium myosin heavy chain kinase B. (2010) BMC Res Notes 3(1):56.
Franklin A, Hyatt L, Chowdhury A, Steimle PA. WD repeat domain of Dictyostelium myosin heavy chain kinase C functions in both substrate targeting and cellular localization. (2010) Eukaryot Cell. 9(2):344-9.
Mondal S, Bakthavatsalam D, Steimle P, Gassen B, Rivero F, Noegel AA. Linking Ras to myosin function: RasGEF Q, a Dictyostelium exchange factor for RasB, affects myosin II functions. (2008) Journal of Cell Biology. 181(5):747-60.
Russ, M., Martinez R., Ali H., Steimle P.A.; Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration. (2006) Biochemical and Biophysical Research Communications. 345(1):516-22.
Russ, M., Croft, D., Ali, O., Martinez, R. and Steimle, P.A. (2005) Myosin heavy chain kinase A from Dictyostelium possesses a novel actin binding domain that cross-links actin filaments. Biochemical Journal. 395(2):373-83
Steimle, P.A., Fulcher, F.K., and Patel, Y.M. (2005) A novel role for myosin II in insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications. 331(4):1560-1565.
Egelhoff T.T., Croft D., Steimle P.A. (2005) Actin-activation of myosin heavy chain kinase A in Dictyostelium: A biochemical mechanism for the spatial regulation of myosin II filament disassembly. Journal of Biological Chemistry. 280(4): 2879-2887.
Principles of Biology I (BIO 111)
Cell Biology Lab (BIO 356)
Introduction to Biotechnology (BIO 494)
Molecular Biological Approaches in Research (BIO 596)